Pearls and Pitfalls in Skin Ulcer Management [1st ed. 2023] 3031454529, 9783031454523

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Pearls and Pitfalls in Skin Ulcer Management [1st ed. 2023]
 3031454529, 9783031454523

Table of contents :
Part I: Introduction to Wound Care, Cleasing, Antiseptic and Local Treatment
1: Vulnology (Also Known as Wound Care): History and Myths of Chronic Wounds
2: Aetiology, Classification and Advocating for a Holistic, Multidisciplinary Approach
2.1 Epidemiology
2.2 Aetiopathogenesis
2.3 Classification
2.3.1 Venous Ulcers
2.3.2 Arterial Ulcers
2.3.3 Diabetic Foot Ulcers
2.3.4 Pressure Ulcers
2.3.5 Atypical Ulcers
2.4 Diagnosis
2.5 Multidisciplinary Approach
2.6 Conclusions
3: Anatomical Base for Diagnosis
3.1 Introduction
3.2 Classification of Leg Ulcers
3.2.1 Venous Ulcers Venous Anatomy of the Legs Physical Examination
Atrophie Blanche
Stasis Dermatitis
Pigmented Purpuric Dermatosis
3.2.2 Arterial Leg Ulcers
3.2.3 Diabetic Ulcers
3.2.4 Uncommon Type of Ulcers Hematological Ulcers Martorell’s Ulcer Lymphatic Ulcers
3.3 Differential Diagnosis Based on Clinical Features
3.3.1 Localization
3.3.2 Size of Ulcers
3.3.3 Symptoms
4: Wound Hygiene: From Traditional to Microenvironment in Cleansing
5: Principles of Antiseptic Treatments
5.1 Definition of Antisepsis
5.2 History of Antisepsis
5.3 Definition of Antiseptic Agent
5.4 The Bioburden in Skin and Wounds
5.5 Characteristics of Antiseptics
5.6 Indication of Antiseptic Treatment
5.6.1 Antiseptics in Surgery
5.6.2 Antiseptics in Wound Healing
5.7 Characteristics of Commonly Used Antiseptics
5.7.1 Chlorhexidine
5.7.2 Povidone-Iodine
5.7.3 Polyhexamethylene Biguanide
5.7.4 Silver
5.7.5 Hydrogen Peroxide
5.7.6 Superoxidized Solutions
5.7.7 Honey
5.8 Conclusions
6: The TIMEH Protocol
Part II: Dressing and Bandages
7: Ulcer Debridement
7.1 Debridement Overview
7.2 Autolytic Debridement
7.3 Enzymatic Debridement
7.4 Biological Debridement
7.5 Mechanical Debridement
7.5.1 Wound Irrigation
7.5.2 Pulsed Lavage
7.6 Sharp Debridement
7.7 Surgical Debridement
7.7.1 Hydrosurgery
7.8 Other Types of Debridement
7.8.1 Ultrasound Debridement
7.8.2 Laser Debridement
7.9 Factors to Consider in Choosing the Debridement Method
8: Advanced Moist Wound Dressing: Classification by Function
8.1 Classification by Function “Status-Based”
8.1.1 Dressings that Promote Autolysis and Debridement
8.1.2 Dressings that Promote Granulation Tissue Homeostasis of Fluids Bio-Induction
8.1.3 Antimicrobial Dressings
8.1.4 Re-Epithelializing Eudermal Dressings
8.2 Symptom-Based Dressings
8.3 Conclusions
9: Dressing: Indications on Applications
9.1 Introduction
9.2 Types of Wound Dressings
9.2.1 Gauze
9.2.2 Impregnated Gauze
9.2.3 Film
9.2.4 Hydrogel
9.2.5 Hydrocolloid
9.2.6 Foam
9.2.7 Alginate
9.2.8 Hydrofiber
9.2.9 Silver
9.2.10 Iodine
9.2.11 Tissue-Engineered Biological Dressings Non-Living Skin Substitutes Living Skin Substitutes
9.2.12 Other Types of Dressings
9.3 Negative Pressure Wound Therapy (NPWT)
9.4 Conclusions
10: Dressing in Burns
10.1 Introduction
10.2 Full-Thickness Burns
10.2.1 Skin Substitutes
10.3 Partial-Thickness Burns
10.3.1 Superficial Burns
10.3.2 Superficial Partial-Thickness Burns
10.3.3 Blister Management
10.3.4 Hydrogel Dressings
10.3.5 Hydrofiber Dressings
10.3.6 Alginates
10.4 Deep Partial-Thickness Burns
10.5 Facial Burns
10.5.1 Burn Cleansing
10.6 Chemical Burns
11: Innovative Dressings
11.1 TLC-NOSF Technology-Based Dressings
11.2 Hydroactive Dressings, Gelling Fiber Dressings, and 3D FIT Technology Dressings
11.3 Dressings with Hydrofiber and More Than Silver Technology
11.3.1 PluroGel® Burn and Wound Dressing
11.3.2 PluroGel® Burn and Wound Dressing with PSSD
11.3.3 Issue-Targeting Dressings
11.3.4 Activated Carbon-Based Dressings
11.4 Copper Antimicrobial Dressings
11.4.1 Dialkylcarbamoyl Chloride (DACC) Technology
11.5 Primary Wound Dressing Spray
12: Compression Therapy in Ulcer Care
12.1 Introduction
12.1.1 Evidence-Based Compression Therapy
12.1.2 Elastic and Inelastic Materials
12.1.3 Which Compression Material for Ulcer Treatment?
12.1.4 Comparing Compression Materials
12.1.5 Compression Therapy and Venous Hemodynamics
12.1.6 Is Inelastic Compression Always Mandatory for Ulcer Treatment?
12.1.7 Ulcer Recurrence Prevention
12.2 Special Circumstances
12.2.1 Compression Therapy and Mixed Leg Ulcers
12.2.2 Compression Therapy in Vasculitic Ulcers
12.2.3 Elastic or Inelastic Bandages in Patients with Leg Ulcers and Restricted Mobility?
12.2.4 Contraindications to Compression Therapy
12.3 Conclusions
Part III: Instrumental Treatments in Wounds
13: Scientific Principles and Clinical Application of Negative Pressure Wound Therapy (NPWT)
13.1 The Mechanisms of Action
13.2 The Possible Clinical Indications
14: Latest Applications of Negative Pressure Wound Therapy
14.1 Latest Applications of Negative Pressure Wound Therapy (NPWT)
14.1.1 Diabetic Foot
14.1.2 Pressure Ulcer Reconstruction
14.1.3 Flaps Venous Congestion
14.1.4 NPWT Prophylactically on Closed Incisional Wounds
14.2 New Perspectives
14.2.1 Breast Peri-Prosthesis Infection and NPTW
14.2.2 Fat Grafting and NPTW
14.3 Conclusions
15: Electrical Stimulation in Wound Care
15.1 Direct Currents
15.1.1 Low-Intensity Direct Current (LIDC)
15.2 Alternating and Pulsed Currents
15.2.1 Low-Intensity Pulsed Direct Current (LIPDC)
15.2.2 High-Voltage Pulsed Current (HVPC)
15.2.3 Simulated Biphasic ES (SSES)
15.2.4 Asymmetric Biphasic Electrical Stimulation
15.2.5 Symmetric Biphasic Electrical Stimulation (SBES)
15.3 Stochastic Currents
15.3.1 Decubitus Direct Current Treatment (DDTC)
15.3.2 Frequency Rhythmic Electrical Modulation System (FREMS)
16: Phototherapy in Wound Care
17: Laser in Wound Care
17.1 Laser in Wound Care
17.2 Debridement Laser
17.3 Biostimulation Lasers
18: Treatment of Chronic Wounds and Ulcers with Focused and Defocused Shock Waves
18.1 Introduction
18.2 Shock Waves
18.3 Aspects of Technology
18.4 The Biological Stimulus of the Shock Wave
19: Hydrosurgery in Wound Care
20: Ultrasound in Wound Care
20.1 Introduction
20.2 Device Characteristics
20.3 Mechanism of Action
20.4 Therapeutical Effects of Ultrasound on Chronic Wounds
20.5 Ultrasound Application in Relation to Different Wound Healing Phases
20.5.1 Inflammatory Phase
20.5.2 Proliferative Phase
20.5.3 Maturation or Remodeling
20.6 Treatment Protocols
21: Topical Oxygen in Wound Care
21.1 Introduction
21.2 Topical Oxygen Therapy: Clinical Trials
21.3 Topical Oxygen Therapy and Debridement
21.4 Topical Oxygen Therapy and Cost-Effectiveness
21.5 Retrospective Study
21.6 Cases (Courtesy of the Wound Care Unit, Kuala Lumpur Hospital)
21.7 Conclusion
Part IV: Regenerative Medicine and Tissue Bioingeneering
22: Evidence-Based and Clinical Experimentation on Cell Therapy
22.1 Background
22.2 Cells Suitable for Cell Therapy
22.2.1 Pluripotent Stem Cells
22.2.2 Embryonic and Extraembryonic Stem Cells
22.2.3 Adult Stem Cells
22.3 Evidence on Applicability of Cell Therapy in Ulcer Management
23: Bioinductive Dressing
23.1 Introduction
23.2 Bioactive
23.2.1 Bioactive Dressings
23.2.2 Drug-releasing dressings
23.3 Drug-Loaded Wound Dressing
23.3.1 Collagen
23.3.2 Biosynthesis and Degradation
23.3.3 Collagen & Tissue Repair Anti-Inflammatory Action Neoangiogenic Action Role in ECM Remodeling Dressings Hyaluronic Acid Honey
23.4 Honey and its Properties
23.4.1 Antibacterial Activity
23.4.2 Anti-Inflammatory Activity
23.4.3 Antioxidant Activity
23.4.4 Promoter of Wound Debridement
23.4.5 Neoangiogenesis Promoter
23.4.6 Promoter of Immune System Response Healing Promoter Limits to Use and Side Effects The Dressings
23.4.7 Effects on Different Types of Wounds Chronic Ulcers Burns Surgical Wounds Ozonids Mesoglycan DNA and Ribosomes Rigenase® Dressings MMPs Inhibitors
24: Skin Substitutes
24.1 Introduction
24.2 Characteristics and Composition
24.3 Classifications
24.4 Main Skin Substitutes on the Market
24.5 Clinical Overview
25: Mesenchymal Cells from Adipose Tissue
25.1 Introduction
25.2 Immunophenotype
25.3 Secretion of Growth Factors
25.4 Immunomodulatory Properties
25.5 Differentiation of ADSCs
25.6 Mesodermal Lines
25.6.1 Adipogenic Differentiation
25.6.2 Chondrogenic Differentiation
25.6.3 Osteogenic Differentiation
25.6.4 Myogenic Differentiation
25.7 Non-mesodermal Lines
25.7.1 Neuronal Differentiation
25.7.2 Hepatocyte Differentiation
25.7.3 Pancreatic Differentiation
25.7.4 Endothelial Differentiation
25.7.5 Epithelial Differentiation
25.7.6 Hematopoietic Differentiation
26: Peripheral Blood Mononuclear Cells
26.1 Background
26.2 Introduction
26.2.1 Autologous Peripheral Blood Mononuclear Cell-Based Therapy
26.2.2 New Therapeutic Strategies May Induce Immune-Modulation M1-M2
26.2.3 Role of the PBMNCs in Inducing New Vessel Formation
26.2.4 PBMNC Wound Healing in Critical Limb Ischemia and Diabetic Foot
26.2.5 PBMNCs in Autoimmune Disease
26.2.6 PBMNC-Based Therapy and Pain
26.2.7 Methods to Obtain Autologous PBMNCs
26.3 Tip and Tricks
26.4 Discussion
26.4.1 MSCs
26.4.2 Exosomes
26.4.3 Biomaterials
27: Platelet-Rich Plasma (PRP)
27.1 Introduction
27.1.1 Platelet-Rich Plasma
27.2 PRP Applications in Chronic Wounds
27.3 Operative Technique
27.3.1 PRP Injection
27.3.2 PRP Dressing
27.4 Clinical Applications of PRP in Diabetic, Venous, and Pressure Ulcers
27.4.1 Diabetic Ulcer
27.4.2 Lower Extremity Venous Ulcers
27.4.3 Pressure Ulcers
27.5 PRP Combination
27.6 Conclusions
28: Minimal Invasive Modality (MIMo) in Burn Wound Care
28.1 Introduction
28.2 Burns Standard of Care (SOC)
28.3 The Minimal Invasive Modality Treatment (MIMo) for Burn Care
28.3.1 Enzymatic Selective Escharolysis
28.3.2 Stem Cell Use in Burns
28.3.3 MIMo Operative Technique
28.3.4 Anesthetic Protocols and Settings of Treatment
28.3.5 Advantages of MIMo Compared to the SOC
28.4 Conclusions
29: Thermal Burns
29.1 Introduction
29.2 Local, Histomorphological Changes in a Burn Wound
29.2.1 General Changes
29.3 Admission of a Burn Patient
29.4 Burn Assessment
29.5 Surgical Treatment of Burns
29.6 Postoperative Care
29.7 Conclusion
Part V: Measurement and Documentation
30: Imaging and Measurement
30.1 Introduction
30.2 Overview of Imaging Technology in Wound Care
30.2.1 Optical Imaging in Wound Care
30.2.2 Overview of Nonoptical Imaging Techniques in Wound Care
30.3 Wound Measurement Techniques
30.3.1 Analog and Digital Measurement Methods
30.3.2 Neuromorphic Solutions in Wound Care
30.3.3 Clinical and Economical Advantages Resulting from the Use of Neuromorphic EDIs
30.4 Conclusions
31: Wound Measurement
31.1 Introduction
31.2 Clinical Wound Assessment
31.3 Wound Size Analysis
31.4 Wound Surface Area Measurement
31.4.1 Two-Dimensional Contact Methods Simple Ruler Method
31.4.2 Planimetric Measurement
31.4.3 Stereophotogrammetry
31.4.4 Digital Imaging
31.4.5 Wound Volume Measurement
31.4.6 Advanced Wound Imaging Methods Hyperspectral Imaging (HSI) Laser Doppler Imaging (LDI) Laser Speckle Imaging (LSI) Near-Infrared Spectroscopy (NIRS) Thermography
31.4.7 Other Devices Are as Follows Fluorescence Imaging (FLIM) Confocal Microscopy (CM) Ultrasound
31.5 Conclusion
32: Telemedicine and Artificial Intelligence
32.1 The Provider Center and the Service Center
32.2 Do Televisit Platforms Have to Be Medical Devices?
32.3 Electronic Prescription in Practice
32.3.1 Televisit
32.4 Return to Normality in Specialist Outpatient Clinics in the NHS
32.5 Artificial Intelligence
Part VI: Infection in Wound Care
33: Infection Diagnosis
33.1 Flora on the Skin: The Microbiome
33.1.1 Bacteria
33.1.2 Fungi
33.1.3 Viruses
33.2 Bacteria in Acute and Chronic Wounds
33.2.1 Acute Wounds
33.2.2 Chronic Wounds: Bacteria and Characteristics
33.3 Molecular Aspects: Interactions Between Bacteria and Their Influence on Wound Healing
33.4 Biofilm: Definition, Diagnosis, and Implications on Therapy
33.5 Wound Infection
33.6 How to Diagnose Wound Infection
34: Classification of Wound Infections
34.1 Introduction
34.2 Classification According to the Type of Wound (the Wound Healing Society System)
34.2.1 Acute Wounds: Burns, Traumatic Ulcers, and Bite Wounds
34.2.2 Diabetic Foot Ulcers
34.2.3 Venous Ulcers
34.2.4 Arterial Insufficiency Ulcers
34.2.5 Pressure Ulcers
34.3 Classification Systems
34.3.1 Available Skin and Soft Tissue Infection Classification Systems
34.3.2 Clinically Useful Classifications for Infected Wounds
34.4 Conclusions
35: Infected Wound Bed Management: The Diabetic Foot
35.1 Clinical Approach to the Diabetic Foot
35.1.1 The Multidisciplinary Diabetic Foot Team
35.2 Diabetic Foot Pathogenetic Factors
35.3 Neuropathic Foot
35.4 Ischemic Foot
35.4.1 Patient Risk Estimation
35.4.2 Limb Staging
35.4.3 Anatomic Pattern of Disease
35.5 Neuro-Ischemic Foot
35.6 Infected Foot
35.7 Diabetic Foot Life- or Limb- Threatening Infections
35.7.1 Deep Suppurative Infections
35.7.2 Necrotizing Fasciitis
35.7.3 Wet Gangrene
35.7.4 Erysipelas and Cellulitis
35.7.5 Osteomyelitis
35.8 Microbiology of Diabetic Foot Infections
36: Osteomyelitis
36.1 Introduction
36.2 Classification
36.3 Pathogenesis
36.4 Anatomo-Pathological Lesions
36.5 Pathogens
36.6 Diagnosis
36.6.1 Microbiology and Histopathology
36.6.2 Laboratory Studies
36.6.3 Imaging Procedures
36.7 Treatment
36.7.1 Acute Osteomyelitis
36.7.2 Chronic Osteomyelitis
36.7.3 Foot Infections
36.8 Conclusions
Part VII: Plastic Surgery: When and How
37: Grafting and Micrografting in Wound Care
37.1 Introduction
37.2 Skin Grafts
37.2.1 History
37.2.2 Classification
37.2.3 Meshing Techniques
37.2.4 Preparation of the Wound Bed
37.2.5 Indications for the Use of Skin Grafts
37.2.6 Contraindications
37.2.7 Epidermal Grafts
37.2.8 Wound Healing and Fat Graft
37.3 History and Development of Micrografting Technique
37.3.1 The Pinch Graft
37.3.2 Patch/Postage Stamp Graft
37.3.3 The Intermingled Technique
37.3.4 Microskin Graft
37.3.5 Microscopic Split-Skin “Diced” Graft
37.3.6 Fine-Particle Graft (Autologous Skin Suspension)
37.3.7 Micrograft Spray
37.4 The Meek Technique
37.4.1 The Modified Meek Graft Procedure
37.5 Fields of Application of Micrografts
37.5.1 Burns
37.5.2 Chronic Wounds
37.5.3 Treatment of Scars
38: Surgical Debridement in Wound Care
38.1 Introduction
38.2 Definition
38.3 Surgical or Sharp Debridement
38.3.1 Surgical Debridement
38.3.2 Sharp Debridement
38.4 Instruments
38.5 Aim of the Debridement
38.6 Wounds to Debride
38.6.1 Contraindications
38.6.2 Debridement in Diabetic Foot [22] Neuropathic Ulcer Neuroischemic Ulcer Infected Neuropathic Ulcer Infected Ischemic Ulcer Additional Surgery
38.7 Larvatherapy
39: Reconstructive Options in Wound Care: From Simplest to Most Complex
39.1 Introduction
39.2 Management of Chronic and Pressure Ulcers
39.3 Conservative Treatment and Wound Care
39.4 Surgical Indications
39.5 Surgical Debridement
39.6 Reconstruction Methods
39.6.1 Primary Closure
39.6.2 Skin Grafting
39.6.3 Flaps
39.7 Reconstructive Procedures by Site
39.7.1 Sacral Ulcers
39.7.2 Ischial Ulcers
39.7.3 Trochanteric Ulcers
39.7.4 Heel Ulcers
39.7.5 Elbow Olecranon Ulcers
39.7.6 Posterior Scalp (Occiput) Ulcers
39.7.7 Atypical Locations of Pressure Ulcers during COVID-19 Pandemic
39.8 Conclusions
40: Surgical Indications in All Diagnostic and Care Pathways (DTCP) Settings
40.1 Introduction
40.2 Etiological Classification and General Assessment
40.3 Common Principles of Treatments
40.3.1 Debridement
40.3.2 Infection Control
40.3.3 Wound Bed Preparation (WBP)
40.3.4 Wound Closure
40.4 Indications for Hospital Surgical Referral in the DTCP
40.5 Specific Recommendations Based on Ulcer Subtype
40.5.1 Venous Ulcers Operative Management
40.5.2 Pressure Ulcers Operative Management
40.5.3 Arterial Ulcers Operative Management
40.5.4 Diabetic Foot Ulcers Operative Management
40.5.5 Neoplastic Ulcers Operative Management
40.5.6 Vasculitic Ulcers Operative Management
40.5.7 Infected Ulcers Operative Management
40.6 Conclusion
41: Microsurgery in Wound Healing
41.1 Introduction
41.2 Patient Selection, Multidisciplinary Approach, and the Wound Preparation
41.3 Surgical Techniques
41.3.1 Case Examples Case 1 Case 2 Case 3
41.4 Outcomes
41.5 Conclusion
42: Advanced Reconstruction in Wound Care
42.1 Background
42.2 Advanced Reconstruction in Wound Care
42.3 Discussion on Other Issues
42.3.1 Venous Ulcers
42.3.2 Diabetic Ulcers
42.3.3 Pressure Sores
42.4 Conclusion
43: Lower Limb Ulcers: Clinical and Diagnostic Workout
43.1 Introduction and General Framework
43.1.1 Introduction
43.1.2 Medical History and Clinical Examination
43.1.3 Clinical Diagnostic Criteria
43.1.4 Instrumental Diagnostic Criteria
43.1.5 Laboratory Diagnostic Criteria
43.2 Differential Diagnosis
43.2.1 Vascular Ulcers Venous-Based Ulcers Arterial-Based Ulcers Mixed Vascular-Based Ulcers Vasculitic-Based Ulcers
43.2.2 Diabetic Ulcers
43.2.3 Post-traumatic Ulcers
43.2.4 Pressure Ulcers
43.2.5 Edema Ulcers
43.2.6 Infectious-Based Ulcers Tropical Ulcers Infective Ulcers of Other Nature Osteomyelitis Ulcers
43.2.7 Neoplastic Ulcers [15] Squamous Cell Carcinoma Ulcer Basal Cell Carcinoma Ulcer Ulcerated Melanoma Sarcoma Ulceration Ulcerated Lymphoma
43.2.8 Other Ulcers [16] Steroid Ulcers Neuropathic Ulcers Dermatitis Ulcers
Part VIII: Ulcer Management Further Issues
44: Wound Care in Aesthetic Surgery
44.1 Wound Healing: An Aesthetic Perspective
44.1.1 Scar Outcome
44.1.2 Dressings in Aesthetic Surgery Blepharoplasty Mammoplasty Rhytidectomy Lipoaspiration Abdominoplasty
44.2 Wound Management
44.3 Complications Management
44.3.1 Wound Dehiscence and Necrosis
44.3.2 Seroma in Abdominoplasty
44.3.3 Altered Scar Formation
44.4 Conclusion
45: Correction of Postural Deficit Promoting Lower Limb Hemodynamics, for Feet Proprioceptive Stimulation
45.1 Introduction
45.1.1 Skin Lesions and Pathologies of the Micro and Macro-circulation of the Lower Limbs
45.1.2 Biomechanical Anomalies of the Foot
45.1.3 The Diagnosis and the Postural Assessment
45.2 Materials and Methods
45.2.1 In General
45.2.2 The Upright Unperturbed Stance
45.2.3 The Balance Force Plate
45.2.4 Postural Exam
45.2.5 Podoscope and Baropodoscope
45.2.6 The Rehabilitation Program
45.3 Aspects of Foot Neurophysiology: The Podiatric Receptors
45.4 Hemodynamic Aspects
45.4.1 Muscles and Blood Flow
45.4.2 Plantar Pump: The Lejar’s Slab
45.4.3 Calf Muscles Pump
45.5 Baroproprioceptive Insoles (Gobyte)
45.5.1 The Proprioceptive Stimulation Insole
45.6 An Application Example
45.6.1 The Patient
45.6.2 Plantar Support Assessment with Foot Analyzer
45.6.3 Insoles Customization
45.7 Discussion and Conclusion
46: Pain Management
46.1 Introduction
46.2 Pathophysiology of Pain
46.3 Nociception
46.4 Pain Modulation Neurotransmitters
46.5 The Perception of Pain
46.6 Description of the Pain
46.7 Neuropathic Pain
46.8 Assessment of Pain in Adulthood in the Patient with Skin Lesions
46.8.1 Verbal Rating Scale—VRS [64, 65]
46.8.2 Numerical Rating Scale—NRS [66]
46.8.3 Visual Analogical Scale—VAS [67]
46.8.4 Pain Assessment in an Evolving Society
46.9 How Culture Affects Pain: Stoicism vs. Expressiveness
46.10 Procedural Pain
46.11 Pain Management in Skin Lesions
46.12 Pain Management Related to Medication
46.13 A (Old) New Frontier, Topical Anesthetics
47: Nutrition and Metabolism
47.1 Obesity and Adiposopathy
47.2 Obesity in Wound Healing
47.3 Nutrition in Wound Healing
48: Diabetic Foot Management
48.1 Introduction
48.2 The Pathogenesis of DFS
48.3 Assessment of Patients with DFS
48.3.1 History and Physical Examination
48.3.2 Diagnosis of PN
48.3.3 Diagnosis of PAD
48.3.4 Diagnosis of Infection
48.3.5 Diagnosis of CN
48.4 Management of Patients with DFS
48.4.1 Offloading Management of CN
48.4.2 Management of PAD
48.4.3 Management of Infection
48.4.4 Management of the Wound bed
48.4.5 Management of Glycemic Control
48.5 Follow-Up
49: Ozone Therapy in Wound Care
49.1 Introduction
49.1.1 Ozone Therapy and Mechanism of Action
49.1.2 Ozone Therapy in Orthopedy
49.1.3 Ozone Effect in Odonthoiatry
49.1.4 Ozone Effects on Infections
49.1.5 Potential Mechanisms of Ozone Therapy in Infections Antimicrobial Effect
49.1.6 Antioxidant Defenses
49.1.7 Immunoregulatory Effects
49.1.8 Epigenetic Modulation
49.2 Conclusions
50: Malignant Wound Care and Advanced Illness Management
50.1 Introduction
50.2 Cancerous Wound Assessing Tools
50.3 Radiology, Radiotherapy and Systemic Chemotherapy
50.4 Interventional Perspectives: Ablative and Reconstructive Palliative Surgery
50.5 Dressings and Topical Agents
50.6 Pain Management and Psychosocial Support
51: The Prevention of Ulcer Recurrence
51.1 Venous Leg Ulcers
51.2 Pressure Ulcers
51.3 Diabetic Foot Ulcers
51.4 Arterial Leg Ulcers
51.5 Conclusions
52: Rehabilitation in Wound Care in Adult Population
52.1 A Teamwork Care
52.2 Physiotherapy in Wound Care
52.2.1 Areas of Concern
52.2.2 Assessment Process
52.3 Principles of Physiotherapy Treatment in Wound Care
52.4 Biophysical Agents
52.5 Types of Wounds and Physiotherapy Treatment
52.5.1 Physiotherapy Management of Patients with Pressure Injuries Repositioning and Early Mobilization
52.5.2 Physiotherapy Management of Patients with Diabetic Foot Ulceration Prevention of Diabetic Foot Wounds Effects of Exercise on Diabetic Wound Healing
52.5.3 Physiotherapy Management of Patients with Vascular Insufficiency Venous Ulcers Arterial Ulcers
52.5.4 Physiotherapy Management of Patients with Acute and Chronic Edema Types of Lymphedemas Implications of Lymphedema: Chronic Wounds
52.6 Final Comments
53: Lymphedema and Wound Care
53.1 Lymphedema Overview
53.2 Clinical Diagnosis of Lymphedema
53.3 Imaging Diagnosis of Lymphedema
53.4 Principles of Lymphedema Treatment
53.4.1 Non-surgical Treatment
53.4.2 Surgical Treatment
53.4.3 Lymphedema Skin Care
53.4.4 Lymphedema Wound Care
54: Budget and Quality in Dressings
54.1 Introduction
54.2 Budget Setting for the Purchase of Advanced Dressings
54.3 Budgeting Procedure
54.4 The Quality Parameter for Tender Procedures for the Purchase of Advanced Medications
54.4.1 Alginate Dressings
54.4.2 Hydrocolloid Dressings
54.4.3 Hydrofiber Dressings
54.4.4 Hydrophilic Gel Dressings
54.4.5 Alginate and Silver Dressings
54.5 Dressings Consisting of Gauze and Substances with Emollient Action
55: Update on Technology and Evidence-Based Management of Scars
55.1 Introduction
55.2 Biological Resume of Events Occurring After a Skin Injury
55.3 Factors Impacting Scars
55.3.1 The Young Age
55.3.2 The Elderly
55.3.3 The Reappearance of a Wound on a Scar
55.3.4 Degenerescence/Marjolin’s Ulcer
55.3.5 Hyperkeratosis
55.4 Generic Principles of Scar Management Depending on the Time of Onset After Healing
55.5 Scar Assessment Scales
55.6 Non-surgical Technologies
55.7 Non-surgical Technologies
55.7.1 Intra-lesional Steroid Injections
55.7.2 Silicone Gel/Sheet
55.7.3 Radiotherapy
55.7.4 Photodynamic Therapy (PDT)
55.7.5 Electrical Stimulation
55.8 Surgical Strategies
55.9 Z Plasties
55.10 Skin Grafts
55.11 Dermal Substitutes
55.12 Flaps
55.13 Scar Prevention
55.13.1 Lasers
55.13.2 Postoperative Mechanotherapy Adhesive Sutures The Zip® System Incisional Negative Pressure Wound Therapy
55.14 Conclusion

Citation preview

Pearls and Pitfalls in Skin Ulcer Management Michele Maruccia Giovanni Papa Elia Ricci Giuseppe Giudice Editors


Pearls and Pitfalls in Skin Ulcer Management

Michele Maruccia Giovanni Papa  •  Elia Ricci Giuseppe Giudice Editors

Pearls and Pitfalls in Skin Ulcer Management

Editors Michele Maruccia Unit of Plastic and Reconstructive Surgery, Department of Precision and Regenerative Medicine and Jonic Area University of Bari Bari, Italy Elia Ricci Difficult Wound Healing Unit Policlinico di Monza Vercelli, Italy, Italia

Giovanni Papa Plastic Surgery Unit University of Trieste, Cattinara Hospital Trieste, Italy Giuseppe Giudice Plastic and Reconstructive Surgery University of Bari Aldo Moro Bari, Italy

ISBN 978-3-031-45452-3    ISBN 978-3-031-45453-0 (eBook) The volume editors and authors gratefully thank professor Chiara Fedele from the University Aldo Moro (Bari, Italy) for the English language review of the book. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Paper in this product is recyclable


Wound care presents various challenges and complexities, requiring a multidisciplinary approach with input from specialists in different fields. While some wounds heal quickly with minimal intervention, others can become chronic and lead to complications such as infections, delayed healing, and amputations. To address the needs of healthcare professionals involved in ulcer management, a team of world experts in the field has compiled Pearls and Pitfalls in Skin Ulcer Management. This is a comprehensive guidebook, with the participation of experts from two major Italian recognized scientific societies (approved by the Ministry of Health) specializing in chronic ulcers, wound healing, and plastic, aesthetic, regenerative, and reconstructive treatments: AIUC (Italian Association for Cutaneous Ulcers) and SICPRE (Italian Society of Reconstructive, Regenerative Plastic Surgery). The book covers all aspects of wound care and is divided into eight main parts. Part I provides an introduction to wound care, including cleansing, antiseptics, and local treatment. The second part covers dressing and bandages, discussing the different types, their advantages and disadvantages, and indications for their use. Part III discusses instrumental treatments, including hydrosurgery, negative pressure wound therapy, and photobiomodulation. Regenerative medicine and tissue bioengineering, including the use of growth factors and stem cells, are covered in Part IV. Measurement and documentation, infection in wound care, the role of plastic surgery, and other aspects of ulcer management are discussed in Parts V through VIII. Each chapter includes practical tips, case studies, and real-world examples to help readers apply the information to their own practice. The book’s goal is to be a practical and accessible resource for healthcare professionals at all levels of experience. It is a valuable “survival manual” for the management of complex wounds and ulcers and may inspire collaboration among different specialties to improve patient outcomes.




The authors extend their sincere gratitude to the contributors who made this book possible, including the multidisciplinary team of experts and the publisher. They hope that healthcare professionals will find this book to be a valuable addition to their library and an indispensable resource in their clinical practice. Bari, Italy Trieste, Italy  Pecetto Torinese, Torino, Italy  Bari, Italy 

Michele Maruccia Giovanni Papa Elia Ricci Giuseppe Giudice


Part I Introduction to Wound Care, Cleasing, Antiseptic and Local Treatment 1 Vulnology  (Also Known as Wound Care): History and Myths of Chronic Wounds ������������������������������������������������������   3 Elia Ricci and Monica Pittarello 2 Aetiology,  Classification and Advocating for a Holistic, Multidisciplinary Approach������������������������������������������������������������  11 Alessandra Michelucci, Giammarco Granieri, Valentina Dini, and Marco Romanelli 3 Anatomical  Base for Diagnosis ������������������������������������������������������  21 Iris Zalaudek and Michele Pauluzzi 4 Wound  Hygiene: From Traditional to Microenvironment in Cleansing��������������������������������������������������������������������������������������  27 Arturo Caniglia 5 Principles of Antiseptic Treatments������������������������������������������������  33 Elisabetta Iacopi, Francesco Giangreco, and Alberto Piaggesi 6 The TIMEH Protocol����������������������������������������������������������������������  53 Claudio Ligresti Part II Dressing and Bandages 7 Ulcer Debridement��������������������������������������������������������������������������  63 Tedeschi Pasquale and Michele Maruccia 8 Advanced  Moist Wound Dressing: Classification by Function ��������������������������������������������������������������������������������������  75 Alessandro Greco, Mastronicola Diego, Natascia Mennini, and Magnoni Cristina 9 Dressing: Indications on Applications��������������������������������������������  89 Gianmarco Turriziani, Federico Lo Torto, and Diego Ribuffo 10 Dressing in Burns ���������������������������������������������������������������������������� 101 Antongiulio Mangia, Agostino Rodda, and Antonio Di Lonardo vii


11 Innovative Dressings������������������������������������������������������������������������ 113 Evelin Makuc 12 Compression  Therapy in Ulcer Care���������������������������������������������� 123 Giovanni Mosti Part III Instrumental Treatments in Wounds 13 Scientific  Principles and Clinical Application of Negative Pressure Wound Therapy (NPWT)���������������������������� 141 Franco Bassetto and Scarpa Carlotta 14 Latest  Applications of Negative Pressure Wound Therapy���������� 149 Laura Torrano, Susana López, and Gemma Pons 15 Electrical  Stimulation in Wound Care ������������������������������������������ 155 Elia Ricci 16 Phototherapy in Wound Care �������������������������������������������������������� 163 Fabrizio Malan 17 Laser in Wound Care���������������������������������������������������������������������� 167 Elia Ricci 18 Treatment  of Chronic Wounds and Ulcers with Focused and Defocused Shock Waves������������������������������������ 175 Raoul ul Saggini, Rosa Grazia Bellomo, and Andrea Saggini 19 Hydrosurgery in Wound Care�������������������������������������������������������� 181 Ferdinando Campitiello 20 Ultrasound in Wound Care ������������������������������������������������������������ 183 Alessandro Scalise, Ortensia Pirro, Cesare Foggetti, Marina Pierangeli, Matteo Torresetti, and Giovanni Maria Di Benedetto 21 Topical  Oxygen in Wound Care������������������������������������������������������ 195 Harikrishna K. R. Nair Part IV Regenerative Medicine and Tissue Bioingeneering 22 Evidence-Based  and Clinical Experimentation on Cell Therapy�������������������������������������������������������������������������������� 205 Andrea Ferrari, Chiara Stocco, Roberta Bulla, Serena Zacchigna, and Giovanni Papa 23 Bioinductive Dressing���������������������������������������������������������������������� 215 Francesco D’Andrea and Francesca Mosella 24 Skin Substitutes�������������������������������������������������������������������������������� 245 Vito Cazzato, Grace Marchi, Maria Giulia Spazzapan, and Giovanni Papa




25 Mesenchymal Cells from Adipose Tissue �������������������������������������� 263 Paolo Persichetti, Giovanni Francesco Marangi, Carlo Mirra, Marco Gratteri, and Lucrezia Arcari 26 Peripheral  Blood Mononuclear Cells �������������������������������������������� 273 Sara Carella and Maria Giuseppina Onesti 27 Platelet-Rich Plasma (PRP)������������������������������������������������������������ 289 Valerio Cervelli and Andrea A. Pierro 28 Minimal  Invasive Modality (MIMo) in Burn Wound Care���������� 299 Alessio De Cosmo, Giuseppe Di Gioia, Giulio Maggio, and Giuseppe Giudice 29 Thermal Burns �������������������������������������������������������������������������������� 307 Albin Stritar and Marko Mikša Part V Measurement and Documentation 30 Imaging and Measurement ������������������������������������������������������������ 317 Jacopo Secco 31 Wound Measurement���������������������������������������������������������������������� 339 Valentina Dini and Giammarco Granieri 32 Telemedicine and Artificial Intelligence���������������������������������������� 347 Michele Blasina, Martina Pangos, and Sergio Pillon Part VI Infection in Wound Care 33 Infection Diagnosis�������������������������������������������������������������������������� 357 Giovanni Papa, Paola Pini, Stefano Di Bella, and Giulia Benedetta Sidoti 34 Classification of Wound Infections ������������������������������������������������ 369 Matteo Bassetti, Antonio Vena, and Nadia Castaldo 35 Infected  Wound Bed Management: The Diabetic Foot���������������� 385 Giacomo Clerici, Fabrizio Losurdo, Andrea Casini, Iulia Valeria Rusu, and Robert G. Frykberg 36 Osteomyelitis������������������������������������������������������������������������������������ 405 Giovanni Vicenti, Guglielmo Ottaviani, and Biagio Moretti Part VII Plastic Surgery: When and How 37 Grafting  and Micrografting in Wound Care �������������������������������� 417 Alberto Bolletta, Davide Di Seclì, Mirco Pozzi, and Emanuele Cigna


38 Surgical  Debridement in Wound Care ������������������������������������������ 429 Stefano Bottosso, Silvia Pasquali, Riccardo Ricci, and Zoran M. Arnež 39 Reconstructive  Options in Wound Care: From Simplest to Most Complex���������������������������������������������������� 439 Marco Pappalardo, Francesca Lolli, Melba Lattanzi, and Giorgio De Santis 40 Surgical  Indications in All Diagnostic and Care Pathways (DTCP) Settings �������������������������������������������� 453 Emanuele Cammarata, Francesca Toia, Antonino Speciale, Martina Maltese, Tiziano Pergolizzi, and Adriana Cordova 41 Microsurgery in Wound Healing���������������������������������������������������� 467 Joon Pio Hong and Asli Datli 42 Advanced  Reconstruction in Wound Care������������������������������������ 481 Hung-Chi Chen and Burak Kaya 43 Lower  Limb Ulcers: Clinical and Diagnostic Workout���������������� 499 Vittorio Ramella, Martin Iurilli, Alessia De Grazia, and Laura Grezar Part VIII Ulcer Management Further Issues 44 Wound  Care in Aesthetic Surgery�������������������������������������������������� 511 Valeriano Vinci, Riccardo Di Giuli, Ana Paula Fontoura Andrade Reis, and Marco Klinger 45 Correction of Postural Deficit Promoting Lower Limb Hemodynamics, for Feet Proprioceptive Stimulation������������������ 523 Gianluca Bernabei 46 Pain Management���������������������������������������������������������������������������� 537 Angela Peghetti, Roberta Seri, Enrica Cavalli, and Valentina Martin 47 Nutrition and Metabolism�������������������������������������������������������������� 571 Lucilla Crudele, Marica Cariello, and Antonio Moschetta 48 Diabetic Foot Management ������������������������������������������������������������ 581 Irene Caruso, Anna Leonardini, Francesca Guarini, Mattia Bernardis, Luca Cellamare, Ilaria Immacolata Matichecchia, Rebecca Annicchiarico, Aurelia Bellomo Damato, Luigi Laviola, and Francesco Giorgino 49 Ozone Therapy in Wound Care������������������������������������������������������ 593 Fabio Sallustio, Marco Fiorentino, Paola Pontrelli, Mariagiovanna Di Chiano, Annalisa Casanova, Nicla Campobasso, and Loreto Gesualdo




50 Malignant  Wound Care and Advanced Illness Management������ 611 Marco Marcasciano, Jacopo Nanni, Antonello Greto Ciriaco, Maria Antonia Fiorillo, Donato Casella, and Manfredi Greco 51 The  Prevention of Ulcer Recurrence���������������������������������������������� 623 Vincenzo Lauletta 52 Rehabilitation  in Wound Care in Adult Population���������������������� 633 Susanna Mezzarobba and Lucia Chierici 53 Lymphedema and Wound Care������������������������������������������������������ 649 Rossella Elia and Michele Maruccia 54 Budget  and Quality in Dressings���������������������������������������������������� 661 Francesco Petrella and Giovanni Papa 55 Update  on Technology and Evidence-Based Management of Scars���������������������������������������������������������������������� 673 Luc Téot, Hester Colboc, and Sylvie Meaume

Part I Introduction to Wound Care, Cleasing, Antiseptic and Local Treatment


Vulnology (Also Known as Wound Care): History and Myths of Chronic Wounds Elia Ricci and Monica Pittarello

The name “vulnology” was conceived in memory of Arcagatus, a protophysician of Greek origin who worked in Rome [1]. Born in the third century BC in Sparta in the Peloponnese, son of Lisania, he migrated to Rome in 219 BC. As an important figure, he is described by Pliny, in the seventies of the first century. Pliny, the elder, speaks in a polemical tone about the penetration of Hellenic medicine in Rome, attributing it to the Hippocratic physician Arcagatus of Lisania, who arrived in the city under the consulate of Lucius Aemilius Paulus and Marcus Livius Salinator (219  BC). Arcagatus would have obtained Roman citizenship and the possibility of exercising in an iatreion (“medical workshop”), purchased with public funds in the Acilio task, in what will remain the area of medical practice in Rome until the time of Galen, in the second century [2]. He himself reports that Arcagato was a master in treating wounds, and for this reason, he was called Vulnerarius, but making too casual use of surgical instruments, especially the scalpel and cautery, and an excessive recourse to amputations; he was nicknamed Carnifex, “the executioner.”

E. Ricci (*) · M. Pittarello Difficult Wound Healing Unit, Policlinico di Monza, Vercelli, Italia, Italy

Ancient Roman medicine, based on body hygiene and magic, tolerated little Hellenic or Hippocratic medicine. Another thing of which the hellenic doctors were accused was to demand payment for this type of service, this would justify the purchase of the medical taberna with public funds. Cato the censor, his contemporary, railed against Hellenic medicine and spoke of exile. But studies conducted by Buck [3]. then taken up by Bonadeo [4] cast doubt on this hypothesis. With in conjunction with his disappearance from the scene the birth of an important Roman family, the Gens Acilia precisely. The importance of Arcagato is undoubted as demonstrated by an intact Greek papyrus [5] where a certain Chairas writes to the doctor Dionisyos to obtain clarification on ointments, the letter of which the translation is reported in Fig. 1.1, dated April 26, 59 AD, shows how over 250 years later the “plaster of Arcagato” was still in use. Of the ointment or patch of Arcagato we came to the recipe, composed of minium (lead oxide 1 and 4), burnt copper, cerussa (white dye), turpentine (oily vegetable resin) and litharge (lead oxide) obviously all these components had an antibacterial function [6]. The name vulnology [7, 8] is derived from the terms vulnus (wound) and logos (study but also word) in honor of Arcagatus the Vulnerarius. The term was born to give dignity and a name to an art as old as the human race. The name is currently evolving in the Anglo-Saxon culture where we

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



E. Ricci and M. Pittarello

Charias greets his dearest Dionysios very much and wishes him health forever. When I received your letter I was so extraordinarily happy, as if I had really been with you, in fact except this (letter), there is nothing else. I omit writing great thanks to you: in fact it is necessary to thank with words those who are not friends. I am persuaded to force myself with a certain tranquility, and if not the equivalent, I will give you at least a part of the affection you feel for me. You sent me two versions of recipes, one for Arcagato ointment, the other for healing ointment. The one from Arcagato is composed correctly, while the one from the healing agent lacks the resin dosage. Please let me know about an energetic healing agent that is able to heal the soles of the feet without risk, since I need it urgently. As for the hard one, you wrote to me that there are 2 types; send me the written recipe for the dispersant; in fact even the tetradrug is of the hard type. This letter is sealed. I salute you and remember what I said. (year) 5th of Nero the Lord, (day) 1st (of the month of) Germanicus. A. Dionysius Medicus

Fig. 1.1  Translation of the papyrus P. Merton I

Fig. 1.2  Fresco from Herculaneum with Achilles and the centaur Chiron, preserved at the Archeological Museum Naples, Italy (Inventory MANN). Figure under public domain, Photo credits: Giorgio Albano

begin to talk about woundology [9]. We could talk about vulnology in all fields of human history, from mythology, to religion, to art in general, in history, but it would be a separate book, and we will give here a few hints in the various sectors. The history of vulnology begins in ancient times, and it has roots in mythology and history. The father of medicine in Hellenic culture was the centaur Chiron (Fig. 1.2), son of the titan Cronus, and the oceanine Filiria who had a relationship in the form of horses, the curse of Hera on the illegitimate son, gave rise to the centaur [10]. Abandoned, he was adopted by Apollo and Athena, and he grew up in a cave in Thessaly

[11]. He was master to many demigods and heroes such as Achilles, Heracles (or Hercules), Asclepius, Actaeon, Peleus, Jason, Palamedes, Aeneas, Aristeus and Actaeon, Cephalus, Dioscuri, Nestor, Macaon, Castor and Pollux, Theseus, Amphiaraus, Meleager, Telamon, Hippolytus, Icifle, and Ulysses. Chiron in fact was famous for the treatment of wounds in general, what we now call ulcers were then called “Chironian” in his honor. From him originates the name of the gentian who was then called Chironia, precisely because it was used by the centaur in wound care, a plant already known for its anti-inflammatory properties. Then, Chiron is famous for its culture, which he transmitted to humans. The death of Chiron is interesting: Ovid in the Glories tells that “… while the old man was handling the horrible arrows, for the poison, one fell and struck his left foot. Chiron shouted and pulled the iron out of his limb; Alcide and the child Emonius (Achilles) groaned. The centaur, meanwhile, stirred (in a container) herbs picked on the Pegasei mountains; then with those medicines he tried to soothe the wound; but the poison was stronger than the medicament, and the evil spread deep into the bones and throughout the body; the blood of the hydra Learnea, mixed with that of the centaur, left no time for any help.” According to Antisthenes, the wound would be due to an accidental shot of Heracles that hit him in the knee, but as a demigod he was immortal, and he could not die and the pain became unbearable, so he asked Zeus for the gift of death, not being able to leave the position vacant, Prometheus, his pupil, offered himself as a vol-

1  Vulnology (Also Known as Wound Care): History and Myths of Chronic Wounds

unteer, and Chiron was transformed into the constellation of Sagittarius to eternal memory. The story of Chiron in vulnology continues with his students; first of all, the titan Prometheus, his heir who, for having brought fire to men, which today symbolizes knowledge, would be punished by the gods with an eternal torture, chained to a rock by Vulcan, to be torn apart by Aithon during the day, a monstrous eagle, which would eat his liver, being him immortal, during the night the liver would grow back and the cycle would start again the following day. Prometheus will be freed by Heracles, putting an end to his torture freeing him. What a wonderful evolution, from the father of vulnology, the myth of tissue regeneration and chronicity cured with gentian, the control of inflammation. Of his students, the most famous in medicine will be Asclepius who, for his ability as a doctor, will be disliked by Hades as he is capable of recalling the dead. Put to death by Zeus, who will later repent his choice and turn him into the god of medicine. According to Pindar [12], Asclepius had no surgical skills, and he only treated wounds and ulcers of external origin, in most cases, wounds from spears and arrows, and only on these, he used to apply his remedies; for others, he frequently resorted to spells, magic formulas, hymns, and invocations to the gods. The inventor of the Panacea had, according to some, five daughters; according to others, his descendant would be Macaone, who had an important part in Troy. Many of the Argonauts were students of Chiron, the journey in the white ship, whose meaning reminds us of the Grail and as such a search with a final test. The Golden Fleece had the ability to heal wounds if wrapped in it. The Golden Fleece was, according to Greek mythology, the golden mantle of Chrysomar, a winged ram capable of flight, which Hermes gave to Nepheles, mother of Jason. The Argonauts will make the journey and obtain the fleece thanks to Medea. The trial, having Jason betrayed his lover Medea, would not be passed, and the hero would be punished. In the myth, there is also the story of Philoctetes, who was the bearer of Heracles’ weapons and had sworn never to reveal the location of the tomb but


betrayed the oath and was punished. Most of the original works are lost, and we have two versions of the punishment [13]. In one, the wound occurs through one of the Heracles’ arrows (soaked in the hydra poison Learnea ed), and in the second, the wound occurs bitten by the viper in custody of the tomb. It resulted in a wound so foul-­ smelling that for 10 years he was confined to the island of Lemnos. Resumed for the Trojan War, it would be cured by Macaone, a pupil or son of Aesculapius with Pramna wine, honey, onion, and flour. It will be Philoctetes who, by killing Paris, will determine the beginning of the fall of Troy. Still here a wound as punishment of the divine. In religion, vulnology is very well represented, just think that in the Bible it is the most cited pathology, found in 129 verses [14]. Here, we find the concept of plague as divine punishment well rooted (Psa. 38: 5 My wounds are fetid and purulent for my folly), standards of care (Isaiah 38:21 Isaiah had said, “Take a poultice of dried figs, apply it to the ulcer, and the king will heal.”), hygiene rules (Leviticus 13: 27 On the seventh day, the priest will examine it, and if the stain has spread on the skin, the priest will declare it impure: It is a plague of leprosy), and finally as proof of faith, think of job. The martyrs attained holiness through the wounds that Christian iconography depicts precisely as blissful images. Perhaps the most famous wounds are those of the crucified Christ, and through this the representation of the Stigmata, the first of which is attributed to St. Francis of Assisi, and to date about 800 saints have been made. St. Camillus, suffering in the past from an ulcer, after conversion, will devote himself to assisting the sick, especially the wounded, and is the protector of nurses. We include Saint Isabella of Portugal for the care of ulcer bearers and Saint Roch as a bearer of ulcers as atonement. Finally, the Miracle of Saints Cosmas and Damian performed the first transplant in history by replacing a gangrenous limb. Wounds and cures have been depicted in art since ancient times, from the wounded man represented in the caves of Lascaux in the Upper


E. Ricci and M. Pittarello

Fig. 1.4  Wounded Philoctetes at Lemnos, Attic Vase circa 420  B.C. (Collection of the Metropolitan Museum New York, figure under public domain) Fig. 1.3  Mural in Pompeii, Lapige cleanses the wounds of Aeneas 45–79  A.D.  Archeological Museum Naples, Italy (Inventory MANN). Figure under public domain

Paleolithic, to the famous fresco of Pompeii where Lapige cleanses the wounds of Aeneas (Fig. 1.3), or the representations of Philoctetes on the Attic vases of Magna Graecia (Fig. 1.4). Over the centuries, art depicted religious subjects or the powerful and then religious ones prevailed, of which the main representation was that of the Martyrs. In these depictions, the wound often emits light, or the expression of the martyrs suggests a relationship with the divine, as depicted in Fig. 1.5. This is also true in sculpture where, in my opinion, above all is the sculpture of Santa Cecilia by Stefano Maderno, in which the girl appears as sleeping and the horrendous wound by beheading looks almost like a jewel (Fig.  1.6), beautiful the combination with the painting of Riminaldi (1620) of Palazzo Pitti where an angel oversees everything on martyrdom. In the twenty-­ seventh century, with the new pictorial currents Fig. 1.5  Saint Lucia: Carlo Dolci 1687, Palatine Gallery, we begin to represent everyday life, and here also the Uffizi, Florence, Italy (figure under public domain)

1  Vulnology (Also Known as Wound Care): History and Myths of Chronic Wounds


Fig. 1.6 Saint Cecilia Martyr, sculpted by Stefano Maderno, 1600, preserved in the Basilica of Santa Cecilia, Trastevere, Rome, Italy (figure under public domain)

appear the wounds, from Teniers who in the seventeenth century depicts a dressing in a house, to Ryckaert who in 1638 depicts the surgeon until that day, thousands perhaps millions of paintings represent wounds and ulcers, and I would like to conclude, however, with the work “The broken column” by Frida Khalo (Fig. 1.7), the result of a personal experience that however expresses well what is the life of the carriers of skin ulcers. We could write books, but I would like to move on to the last part, history. On the history of vulnology, much has been written; in Italy, we owe it mainly to Bonadeo and Guarnera, and I will limit myself to a quick outlook on ancient periods and civilizations (Table 1.1). Then, the story began, starting with the wound of Henry VIII Tudor (1491–1547), described in the annals of the time, and habits began to change with the arrival of Ambroise Parè (1510–1580). Surgeon Henry II of France reintroduced the ligation of the vessels in amputations and abandoned the use of cauterium replacing it with dog oil. (Take a liter of rose oil. Put four newborn dogs and earthworms. Bring to a boil until the flesh detaches from the bones. Excellent revulsant and to promote the suppuration of wounds). In 1551, he wrote the famous text “La manière

Fig. 1.7  Frida Kahlo, 1944, La Columna Rota (the broken column), original painting at the Museo Dolores Olmedo, Xochimilco, Mexico City, Mexico (figure under public domain)

de traiter les plajes,” with numerous illustrations for prostheses. Followed by Cesare Magati (1579–1647) who with the De rara medicatione vulnerum in two volumes published in 1616 began a new era. Starting from 1800, with Lister we enter the modern medicine that has evolved to the present day and that will be the task of the subsequent chapters to analyze, with the transition to the wet microenvironment and advanced dressings with winter, to the wound bed preparation of Falanga and Sibbald of the eighties up to the time currently applied with the developments that are currently in use.

E. Ricci and M. Pittarello

8 Table 1.1  Vulnology in the history of medicine Civilization Mesopotamia

Source period 4000 and—331 BC


Codex Hammurabi, seventeenth century BC 3000 BC


Smith Papyrus 1600 BC Ebers Papyrus 1550 BC Hearst papyrus circa 2000 BC 2000 BC–135 AC

Leviticus Bible Isaiah Bible Magna Graecia

Alcmeon of Crotone VI century BC Ippocrate 460 and—331 BC

Magna Graecia (continued)

Aristoteles 384 BC–322 BC

Data Knowledge of herbs and poultices “Pulverize pears and manna, mix with beer bottom and apply on the sick part” “Shred the roots of plants and snake skin, pour into boiling water and wash the diseased part” If a doctor treats a free man for an ulcer and the patient dies, the doctor will have his hands cut off Prosthesis of a big toe found on female mummy, articulated, and with signs of wear 48 cases of traumatic injuries Various cases including skin diseases 260 recipes including abscesses and paterecci Medicine is reserved for priests, the Levites Here, the concept of health or illness joins the divine with the concept of reward and punishment (parable of job) Inspection of sores and removal of lepers The wounded cannot offer to the god 38:21 Isaiah said, “take a poultice of dried figs, apply it to the ulcer, and the king will heal” The theorization begins that man is the microcosm, and the body is formed by the four fundamental elements, in order air, fire, earth, and water School of Kos, where clinical observation and semeiotics take shape, the focus will shift definitively to Greece Diseases originated from an imbalance of the four humors of the human body: Blood, phlegm, white bile, and black bile, which combined in different ways lead to health or disease (humor theory) The technique of bandages was very detailed; these were carefully sterilized, washed with soap and hot water, and dried in the sun It proposes a first rudimentary method of compression through the usage of sponges for the treatment of venous ulcers “In the presence of an ulcer it is not advisable to stand, especially if it is located on the leg We must avoid wetting any ulcer except with wine unless it is in close proximity to a joint, since the dry is closer to the healthy and the wet to the unhealthy” (varicose vein–ulcer ratio) He taught how to cauterize wounds He taught how to reduce and immobilize fractures He taught to incise abscesses On his advice, Alexander the great sent an entire army to conquer the island of Socotra, near the horn of Africa. This was to obtain the aloe crops used for the healing of wounds of men and horses In his “history of animals,” he mentions propolis, considered a useful remedy in skin diseases, ulcers, and suppurations He proposes poultices, remedies based on bran, water, and mustard, which gave relief to joint inflammation and cured infections

1  Vulnology (Also Known as Wound Care): History and Myths of Chronic Wounds


Table 1.1 (continued) Civilization Ancient Rome

Source period

282 BC Arcagato II sec BC Celsus 25 BC–About 45 AC

Scribonio largo first half first century AC Galen 129–201


Avicenna 980–1037


From V century AC

Data From ancient times when the pater familias was responsible for health, with Caesar begins a path that, following the Greek tradition, will first come to identify doctors and care facilities in the military, and then later extend to civilians with medical tabernae The first temple to Asclepius is founded on the Tiber Island, functioning as a protohospital In 219, he arrived in Rome, and the term vulnology is dedicated to him Writes the “De Medicina” first great medical text Write down the signs of inflammation: Rubor, tumor, Calor, dolor. Talks about ulcers in book IV In book V, he describes medicaments including hemostatic, suppurative, excoriate (healing), those designed to drop the crust, to smooth the sourness, and to make meat. “It stops any suppuration, a mixture of galbanum, crushed broad beans, myrrh, incense, bark of the root of the caper. It is also valid to dissolve the abscesses, the oyster lime, burned and pulverized, and then diluted in vinegar.” in the second part, it deals with wounds, defined as external, and it differentiates them according to the severity in easy, difficult, and incurable, considering the depth and vastness of the wound and the part of the body where it occurred. Describes the pus. Next, it shows how to stop bleeding with the help of gauze and how to heal the wound by suturing, buckles, or bandages. Defines amputation for gangrene In book VII, he provides plastic rudiments for amputations and ligation of varicose veins He used torpedoes for various therapies including ulcers that did not heal (hence torpid ulcers) Strong proponent of humoral theory, anatomist He studied the wounds of gladiators and noted that the nerve injury caused numbness He did not use bandages, supporter of enemas, and purgants His medical canon survived for over 700 years He hypothesized the presence of microorganisms in infections Occlusive treatments with silver and gold foils were initiated The concept of antisepsis began Based on the philosophy of the Celtic area, therefore of druidic shamanic competence, they based the concept of wound as a loss of soul parts, therefore, to be sought through the journeys of the curators Extensive use of fire, not only to cauterize and stop bleeding, but also as a moment of transformation as one of the four founding elements of matter

References 1. Ricci E.  Archagathus history’s first wound expert. EWMA J. 2013;1:38–9. 2. Hist GN, XXIX, 6, 12–13. 3. Buck RW.  Arcaghagathos: rephugee physicians and roman consul. N Engl J Med. 1952;246:866–7. 4. Bonadeo P, Rolandi M. Arcagatus: carnifex or victim? Acta Vulnol. 2014;12(1):1–11. 5. Andorlini I, Marcone L.  L’apporto dei papiri alla conoscenza della scienza medica antica. ANRW II. 1993;37(1):462–3. 6. Bonadeo P, Guarnera G. Skin sores, a story with many stories, a journey through time. Ed. Medea, 2019.

7. Ricci E.  Vulnology. The origin of the name. Acta Vulnol. 2010;8(2):59–60. 8. Bonadeo P.  Vulnology a name and its history. Acta Vulnol. 2013;11(1):9–14. 9. Harding K.  Woundology an emerging clinical specialty. Editorial. Int Wound J. 2008;5:597. 10. Ferrari A.  Dizionario di mitologia. Litopres, UTET, 2015. 11. Guidorizzi G. Il mito greco—gli dei. Ed. Mondadori, 2009. 12. Pindaro “Pitiche”. 3.5. 13. Genovese G. The myth of Philoctetes, an anti-heroic model and an intercultural archetype between East and West. Atti Accademia dei Lincei. 2001. 14. Holy Bible. Ed CEI 2008.


Aetiology, Classification and Advocating for a Holistic, Multidisciplinary Approach Alessandra Michelucci, Giammarco Granieri, Valentina Dini, and Marco Romanelli

2.1 Epidemiology Chronic wounds are characterised by an inability to heal within an expected period of time, although there are no prospective studies establishing the time frame to define an ulcer as chronic. Chronic ulcers represent a disease with a worldwide emotional and socio-economic impact [1–3]. Approximately 1–2% of the world’s population will develop a chronic ulcer during their lifetime. It is estimated that 6.5 million people in the United States alone are affected by chronic wounds [4, 5]. The incidence of chronic wounds varies with age, gender and geographical location. Limitations of epidemiological studies lie in the differences in the terminology used, as well as the difference in prevalence with age and geographic location and the high rate of recurrence after healing [6, 7]. Venous leg ulcers (VLUs), representing the most common form of ulceration of the lower extremities (80–90% of leg ulcers), have an average prevalence of 2.2 cases per 1000 persons. They are more common in the elderly population and in females. The prevalence and incidence double in patients >65 years of age [8–11]. A. Michelucci · G. Granieri · V. Dini M. Romanelli (*) Department of Dermatology, University of Pisa, Pisa, Italy e-mail: [email protected]

The prevalence of pressure ulcers (PUs) from cross-sectional studies presented in the literature ranges from 3% to 31%. They predominantly affect a population with low mobility, and the prevalence is influenced by the age and status of the patient (assessable by the Norton scale and the Braden scale) and the structure of residence (hospital, community and nursing homes) [12–16]. The risk of a patient with diabetes to develop diabetic foot ulcers (DFUs) during their lifetime is on average of 19–34% [17–19]. Worldwide DFU prevalence is 6.3%, and it is influenced by structure of residence, age, sex, diabetes type, region and other diabetes-related comorbidities [6, 20, 21]. Subjects with a DFU are >10 times more likely to have a lower extremity amputation (LEA) and a higher risk of death compared to healthy people [22, 23].

2.2 Aetiopathogenesis The physiological healing process consists of several sequential and overlapping phases, namely haemostatic, inflammatory, proliferative and remodelling phases [24]. In chronic ulcers, this linear succession of phases is lost and the different phases follow each other without a specific time frame [25, 26]. The role of the inflammatory phase in the tissue healing process is widely recognised. The inflammatory phase is generally

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



A. Michelucci et al.

followed by the proliferative phase, in which the the clinician to evaluate the complexity of the immune response moves towards an anti-­ patient’s condition. inflammatory and proliferative stage, which is Based on the clinical manifestations of chronic essential for the tissue repair process. Chronic venous disease, six distinct stages can be identiwounds, on the other hand, present a dysregula- fied: telangiectasias (C1), varicose veins (C2), tion of the inflammatory response that prevents oedema (C3), dystrophic lesions (C4), the presprogression to the next healing phase. In addi- ence of outcomes (C5) or an ongoing ulcer (C6) tion, distinct areas of the chronic ulcer may be at [30]. different healing stages, thus complicating the The pathophysiology leading to venous hypertherapeutic approach. Wound debridement aimed tension is complex and multifactorial, involving at synchronising the various areas of the wound genetic predisposition, environmental factors, at the same healing phase. The pathophysiology hormones, endothelial dysfunction, inflammais complex and multifactorial, involving genetic tory cells and molecules, as well as imbalances of predisposition, environmental factors, hormones, cytokines and matrix metalloproteinases [31]. endothelial dysfunction, dysregulation of the For a proper management of such a debilitatimmune response, and both innate and specific ing disease, the therapeutic approach, largely alterations of vascular endothelium, as well as based on elasto-compression, must be initiated in imbalances of cytokines and matrix metallopro- the early stages of the disease and must be folteinases (MMPs). lowed by an adequate territorial and home management of the patient. The characteristics of VLUs reflect their 2.3 Classification patho-physiological features, with the involvement of perforant vein between the deep and Chronic ulcers are classified according to their superficial circulation and the occurrence of heterogeneous aetiology into vascular ulcers venous hypertension [32, 33]. VLUs are typically including those due to venous insufficiency, arte- superficial and affect the medial supramalleolar rial insufficiency, vascular mixed aetiology, dia- region. The wound bed is usually red or yellow, betic ulcers, pressure ulcers and atypical ulcers. due to the presence of fibrin, and presents a large amount of exudate. The wound edges have irregular shape, and perilesional skin presents signs of 2.3.1 Venous Ulcers chronic venous disease (oedema, varicose veins or lipodermatosclerosis). Pain is not generally Chronic venous disease (CVD), afflicting 2% of too intense and decreases by lifting the limb the population in Western countries, constitutes a [34–37]. significant socio-economic burden on the healthcare system due to the strong psychophysical impact on the affected individual [27]. 2.3.2 Arterial Ulcers The internationally accepted classification system for approaching the complexity of chronic Arterial ulcers typically involve the lateral survenous disease is identified by the acronym face of the lower limb and the distal extremity Clinical-Etiology-Anatomy-Pathophysiology (back of the foot and toes). On objective exami(CEAP). nation, it is possible to identify a reduction of the Developed in 1993, updated in 1996 and peripheral pulses (dorsal pedidium or posterior reviewed in 2004, CEAP is a classification sys- tibial), which can be confirmed by colour Doppler tem based on our current knowledge of clinical examination. Clinically, they appear as smaller manifestations, aetiology, anatomy and underly- size ulcers but with greater extension in depth ing venous pathology [28, 29]. Each parameter is compared to venous ulcers, sometimes involving subclassified into several groups, which allows tendon and bone. Symptomatology is intense and

2  Aetiology, Classification and Advocating for a Holistic, Multidisciplinary Approach

increases as the limb is lifted. The wound bed often has necrotic adhered tissue. The wound edges are regular (punched-out appearance). The perilesional skin shows signs of atrophy with a pale appearance and loss of hair follicles [38].

2.3.3 Diabetic Foot Ulcers DFUs, depending on the main pathogenetic mechanism, may be neuropathic, ischaemic or neuroischaemic [38]. Neuropathic diabetic ulcers are located in areas of increased pressure, at the plantar surface of the foot and above the metatarsal regions. The presence of the callus in pressure areas increases the risk of pressure at the level of the foot. Charcot’s foot is typically found in neuropathic diabetic ulcers as a consequence of bony deformation, resulting from the inflammatory process [39, 40]. Neuropathic diabetic ulcers, on the other hand, present similar characteristics to those originating from arterial insufficiency. The basic pathogenetic mechanism is in fact the ischaemic process. The wound bed is frequently necrotic, and the perilesional skin reveals signs of atrophy. When these ulcers increase in size, they may involve a large portion of the foot with increased risk of over-infection and amputation [39]. Diabetic neuroischaemic ulcers combine the characteristics of the two previous types.

2.3.4 Pressure Ulcers PUs are nowadays more properly called pressure injuries, mainly involving skin regions located above bony prominences, i.e. the heel, hips, occiput and sacral region. They result from the combination of pressure and traction forces at the affected site, in patients generally with reduced mobility or immobility [41]. According to the latest National Pressure Ulcer Advisory Panel (NPUAP) classification, different stages of pressure injuries can be identified. The first stage is characterised by non-blanchable erythema. The second stage involves the dermis, while the third stage reaches the subcutaneous tissue. When ten-


dons and bones are involved, the fourth stage is defined. Recently, two other stages are described: an unstageable full-thickness pressure injury, in which the real extent of tissue loss cannot be confirmed because it is obscured by slough or eschar, and deep tissue pressure injury with a persistent and non-blanchable deep red, brown or purple discoloration [42]. The growing interest in these kinds of wounds is related not only to the high incidence in hospitalised patients or residents of RSAs but also to the possibility of prevention by means of appropriate anti-decubitus devices [43].

2.3.5 Atypical Ulcers Atypical ulcers include on average 20% of all chronic wounds and are characterised by atypical parameters regarding location, clinical features and aetiology [44]. They are usually caused by immunological dysregulations (such as pyoderma gangrenosum), micro-occlusion of blood vessels in the lower limbs (mainly due to intravascular thrombi, embolization or coagulopathies), vasculitides of small and medium vessels, ischaemic arteriolosclerosis (Martorell’s hypertensive ischaemic leg ulcer (HYTILU) and calciphylaxis), primary skin tumours or metastases to the skin, infection and artefactal ulcers. In less developed countries, aetiologies also include nutritional deficiencies, chronic parasitic and fungal infestations and leprosy. If a wound has an abnormal presentation or location, causes severe pain compared to size and fails to heal within 12  weeks of standard treatment, an atypical wound can be suspected and must be confirmed through a skin biopsy [45, 46].

2.4 Diagnosis Chronic ulcers present a wide heterogeneity according to their aetiology, pathogenesis, appropriate management approach and prevention. The objective examination of the patient focuses on the assessment of the site and the clinical features of the lesion, i.e. the wound bed, the edges and the perilesional skin. A clinical evaluation of the


patient’s general clinical condition and past medical and pharmacological history must be carried out. Finally, physical examination, including the evaluation of peripheral arterial pulses and the identification of other clinical signs suggestive of underlying pathology, must be performed. The ankle-brachial pressure index (ABI) is measured by dividing the systolic ankle pressure by the systolic brachial pressure. Normal values are considered 1.0 and 1.1, while values  75%, or lesions T4, I4, M4, and E4 with 100% of necrotic tissue infections, exudate, and the absence of spontaneous new epithelialization: With the same situation, in any case, the choice of therapy will change the history of the lesion and the timing of healing.

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,


C. Ligresti

54 Table 6.1  Soft: not aggressive treatment T Non-viable tissue

Absent 0

Present 1 25%

Present 2 50%

Present 3 75%

Present 4 100%

I Infection or inflammation

Absent 0

Present 1 Contamination

Absent 0

Present 1 Low

E Delay of Epidermization

Absent 0

Present 1 25%

Present 2 50%

Present 3 Critical Colonization Present 3 Abundant and Color Present 3 75%

Present 4 Infection

M Exudate And maceration

Present Critical 2 Colonization Present 2 Abundant

For exemple, choising a soft treatment [such as autolysis, we have a significant improvement of the lesion as low as 25 days [21–23]. This time can decrease, even drastically, by level up in the type of strategy used: The time passes to 20 days with osmosis, 15 days with the larvae, until a day using hydrotherapy, ultrasound, or surgery. Regarding the I: We passed from an improvement of 55 days with saline [strategy blander], to 21  days of antiseptics/dressings with silver/ NPWT [negative pressure wound therapy] up to 7  days after the surgery/ antiseptics/antibiotics/ NPWT. The M represents an increase in 55 days with hydrogel/hydrocolloid and hydrofiber 28  days with up to 10 days of the surgery. Finally, the E: new epithelialization from 100 days with advanced medications, 45 days with VAC and only 10 days with autologous graft [24]. Time of Healing: The numerical value is in direct relation to the selected therapy. It is equal to that of IG patient, and its value will not change if the therapy choice [soft] is on the left side of the table therapeutic. MA: medium-aggressive treatment; A: aggressive treatment report of the results obtained with the averages of the healing times on a number of 22 patients, obtaining a slightly higher percentage of error of 10% in the prediction of healing time. Our protocol GI is 50 and ASA 50, and ASA is 4–5 with infection between 1 and 2 as soft

Present 4 Abundant, color and smell Present 4 100%

therapy. GI is >50 and ASA is 4–5 with infection between 3 and 4 as medium aggressive therapy. Nowadays, various systems try to give a prediction of healing time, taking into account various parameters. Troxler et  al. [20] studied the importance of periodic evaluations of the wound, accompanied by measurements of its surface, for the identification of potentially hard-to-heal wounds. The early detection of a reduction in the size of the wound is set by measuring the progress of the margin [epithelial advancement]. Phillips et  al. considering the percentage reduction in venous ulcer area found that in about 77% of cases, healing outcomes could be predicted based on a wound size reduction of more than 44% at 3 weeks. We are able to show that for venous leg ulcers, a simple rating system score based on size and duration can give a good indication of the likely outcome at 24 weeks. Falanga et al. incorporated measurement of epithelial advancement into a scoring system on the healing of venous leg ulcers. This system [wound bed score] also examines other characteristics including the extent of skin dermatitis around the wound, the presence of eschar, callus, and/or fibrosis around a wound, pink, or red wound bed, exudate, and the volume of the edema (Table 6.2). The complexity of the wound is likely to exert a significant influence on the progression of the healing process, and the factors that combine to deter-


6  The TIMEH Protocol Table 6.2  Size of the wound ( WS: small, WM: medium, WL: large, WXL: extra large, WXXL: extra extra large) SIZE – volume W Score W

300 cm3 WXXL 32

Table 6.3  Level of pain Table pain


No = 1

Little = 2

Much = 3

Table 6.4  Risk factors

1 2 3 4 5

GC: General condition of the patient GC score calculation Indicators Major 80 years old Lack of nutrition Preparing diseases Not self-sufficient ASA – Anesthesiological risk index 3–4

mine it can be classified into four main groups: patient factors, factors related to the wound, knowledge of the HCP, factors, and resources related to the treatment. In a study by Margolis et  al. on a group of patients with venous ulcers, it has emerged a correlation between some specific characteristics of the wound and the healing process: wound duration, size, and depth of the wound. Ulcer size [>2 cm2], the duration [>2 months], and depth [penetration through exposed tendon, ligament, bone, or joint] were the three most important factors for predicting the outcome. Patients with all three factors had only a 22% chance of healing by 20 weeks (Table 6.3). For the physiological nature of the healing process, it is inevitable that large wounds will require more time to heal than smaller wounds. In addition, the longer a wound remains open, the greater the risk of complications, such as infections, is present. Therefore, a treatment that reduces the size of the wound and the infection risk is able to offer potential benefits. The presence of necrotic tissue in a wound has been for a long time considered an obstacle to the evaluation of the lesion, as well as a potential predictive factor of delayed healing and a possible outbreak of infection (Table 6.4). In chronic wounds, there is a tendency for the inflammatory response [which is an important

NO = 0/SI = 2 2 2 2 2 2

element of the initial response to the lesion]. This results in increased production of pro-­ inflammatory cytokines, reactive oxygen species, and proteolytic enzymes [such as certain MMPs, elastase, and plasmin]. This activity is combined with a minor issue, for example, inhibitors TIMP (Table 6.5), and is further enhanced by alterations of pH at the level of the wound bed. Excessive activity of these enzymes causes not only deleterious extracellular matrix destruction, but also inactivation of growth factors. There is a correlation between the state of chronic inflammation of a wound, the high levels of protease exudate, and the slowdown in the process of tissue repair. The control of inflammation and the concentration of MMPs (metalloproteases) are essential, as the protease not only degrades the fabric, but also leads to the growth factors activity’s reduction. Gjødsbøl et al. found a significant link between diversity and the density of the bacterial species detected on the diagnostic buffer and the time required for wound healing. Also, the presence in a wound of specific bacterial species has been put in relation to the outcome of healing. For example, the presence of Pseudomonas aeruginosa in venous leg ulcers can delay healing. According to Mogford et  al., an ischemic wound is probably the most common cause of

C. Ligresti

56 Table 6.5  Environmental and behavioral factors of the patient EBF: environmental and behavioral factors of the patient Score Indicators Intake of corticosteroid drugs Taking anti-cancer drugs Taking anticoagulant drugs The patient has no assistance The patient lives in an unhealthy environment The patient lives alone The patient does not exercise any physical activity The patient smokes The patient drinks excess alcohol The patient has no scholarship

FAC 1° 2° 3° 4° 5° 6° 7° 8° 9° 10°

Yes = 1/no = 0 1 1 1 1 1 1 1 1 1 1 Max 10

Table 6.6  TIMEH protocol




Enzymes Larvae

Hydro therapy

Ultra sound


1 day

1 day

25 days

20 days

15 days

1 day

Physiological Solution Ringer

Local antiseptics

Antiseptic Silver Dressings

Antiseptic Silver Dressings VAC

55 days

40 days

35 days




21 days

Antiseptic Silver Dressings VAC Antibiotic 15 days

Surgery VAC

Surgery Antiseptic Silver Dressings VAC Antibiotic

12 days

7 days

Hydrocolloids Collagen Hyaluronic Hydrogel acid 45 days 55 days


Hydrofibers Poly urethane



35 days

28 days

21 days

15 days

10 days

Hydrocolloids Hydrogel Collagen Hyaluronic acid

Growth Factors Carboxy therapy

VAC Oxidized Regenerated Cellulose

Allo-Skin Graft Dermal substitutes

VAC Growth factors Dermal substitutes

Skin graft Flaps

90 days

60 days

45 days

35 days

non-healing. Because of poor perfusion, metabolic gas exchange at the level of tissues becomes inefficacious. It has been shown that the healing of a wound following surgery is compromised by dehydra-

25 days

10 days

tion and by a low body temperature of the patient, factors that are associated with reduced perfusion tissue and poor oxygenation (Table 6.6). Physical factors, such as diabetes mellitus, obesity, malnutrition, advanced age [over 60],

6  The TIMEH Protocol

decreased perfusion, peripheral vascular disease, cancers, organ failure, sepsis, and even restrictions on mobility, can affect the healing process. Marston et al. have found that improved glycemic control has a positive influence on the outcome of diabetic foot wounds, particularly when dermal substitutes are used. Terms of immunodeficiency, use of immunosuppressive drugs [corticosteroids, azathioprine, or methotrexate], and the presence of diseases [such as diabetes mellitus] known to affect the immuno-inflammatory response are all circumstances that may influence negatively healing and increase the risk of wound sepsis It was also found that psychosocial factors such as social isolation, gender, smoking, the economic conditions, and the experience of pain could influence wound healing. Stress and depression have been linked to changes in immune function and may therefore adversely influence a wide range of physiological processes, including wound healing. In a human experimental model, it was found that stress and depression had a possible role in the modulation of matrix metalloproteinases [MMPs] and expression of tissue inhibitors of metalloproteinases [TIMP]. According to some studies, also the ability to cope with stress is a factor that can influence healing times. Salaman et al. studied a group of 45 hospital patients with venous ulcers, 16 [36%] of who do not make satisfactory progress. Only half of these 16 patients said they had received any explanation about the cause of the ulcer and the treatment method used. This study raises important questions about the impact on wound healing of the patient’s beliefs and their confidence in treatment. Blunting is the case of patients who are indifferent to the processing and not very interested in the progress of the wound toward the healing. Although the feeling of helplessness is experienced by some patients, many of them make every effort to ensure that the care they receive meets their needs. Some patients become experts in their own condition, often using the Internet to gather information on it.


When a wound is located on a pressure-­ bearing surface or a mobile area such as around a joint, the choice of the material of the dressing and the method of attachment is of extreme importance. However, Chipchase et  al. observed that, while the overall healing rates of foot ulcers were similar, lesions located in the heel tended to heal more slowly. The authors concluded that the outcome was generally favorable, with 65.6% of heel ulcers healed in a median time of 200 days. Harding has the potential effect of fibroblast senescence on chronic wound healing. There was a correlation between the ratio of senescent fibroblasts/non-senescent fibroblasts and healing outcomes: An accumulation of more than 15% senescent fibroblasts is considered the threshold beyond which wounds will have trouble healing. Moreover, the response to treatment can be an indicator of tissue viability and healing potential. For example, it was suggested that a reduction in wound area of around 15% within 1–2 weeks of topical negative pressure therapy is a positive indicator of the likely evolution of the wound and that this observation can be the decision to continue therapy. As seen above, many attempts and proposals tend to quantify the time required for wound healing. On the basis of previous attempts, our aim is to propose an algorithm not only to accurate the quantification of healing time, but also a precise protocol of treatment to be associated with any situation and any type of wound. It is therefore clear, as the challenge of healing a skin lesion cannot be achieved by a single specialist. It is fundamental collaboration between various specialists. It is obvious that the planning therapy must be organized by a team leader to coordinate the rest of the medical staff [various specialists including plastic surgeon, vascular surgeon, the internist, the nutritionist, the endocrinologist, the dermatologist, etc.] and not by hospital nurses or domiciles medical figures. Only with careful collaboration and clearly careful training, you can pursue the goal in the shortest time possible and with the greatest patient comfort.


This protocol sets itself as a general guideline for the ulcer treatment for all types of professionals involved in the management of the patient but is particularly useful for those who approach the world of vulnology [wound treatment], but who do not yet have detailed knowledge about it. It appears a useful tool, and since for the first time, it offers a mathematical model in which a score is calculated and according to the same applies a type of therapy. In conclusion, the algorithm that we propose is a useful tool for staging the severity of injuries and provides a simple means to adjust therapy. It describes how the therapy used should change significantly according to the type and severity of the wound that we are facing and how this in turn can affect significantly the healing time estimated. It is clear that, not always, the mathematical calculations are an exact prediction, but allow, however, to have a prediction of the initial situation. There are margins of error, especially when it takes over factors that complicate the wound management. It is highly appreciated that, to predict the outcome of recovery in individual patients, it will be necessary to use not a single marker, but the data resulting from a combination of several markers, as we proposed. Many authors have stressed the importance of training the nursing staff, designed to provide the knowledge and skills necessary to establish appropriate treatment and process protocols and forms relating to wound care [25]. However, we can conclude by saying that we do not presume to have created a perfect model for the treatment of skin lesions, and we only want to provide a useful tool to the caregiver based on current knowledge and on current therapeutic strategies. We are still waiting for new knowledge that can lead us to an even higher level in the treatment of this complex disease [26].

References 1. Chase SK, Melloni M, Savage A. A forever healing: the lived experience of venous ulcer disease. J Vasc Nurs. 1997;15(2):73–8.

C. Ligresti 2. Kramer JD, Kearney M.  Patient, wound, and treatment characteristics associated with healing in pressure ulcers. Adv Skin Wound Care. 2000;13(1):17–24. 3. Franks PJ, Moffatt CJ. Do clinical and social factors predict quality of life in leg ulceration? Int J Low Extrem Wounds. 2006;5(4):236–43. 4. Moor AN, Tummel E, Prather JL, Jung M, Lopez JJ, et al. Consequences of age on ischemic wound healing in rats: altered antioxidant activity and delayed wound closure. Age (Dordr). 2014;36(2):733–48. 5. Margolis DJ, Berlin JA, Strom BL. Risk factors associated with the failure of a venous leg ulcer to heal. Arch Dermatol. 1999;135(8):920–6. 6. McGinnis E, Greenwood DC, Nelson EA, Nixon J.  A prospective cohort study of prognostic factors for the healing of heel pressure ulcers. Age Ageing. 2014;43(2):267–71. 7. Little MO. Nutrition and skin ulcers. Curr Opin Clin Nutr Metab Care. 2013;16(1):39–49. 8. Leymarie F, Richard JL, Malgrange D. Factors associated with diabetic patients at high risk for foot ulceration. Diabetes Metab. 2005;31(6):603–5. 9. Kiguchi MM, Hager ES, Winger DG, Hirsch SA, Chaer RA, et  al. Factors that influence perforator thrombosis and predict healing with perforator sclerotherapy for venous ulceration without axial reflux. J Vasc Surg. 2014;59(5):1368–76. 10. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219–29. 11. Costa A, Cunha M. Prevalence of pressure ulcers in person victim of trauma: predisposing factors. Servir. 2013;58(1–2):60–77. 12. Abbade LP, Lastória S, Rollo Hde A.  Venous ulcer: clinical characteristics and risk factors. Int J Dermatol. 2011;50(4):405–11. 13. Ahmad W, Khan IA, Ghaffar S, Al-Swailmi FK, Khan I. Risk factors for diabetic foot ulcer. J Ayub Med Coll Abbottabad. 2013;25(1–2):16–8. 14. Baba M, Davis WA, Davis TM.  A longitudinal study of foot ulceration and its risk factors in community-­based patients with type 2 diabetes: the Fremantle diabetes study. Diabetes Res Clin Pract. 2014;106(1):42–9. 15. Astudillo B, Cruz M, del Prado L, Domenack R, Nasi E, et al. Profile of patients admitted with infected skin ulcers at Bella Vista Hospital Mayagüez. Bol Asoc Med P R. 2013;105(3):29–35. 16. Haji Zaine N, Burns J, Vicaretti M, Fletcher JP, Begg L, et  al. Characteristics of diabetic foot ulcers in Western Sydney, Australia. J Foot Ankle Res. 2014;7(1):39. 17. Huliev D.  Obstacles in wound healing. Acta Med Croatica. 2013;67(Suppl 1):5–10. 18. Raju D, Su X, Patrician PA, Loan LA, McCarthy MS.  Exploring factors associated with pressure ulcers: a data mining approach. Int J Nurs Stud. 2014;52(1):102–11. 19. Peghetti A, Mantovani M, Canova G, Ferri L.  Le medicazioni avanzate per il trattamento delle ferite

6  The TIMEH Protocol acute e croniche. Dalle evidenze della letteratura alla pratica quotidiana. Commissione Regionale Dispositivi Medici Reg Emilia Romagna, 2012: 1–126. 20. Bailey MA, Mc Pherson SJ, Troxler MA, Peach AH, Patel JV, et  al. Ischemic skin ulceration complicating glue embolization of type II endoleak after endovascular aneurysm repair. J Vasc Interv Radiol. 2011;22(2):163–7. 21. AISLeC. Profilassi delle lesioni da decubito e cambio posturale: ricerca multicentrica. AISLeC; 1995. 22. Bateman S. Principles of preventative foot care. Br J Community Nurs Suppl. 2014;S30(S32–4):S36–8.

59 23. Gantwerker EA, Hom DB. Skin: histology and physiology of wound healing. Facial Plast Surg Clin North Am. 2011;19(3):441–53. 24. Registered Nurses Association of Ontario Risk Assessment and Management of Pressure Ulcers; 2011. 25. Hien NT, Prawer SE, Katz HI.  Facilitated wound healing using transparent film dressing following Mohs micrographic surgery. Arch Dermatol. 1988;124(6):903–6. 26. Ligresti C, Bo F.  Wound bed preparation of difficult wound: an evolution of principles of TIME.  Int Wound J. 2007;4(1):21–9.

Part II Dressing and Bandages


Ulcer Debridement Tedeschi Pasquale and Michele Maruccia

7.1 Debridement Overview Wound management is a crucial aspect of health care, particularly for patients who have experienced chronic wounds or non-healing ulcers [1]. Wound bed preparation is a fundamental aspect of this process, which involves creating an optimal environment for the wound to heal. Achieving a clean, moist, warm, and granular wound bed is essential for promoting healing and protecting the periwound and intact skin. Debridement, bacterial control, and exudate management are all critical components of wound bed preparation [2]. At its core, debridement is the process of removing necrotic tissue, foreign material, and debris from the wound bed. This procedure is vital for wound management and serves several purposes: • Decreasing bacterial concentration. • Increasing the effectiveness of treatments. • Improving leukocyte activity. • Shortening the inflammatory phase.


T. Pasquale (*) · M. Maruccia Division of Plastic and Reconstructive Surgery, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, Bari, Italy

• Freeing up energy for wound healing. • Removing barriers for healing. • Decreasing wound odor. Debridement is essential in cases where necrotic tissues, foreign materials, or debris are present within the wound bed [3]. Large blisters and calluses should also be debrided to promote optimal healing. However, it is important to note that not all wounds are suitable for debridement. Three primary contraindications exist for this procedure. Firstly, red granular wounds should not be debrided, as this tissue is essential for healing. Secondly, non-infected ischemic wounds are contraindicated for debridement, as they lack the necessary blood supply for optimal healing. Lastly, current guidelines suggest that stable heel ulcers with dry eschar should only be debrided if they have edema, erythema, fluctuance, or drainage [4, 5]. There are six primary types of debridement: autolytic, enzymatic, biological, mechanical, sharp, and surgical debridements. Autolytic debridement involves the use of a moist wound dressing to encourage the body’s natural enzymes to break down necrotic tissue. Enzymatic debridement utilizes topical enzymes to break down necrotic tissue, while biological debridement involves using maggots to remove necrotic tissue. Mechanical debridement uses physical force to remove debris and necrotic tissue, while sharp debridement involves using surgical tools to

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



remove necrotic tissue. Lastly, surgical debridement involves removing necrotic tissue through surgical intervention [6, 7]. When deciding on the most appropriate debridement method, clinicians should consider the patient’s clinical condition, the type of wound, the location of the wound, and the amount of necrotic tissue present. Additionally, patients’ pain levels, comorbidities, and cognitive status should also be considered when selecting the most appropriate debridement method [8].

7.2 Autolytic Debridement Autolytic debridement is a type of wound debridement that uses the body’s own natural enzymes to break down and remove necrotic tissue from a wound. This process occurs when a moistureretentive dressing is applied to the wound, which keeps the wound bed moist and allows the body’s enzymes to work more effectively. In more detail, the moist environment created by the dressing helps to activate enzymes called proteases that are naturally present in the wound bed. These proteases break down the proteins that make up necrotic tissue, making it easier for the body to remove it through the normal healing process [9]. One example of a dressing that is commonly used for autolytic debridement is a hydrocolloid dressing, which is designed to absorb excess moisture from the wound and create a moist environment. Other types of moisture-retentive dressings, such as hydrogels and foams, may also be used depending on the specific needs of the wound [10]. Eschar (hardened or dead tissue) should be crosshatched; this will aid in promoting the circulation of fluids and enzymes during autolytic debridement. The moisture-retentive dressing should be applied to the wound and should extend at least 2 cm beyond the edges of the wound to ensure a proper seal. The periwound area should also be protected to prevent damage to the surrounding healthy tissue. Finally, signs and symptoms of infection should be carefully monitored to ensure that the wound is healing properly.

T. Pasquale and M. Maruccia

Autolytic debridement is considered to be the most conservative, least invasive, and least painful method of debridement. It is also easy to teach to patients and caregivers, and it may reduce the long-term cost of treatment. However, it is important to note that autolytic debridement requires time for the body to naturally debride tissue, and it does not allow frequent visualization of the wound bed. Autolytic debridement is indicated for non-­ infected wounds with necrotic tissue, patients who cannot tolerate other forms of debridement, and home or long-term care settings. It is not appropriate for infected or deep cavity wounds and wounds that require sharp or surgical debridement. If necrotic tissue fails to decrease in the expected amount of time, other types of debridement should be considered. In conclusion, autolytic debridement is a natural and effective way to remove necrotic tissue from wounds. By creating a moist environment that supports the body’s natural healing processes, autolytic debridement can help promote healthy tissue growth and speed up the healing process. With proper patient selection and wound care, autolytic debridement can be a valuable tool for managing non-infected wounds with necrotic tissue.

7.3 Enzymatic Debridement Enzymatic or chemical debridement refers to the use of a topical enzyme to remove devitalized tissue. It is a form of selective debridement that utilizes the body’s natural enzymes or artificial enzyme preparations to digest necrotic tissue. The three main types of enzymes used for enzymatic debridement are proteolytics, fibrinolytics, and collagenases [11]. Proteolytic enzymes such as papain and bromelain break down proteins in the necrotic tissue, while fibrinolytic enzymes such as streptokinase and urokinase dissolve fibrin clots in the wound bed. Collagenase, on the other hand, is used to break down collagen in the wound bed, which helps to loosen and remove necrotic tissue (Fig. 7.1) [12, 13].

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Fig. 7.1  Enzymatic debridement using bromelain-based ointment on a deep burn wound. (a) Pre-debridement: A photograph of the deep burn wound of thorax and abdomen before enzymatic debridement. (b) Application of enzymatic ointment: The enzymatic ointment is applied to the burn wound. The ointment contains proteolytic enzymes that selectively target and break down necrotic

tissue, facilitating the removal of nonviable material. (c) Post-­debridement: Following enzymatic debridement, the burn wound shows significant improvement. Necrotic tissue has been effectively removed, revealing a clean wound bed. The wound appears more viable and is better prepared for subsequent wound management and healing interventions


Collagenase-impregnated gauze or ointment is applied directly to the wound bed and covered with a secondary dressing to maintain a moist environment. The dressing must be kept moist to maximize the enzymatic activity and therefore may require frequent dressing changes [11]. Enzymatic debridement is considered less invasive and less painful than other methods of debridement, except for autolytic debridement, which also uses the body’s endogenous enzymes to remove necrotic tissue. It requires less advanced technique than sharp or surgical debridement and is easy to instruct patients and caregivers to perform. However, enzymatic debridement can be expensive and may require dressing changes up to three times a day. This kind of debridement is appropriate for those who cannot tolerate sharp debridement, home or long-term care settings, and infected and uninfected wounds with necrotic tissue. It is especially useful for wounds that are difficult to access, such as deep cavities or wounds in the feet. Enzymatic debridement may also be used as a precursor to sharp debridement to reduce the amount of necrotic tissue in the wound bed and make it easier to perform the procedure. Enzymatic debridement is not appropriate for facial wounds, calluses (since enzymes cannot debride calluses), wounds free of necrotic tissue, and wounds with exposed deep tissues including tendons, blood vessels, and ligaments. If necrotic tissue fails to decrease in the expected amount of time, other types of debridements should be considered.

7.4 Biological Debridement Biological debridement is a unique form of debridement that involves the use of live medical devices, specifically maggots. These tiny larvae have been used for centuries to treat wounds and, more recently, have been recognized as a legitimate medical treatment. The process involves placing maggots onto the wound bed, where they produce and release enzymes that break down the necrotic tissue. What is remarkable is that they do this without

T. Pasquale and M. Maruccia

harming the surrounding viable tissue. Additionally, they ingest the dead tissue and bacteria, further assisting in the debridement process. Studies have shown that maggots are more effective at debriding wounds than some other debridement methods, making them a viable option for wound care. However, it is important to note that biological debridement may not be suitable for all patients, particularly those with a weak immune system or those with an allergy to maggots [14]. While the thought of using maggots for wound care may seem unorthodox, it is worth considering given its effectiveness and relative affordability. It is important to discuss the benefits and risks with a healthcare professional before making any decisions regarding wound care.

7.5 Mechanical Debridement Mechanical debridement is a process of removing devitalized tissue, foreign materials, and debris from a wound bed through the application of physical force. This form of debridement is usually performed using simple techniques that are easy to learn and perform, and it can be used in a wide range of wound care settings. However, it is important to note that mechanical debridement is nonselective and can potentially damage healthy tissue, which makes it unsuitable for some types of wounds [15]. There are several methods of mechanical debridement, including wet-to-dry dressing, hydrophobic dressing, and scrubbing. Wet-to-dry dressings are commonly used for the debridement of necrotic wounds. This involves applying saline-moistened gauze to the wound bed, which is allowed to dry. The dressing is then removed, along with any necrotic tissue that adheres to it. However, this method has several disadvantages. Viable tissue can adhere to the gauze and be traumatized on removal. The wet-to-dry procedure can also cause wound bed desiccation and periwound maceration, making it unsuitable for wounds with granular tissue [16, 17].

7  Ulcer Debridement

Hydrophobic dressings are another type of mechanical debridement that can be effective in removing bacteria from infected wounds. These dressings are coated with a fatty acid derivative that makes them highly hydrophobic. Bacteria are attracted to the dressing in the moist environment of the wound and become irreversibly bound to it. When the dressing is removed, the captured bacteria are also removed, preventing them from multiplying or escaping while in contact with the dressing [18]. Scrubbing is a nonselective form of mechanical debridement that involves using a sponge, brush, or gauze with water saline to clean the wound bed. This method can be effective in removing debris and necrotic tissue, but it can also potentially traumatize healthy tissue within the wound bed. As a result, scrubbing may be contraindicated for granulating wounds. Mechanical debridement is a useful tool for wound care providers, particularly in settings where access to more advanced debridement techniques is limited. However, it is important to use mechanical debridement carefully and only in appropriate cases to prevent further damage to the wound bed. This is particularly important in the case of wounds with granulation tissue, where mechanical debridement may be too harsh and cause further damage. In such cases, more selective methods of debridement, such as enzymatic or surgical debridement, may be more appropriate.

7.5.1 Wound Irrigation Wound irrigation is a procedure that uses saline or another prescribed liquid in a syringe to wash out excessive discharge, debris, and bacteria from an open wound. The pressure applied should be sufficient to reach the desired area, typically applied manually. The type of solution to be used, the desired strength, and correct temperature should be selected carefully. Wound irrigation facilitates debridement, assists with maintaining a moist wound environment, and enhances wound healing. The procedure is simple, quick, inexpen-


sive, and effective. Irrigation can be easily performed on any location on the body and in any treatment setting. Disadvantages of wound irrigation include the potential for irrigant runoff to soil linens or clothing. Wound irrigation is an acceptable intervention for all types of wounds, especially for healing granular wounds, but is not indicated for active, profusely bleeding wounds [19, 20].

7.5.2 Pulsed Lavage Pulsed lavage (pulsatile lavage) is the delivery of a wound irrigant under pressure by an electrically powered device to assist in debridement of necrotic and infected tissues [21]. It enhances granulation tissue formation, epithelialization, and local tissue perfusion. The goal is to remove unwanted tissue without disturbing healthy tissue. Pulsed lavage involves regular, automatic interruption of fluid flow with a handheld device to regulate irrigation pressure. Normal saline is the most commonly used irrigating solution, and antibiotics can be added to the irrigation fluid to help reduce the wound’s bioburden. A pressure of 4–15  psi is considered [22]. Pulsed lavage has several advantages, including portability, shorter treatment times, lower cost, less risk of cross-­ contamination, and less patient stress. However, it is not appropriate for extensive wounds. Pulsed lavage is indicated for cleansing or debriding a variety of wounds, including venous, pressure, and neuropathic ulcers. Pulsed lavage is also appropriate for tunneling or undermining wounds. No absolute contraindications exist when a psi of 15 or less is used. However, pulsed lavage should not be used in body cavities, on facial wounds, on recent grafts, or on actively bleeding wounds. It should be used with caution on patients taking anticoagulants, insensate patients, and deep tunneling wounds. Irrigation with greater than 15 psi is contraindicated. When pulsed lavage is performed, both the patient and clinician should wear appropriate barrier devices due to aerosolization [23].


T. Pasquale and M. Maruccia

7.6 Sharp Debridement

7.7 Surgical Debridement

Sharp debridement is a type of wound debridement that involves the use of sharp instruments, such as forceps, scissors, or scalpels, to selectively remove nonviable tissues, foreign materials, and debris from the wound bed. This technique is the fastest and most aggressive form of debridement outside of surgery and is typically performed by physicians, podiatrists, nurses, and physical therapists. Sharp debridement is indicated for several conditions such as advancing cellulitis or sepsis, necrotic tissues, eschars, calluses, or chronic wounds [24]. Examples of wounds that can benefit from sharp debridement include pressure ulcers, venous ulcers, diabetic foot ulcers, and surgical wounds. Sharp debridement is also used in burn wound care to remove eschar and promote healing. The mechanism of action of sharp debridement involves the physical removal of nonviable tissue, debris, and bacteria from the wound bed. This promotes the formation of healthy granulation tissue and enhances the wound’s ability to heal. Sharp debridement also helps to reduce the bacterial load and prevent the spread of infection to surrounding tissues. In addition, it allows for better visualization of the wound bed, which helps clinicians to identify signs of infection or other complications [25]. It is important to note that sharp debridement should not be performed if the material to be debrided is unidentified, pain is not adequately controlled for the patient, or the clinician’s competency is lacking. It is also not indicated for non-infected ischemic ulcers without adequate perfusion. Furthermore, sharp debridement should be used with caution on patients who are thrombocytopenic or those on anticoagulants. During sharp debridement, scalpels and scissors should be applied parallel to the wound surface. The wound is debrided in layers, starting with the most superficial layers, and rinsed with saline to remove any remaining debris. After debridement, the wound is reassessed for signs of infection or other complications.

Surgical debridement is a method of wound debridement that involves the use of surgical instruments such as scalpels, scissors, or lasers in a sterile environment to remove nonviable tissues from the wound bed. It is a fast and aggressive method of debridement that is performed by a physician or podiatrist who has advanced knowledge, skill, and training in surgical procedures. Unlike other forms of debridement, surgical debridement requires the use of anesthesia due to the length of time required to debride the wound and/or the extent of debridement required (Fig. 7.2) [26]. The goal of surgical debridement is to remove all nonviable tissue from the wound bed, including necrotic tissues, foreign materials, and debris. This is achieved by excising nonviable tissues along the margin of healthy tissue and by exploring the wound to debride deeper structures such as infected bones or nonviable tendons. Surgical

Fig. 7.2  Surgical debridement with Watson Dermatome on burn wound. This figure demonstrates a surgical debridement procedure performed on a burn wound using a Watson Dermatome. The image showcases the precise removal of necrotic tissue from the burn wound during the intraoperative stage. The use of the Watson Dermatome allows for controlled and effective debridement, ensuring a clean and prepared wound bed for further treatment

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debridement is indicated for a variety of conditions, including osteomyelitis, infectious arthritis, ascending cellulitis, extensive necrotic wounds, wounds with extensive undermining, foreign bodies, necrotic tissue near vital organs/ structures, and sepsis [27]. Surgical debridement techniques vary widely depending on the type of wound and the type of nonviable tissue to be removed. During the procedure, the physician performs a tissue biopsy to better establish the presence and type of infection. This is followed by appropriate antimicrobial therapy. However, surgical debridement has some disadvantages, including physical and emotional stress for the patient, high cost, and the risk of infection associated with any surgical procedure. It is important to note that surgical debridement should not be performed on patients who are unlikely to survive such a stressful procedure or patients with palliative care plans. The use of surgical debridement should also be approached with caution when dealing with patients who are thrombocytopenic or those on anticoagulants. It is important to evaluate the patient’s overall health status and comorbidities to determine whether surgical debridement is appropriate.

7.7.1 Hydrosurgery Hydrosurgery, also known as waterjet debridement, is a surgical tool used to remove nonviable tissue, bacteria, and contaminants from wounds. It is a precise and effective method of wound debridement that uses a high-pressure stream of sterile saline to remove unwanted tissue while minimizing damage to healthy tissue. This system is especially useful for extensive wounds, as it can quickly and thoroughly remove debris and necrotic tissue from a large wound bed [20]. The hydrosurgery system consists of a specialized handpiece that produces a high-velocity stream of saline. The handpiece is equipped with a tiny jet nozzle that directs the stream of saline onto the wound bed. As the saline stream hits the wound bed, it dislodges and removes nonviable


Fig. 7.3  Hydrosurgical debridement. This figure illustrates the application of hydrosurgery for debridement using a power-assisted system. This machine utilizes a high-pressure fluid stream to precisely and selectively remove necrotic tissue, debris, and contaminants from the wound bed. The image captures the moment of debridement, showing the controlled and thorough removal of unhealthy tissue, while preserving the surrounding healthy tissue. Hydrosurgery offers a minimally invasive and effective method for debridement, promoting wound healing and preparation for further interventions

tissue and contaminants, leaving behind a clean, healthy wound bed. The handpiece also has an evacuation collector tube that collects the saline and debris, which is then deposited into a waste container (Fig. 7.3). One of the advantages of hydrosurgery is that it preserves healthy tissue while removing only the nonviable tissue. This tissue-preserving technique can reduce the time it takes for a wound to heal and can also reduce the overall cost of treatment. In addition, because hydrosurgery is a minimally invasive procedure, it can be used to debride wounds in sensitive areas of the body that would be difficult or impossible to treat with other methods [21]. However, hydrosurgery is not appropriate for all wounds. It should not be used on deep tunneling wounds or on patients taking anticoagulants, as the high-pressure saline stream can cause bleeding in these cases. It is also important to note that hydrosurgery produces an aerosolized mist that can contain bacteria and other contaminants. As a result, both the patient and clinician must wear appropriate barrier devices during the procedure to avoid inhaling any harmful particles.


T. Pasquale and M. Maruccia

7.8 Other Types of Debridement

bed, effectively vaporizing and ablating the necrotic tissue. The laser energy can be adjusted In addition to the main methods of debridement to target specific types of necrotic tissue, providmentioned earlier, there are other approaches that ing a controlled and precise debridement can be explored in the management of ulcers. process. One of the key advantages of laser debrideThese alternative methods offer additional ment is its ability to promote hemostasis during options for healthcare professionals to consider the procedure. The laser energy seals blood veswhen tailoring the debridement approach to indisels as it removes the necrotic tissue, reducing vidual patients. bleeding and improving visibility for the healthcare professional. Laser debridement also has the potential to stimulate wound healing by promot7.8.1 Ultrasound Debridement ing collagen synthesis and cellular activity. It is important to note that laser debridement Surgical debridement with ultrasound is a relamay require specialized equipment and expertise, tively newer technique that utilizes the power of and it is not widely available in all healthcare setultrasonic energy to aid in the removal of necrotic tissue. This method involves the use of low-­ tings. Additionally, certain precautions must be frequency ultrasonic waves delivered through a taken, such as proper eye protection for both the specialized handpiece or probe. The ultrasonic patient and healthcare professional, to ensure energy disrupts and breaks down the necrotic tis- safe implementation of the procedure. In conclusion, beyond the main methods of sue, allowing for easier removal. debridement, debridement with ultrasound and One of the advantages of surgical debridement laser debridement present additional options for with ultrasound is its precision and selective tarhealthcare professionals in the management of geting. The ultrasonic energy specifically targets and breaks down the necrotic tissue, minimizing ulcers. These techniques offer benefits such as damage to healthy tissue. This technique can be precision, selectivity, improved visibility, reduced particularly useful in areas with delicate or hard-­ bleeding, and potential wound healing stimulato-­reach ulcers, such as around bony prominences tion. However, their utilization requires careful consideration of factors such as patient suitabilor in deep wounds. Moreover, surgical debridement with ultra- ity, available resources, and the expertise of the sound is generally well-tolerated by patients and healthcare team. Exploring these alternative may result in less pain compared to traditional approaches expands the options for debridement sharp debridement methods. It can also be per- and contributes to comprehensive ulcer manageformed at the bedside, making it a convenient ment strategies. option for patients who may not be suitable for more invasive procedures [28].

7.8.2 Laser Debridement

7.9 Factors to Consider in Choosing the Debridement Method

Laser debridement is another innovative approach that utilizes the energy of laser light to remove necrotic tissue from ulcers. In this technique, a focused laser beam is directed onto the wound

Choosing the appropriate method of debridement for a specific ulcer is a critical decision in wound management. Several key factors influence the selection process, ensuring the most effective and

7  Ulcer Debridement

tailored approach to promote healing. By considering the size, depth, type of necrotic tissue, presence of infection, ulcer location, and patient’s overall condition, healthcare professionals can make informed decisions to optimize outcomes. The size and depth of the ulcer play a crucial role in determining the appropriate debridement method. Larger and deeper ulcers often require more aggressive debridement techniques to remove extensive necrotic tissue and facilitate the healing process. In contrast, smaller ulcers with minimal necrotic tissue may benefit from less invasive debridement methods that focus on selective removal, preserving healthy tissue. The type of necrotic tissue present in the wound bed is another essential factor. Different debridement methods target specific types of necrotic tissue, such as slough or eschar. For instance, autolytic debridement using moisture-­ retentive dressings is effective in promoting the body’s natural enzymatic action to liquefy and remove soft necrotic tissue. However, enzymatic debridement employing topical enzymes may be more suitable for thick eschar or fibrin deposits that require enzymatic breakdown. The presence of infection in the ulcer influences the choice of debridement method. Infected ulcers often necessitate more aggressive debridement approaches to eliminate bacterial burden and facilitate effective wound healing. Sharp debridement or surgical debridement may be considered in these cases to achieve thorough removal of infected tissue and reduce the risk of further complications. The location of the ulcer is a critical consideration when selecting the debridement method. Some areas of the body, such as the face or near vital structures, require more cautious approaches to ensure minimal damage and optimal outcomes.


In these situations, less invasive methods such as autolytic or enzymatic debridement may be preferred. However, in accessible areas, mechanical debridement or sharp debridement can be employed to achieve precise and thorough tissue removal. The patient’s overall condition and comorbidities must be taken into account when choosing the debridement method. Factors such as the patient’s pain tolerance, mobility, vascular status, and ability to tolerate certain procedures play a role in determining the most appropriate approach. For instance, patients with compromised vascular supply may not be suitable candidates for surgical debridement due to the risk of poor wound healing and complications. In such cases, less invasive methods such as autolytic or enzymatic debridement may be more appropriate. The choice of debridement method for a specific ulcer is multifaceted and requires a comprehensive assessment of various factors. Understanding the size, depth, type of necrotic tissue, presence of infection, ulcer location, and the patient’s overall condition enables healthcare professionals to tailor the debridement approach to optimize wound healing. By considering these factors, clinicians can select the most suitable debridement method and promote successful wound bed preparation, setting the stage for effective ulcer management and improved patient outcomes. Table 7.1 provides a comprehensive indication and recommendation on dressings and various debridement methods used in wound management. Table 7.2 provides a comprehensive comparison of various debridement methods used in wound management.

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72 Table 7.1  Debridement methods’ indication and recommendation Debridement Types Autolytic Hydrogels (e.g., Nu-Gel®, Purilon®) Hydrocolloids (e.g., DuoDERM®, Comfeel®) Hydrofibers (e.g., AQUACEL®) Alginate (e.g., Algisite®)

Honey-based (e.g., Medihoney®) Enzymatic

Collagenase (e.g., Noruxol®, Bionect®)

Papain-urea (e.g., Accuzyme®) Trypsin (e.g., Granulex®) Bromelain (e.g., NexoBrid®)



Wet-to-dry dressings, hydrophobic dressing, scrubbing, wound irrigation, wound debridement pads Sharp surgical instruments, laser, hydrosurgery

Indications Dry necrotic wounds, superficial wounds, wounds with minimal exudate Necrotic wounds, pressure ulcers, leg ulcers, burns, wounds with granular tissue Cavity wounds, deep wounds, surgical wounds, infected wounds Wounds with moderate-to-heavy exudate, infected wounds, cavity wounds Infected wounds, wounds with minimal-to-moderate exudate, burns, surgical wounds Partial- to full-thickness wounds, wounds with necrotic tissue, and burns. The presence of yellow, fibrous, or thick slough indicates the need for collagenase. Chronic wounds with devitalized tissue, pressure ulcers, diabetic foot ulcers, and venous ulcers. Chronic wounds with slough, burns, and traumatic injuries. Partial- to full-thickness wounds, burns, and wounds with necrotic tissue or eschar. Wounds with moderate-to-heavy exudate

Not recommended Infected wounds, heavily exuding wounds Infected wounds, heavily exuding wounds

Necrotic or infected tissue, severe burns, wounds with necrotic tissue or eschar

Granulating wounds, newly formed tissue, painful wounds

Dry wounds Dry wounds, wounds with minimal exudate Dry wounds, allergies to honey Clean, granulating wounds, known hypersensitivity to collagenase Clean, granulating wounds Clean, granulating wounds Clean, granulating wounds Granulating wounds, newly formed tissue, painful wounds

Table 7.2  Debridement methods’ comparison Type Autolytic debridement

Enzymatic debridement

Biological debridement

Description Dressings, such as hydrogels, hydrocolloids, and alginate, are used to encourage the body’s natural enzymes and moisture to break down dead tissue. Collagenase-based dressings or ointments are applied to break down collagen in necrotic tissue. Use of live fly larvae to consume necrotic tissue

Advantages Non-invasive, painless, and can be used for a variety of wound types.

Disadvantages Can be slow and ineffective for larger wounds or those with heavy slough or eschar.

Selectively targets necrotic tissue, painless, and can be effective for larger wounds or those with heavy slough or eschar. Effective for heavily necrotic tissue, non-invasive

Can be costly, requires frequent dressing changes.

Unappealing to some patients and healthcare providers, requires careful management and monitoring, may be contraindicated for certain patients or wounds


7  Ulcer Debridement Table 7.2 (contnued) Type Mechanical debridement

Surgical debridement

Description Wound irrigation or use of specialized tools, such as curettes or scalpels, to physically remove necrotic tissue. Sharp surgical instruments are used to remove necrotic tissue and debris from the wound.

Advantages Rapid and effective for larger wounds or those with heavy slough or eschar, can be combined with other types of debridement. Rapid and effective, can remove debris and foreign objects, can be combined with other types of debridement.

References 1. Guest JF, Ayoub N, McIlwraith T, et al. Health economic burden that different wound types impose on the UK’s National Health Service. Int Wound J. 2017;14(2):322–30. iwj.12603. 2. Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair Regen. 2003;11(Suppl 1):S1–28.­475x.11.s2.1.x. 3. Kirshen C, Woo K, Ayello EA, Sibbald RG.  Debridement: a vital component of wound bed preparation. Adv Skin Wound Care. 2006;19(9):506–17.; quiz 517-519. https://doi. org/10.1097/00129334-­200611000-­00011. 4. Kottner J, Cuddigan J, Carville K, et  al. Prevention and treatment of pressure ulcers/injuries: the protocol for the second update of the international clinical practice guideline 2019. J Tissue Viability. 2019:28. 5. Maruccia M, Onesti MG, Sorvillo V, et al. An alternative treatment strategy for complicated chronic wounds: negative pressure therapy over mesh skin graft. Biomed Res Int. 2017;2017:8395219. https:// 6. Atkin L.  Understanding methods of wound debridement. Br J Nurs. 2014;23(12):S10-12., S14-15. 7. Giudice G, Filoni A, Maggio G, et  al. Use of the stromal vascular fraction in intermediate-deep acute burns: a case with its own control. J Burn Care Res. 2018;39(5):846–9. irx017. 8. Wolcott RD, Kennedy JP, Dowd SE. Regular debridement is the main tool for maintaining a healthy wound bed in most chronic wounds. J Wound Care. 2009;18(2):54–6. jowc.2009.18.2.38743. 9. Atkin L, Rippon M.  Autolysis: mechanisms of action in the removal of devitalised tissue. Br J Nurs.

Disadvantages Can be painful and invasive, may cause bleeding or damage to healthy tissue, requires specialized training and equipment. Invasive, requires anesthesia, may cause bleeding or damage to healthy tissue, can be costly, and may require hospitalization.

2016;25(20 Suppl):S40–7. bjon.2016.25.20.S40. 10. Nuutila K, Eriksson E.  Moist wound healing with commonly available dressings. Adv Wound Care (New Rochelle). 2021;10(12):685–98. https://doi. org/10.1089/wound.2020.1232. 11. Ramundo J, Gray M.  Enzymatic wound debridement. J Wound Ostomy Continence Nurs. 2008;35(3):273–80. WON.0000319125.21854.78. 12. McCallon SK, Weir D, Lantis JC. Optimizing wound bed preparation with collagenase enzymatic debridement. J Am Coll Clin Wound Spec. 2014;6(1-2):14– 23. 13. Cigna E, Maruccia M, Sorvillo V, Parisi P, Palumbo F, Onesti MG. The use of negative pressure therapy and hyaluronic acid for the management of post-traumatic lower limb injury. Int Wound J. 2013;10(5):534–8.­481X.2012.01011.x. 14. Sherman RA, Hall MJ, Thomas S.  Medicinal maggots: an ancient remedy for some contemporary afflictions. Annu Rev Entomol. 2000;45:55–81. https://doi. org/10.1146/annurev.ento.45.1.55. 15. Qing C.  The molecular biology in wound healing & non-healing wound. Chin J Traumatol. 2017;20(4):189–93. cjtee.2017.06.001. 16. Kammerlander G, Andriessen A, Asmussen P, Brunner U, Eberlein T. Role of the wet-to-dry phase of cleansing in preparing the chronic wound bed for dressing application. J Wound Care. 2005;14(8):349– 52. 17. Onesti MG, Fioramonti P, Carella S, Maruccia M. The importance of periwound skin in the treatment of “difficult wound”. G Chir. 2011;32(1-2):83–8. 18. Choi JS, Lee JH, Kim SM, Kim YJ, Choi JY, Jun YJ.  Hydrogel-impregnated dressings for graft fixation: a case series. J Wound Care. 2015;24(7):326–8. 19. Norman G, Atkinson RA, Smith TA, et  al. Intracavity lavage and wound irrigation for prevention of surgical site infection. Cochrane Database

74 Syst Rev. 2017;10(10):CD012234. https://doi. org/10.1002/14651858.CD012234.pub2. 20. Onesti MG, Carella S, Maruccia M, Marchese C, Fino P, Scuderi N.  A successful combined treatment with dermal substitutes and products of regenerative medicine in a patient affected by extravasation injury from hypertonic solution. In Vivo. 2012;26(1):139–42. 21. Morisaki A.  A combination of hydrodebridement with pulsed lavage and negative pressure wound therapies may enhance outcomes. J Card Surg. 2022;37(9):2745–6. jocs.16700. 22. Dijoux C, Ribal E, Téot L. Use of a moderate-­pressure irrigation system to effect debridement in the home setting. J Wound Care. 2008;17(3):134–6., 138. 23. Bath MF, Suresh R, Davies J, Machesney MR. Does pulsed lavage reduce the risk of surgical site infection? A systematic review and meta-analysis. J Hosp

T. Pasquale and M. Maruccia Infect. 2021;118:32–9. jhin.2021.08.021. 24. Vowden KR, Vowden P. Wound debridement, Part 2: Sharp techniques. J Wound Care. 1999;8(6):291–4. 25. Bluestein D, Javaheri A. Pressure ulcers: prevention, evaluation, and management. Am Fam Physician. 2008;78(10):1186–94. 26. Téot L.  Surgical debridement of wounds. Soins. 2011;752:36–7. 27. Prodromidis AD, Charalambous CP. The 6-hour rule for surgical debridement of open tibial fractures: a systematic review and meta-analysis of infection and nonunion rates. J Orthop Trauma. 2016;30(7):397–402. 28. Saggini R, Saggini A, Spagnoli AM, et  al. Extracorporeal shock wave therapy: an emerging treatment modality for retracting scars of the hands. Ultrasound Med Biol. 2016;42(1):185–95. https://doi. org/10.1016/j.ultrasmedbio.2015.07.028.


Advanced Moist Wound Dressing: Classification by Function Alessandro Greco, Mastronicola Diego, Natascia Mennini, and Magnoni Cristina

The panorama of dressings for skin ulcers represents a continuum of products ranging from traditional gauze to bioengineered tissues. This therapeutic baggage is enriched day after day with new aids that often find it difficult to be categorized according to the traditional product classification used so far. In fact, there are dressings consisting of combinations of several individual components, each of which is characterized by its own distinctive quality, but which combined together can acquire a completely different one. Moreover, dressings belonging to different product categories can actually perform the same function once in contact with the wound bed. Many new products are incorrectly inserted into pre-existing categories dedicated to other products, due to the fact that they contain a particular ingredient (as in the case of hydrocolloids), leaving numerous questions open on appropriateness of use. Currently, the effectiveness of appropriate wound dressings on tissue repair process is A. Greco (*) · M. Diego Outpatient Wound Care Centre, Local Health Care System, Frosinone, Italy N. Mennini Department of Chemistry, University of Florence, Florence, Italy e-mail: [email protected] M. Cristina Unit of Dermatologic Surgery, University of Modena and Reggio Emilia, Modena, Italy

widely accepted. It is well established that no wound will heal if the factors that inhibit tissue repair in each stage are not addressed properly. The optimal choice of an advanced dressing is based on two fundamental aspects: a precise understanding of the mechanisms that underlie the phases of the wound healing and a deep knowledge of the properties of the different dressing present on the market today. To do this, clinicians need to be familiar with the physical and chemical properties of dressing components, the differences between products, and their mechanism of action and synergy with dressing’s scaffold. Since 1960, a multitude of products have been designed to ideally create a perfect wound environment. In 1991, Bolton [1] first introduced the important role played by wound dressings in meeting clinical and biological needs, in order to achieve optimal results in wound management. A precise wound assessment and an appropriate selection of wound care products are of utmost importance. Given the development of new advanced dressings and systems, in 2006 Van Rijswik [2] provided a review of wound dressings according to their function instead of their material composition. In 2011, Cutting [3] urged for a revision of wound dressing classification following clinical objectives, again, based on a dressing’s function. In 2014, T.  Phillips [4] stressed the significance of wound characteristics as a guide in selecting the proper dressing, in order to achieve

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,


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a faster wound healing. She suggested that wound dressing selection should be guided by product characteristics according to wound assessment: superficial wound, wound with eschar, and exudating wounds. To date, the literature classifies dressing based on their mechanisms of action or on the concept of TIME. However, these classifications are only partially applicable, due to the increasing number of dressings, which are highly innovative but do not always fit into existing categories [5–8]. Clearly, there is a need to classify dressings based on their function, but no attempts have been successfully done till now in implementing this new classification. This article would like to present a classification of wound dressings based on their function.

8.1 Classification by Function “Status-Based” Wound healing is an extremely complex process involving several biological and molecular activities. The main physiological events in the achievement of tissue restoration include coagulation, inflammation, cellular proliferation and migration, re-epithelialization, and remodeling. Wound bed preparation is based on a precise sequence of tissue repair processes that include

tissue homeostasis, infection control, exudate balance, and progress to epithelialization of wound margins [9]. It is important for the healthcare professional to recognize the predominant clinical obstruction/sign, to identify the clinical condition of the wound at that time. The predominant (prevalent) sign • It is defined as the most evident sign upon clinical assessment of the wound and the surrounding skin. • The clinical sign (signs) determines the choice of the most appropriate dressing at that specific moment. It is possible to identify the main categories of dressing by their functions and divide them according to their main mode of action, by carefully examining the sequences of the tissue repair process (status). This paper aimed to offer the HCP a guide to each type of dressing’s primary function and, therefore, its main therapeutic indication. Many technologically advanced dressings have secondary, ancillary, or independent functions, in addition to the main function. The role of these accessory functions can be decisive in specific clinical conditions. The division by function consists of four main categories: [10] (Fig. 8.1)

Fig. 8.1  Four main categories of dressings classified according to function

8  Advanced Moist Wound Dressing: Classification by Function


Fig. 8.2  Category and subcategories of dressings that promote autolysis and debridement

1. Dressings that promote autolysis and debridement. 2. Dressings that promote granulation tissue. 3. Antimicrobial dressings. 4. Dressings that promote epithelialization and protect the surrounding skin.

sheets that are impermeable to fluids or honey dressing. Autolytic debridement, one of the most commonly used methods, is based on the ability of some dressings to stimulate the degradation capacity of fibrin by endogenous enzymes activated in a moist environment [13]. The dressings capable of ensuring this pri8.1.1 Dressings that Promote mary function are fluid and support hydrogels, Autolysis and Debridement hydrocolloid paste and plaque, saturated polyacrylates, dextranomer, saline gauze, and hyperThe presence of slough, black necrotic tissue, or tonic hydrogels. devitalized tissue, in general, represents an obstaHydrogels are cross-linked polymers consistcle to the healing process, in addition to being a ing mainly of water and available in the form of soil for bacteria [11, 12]. plaques, amorphous gel, or impregnated gauze. Some of the dressings can remove the necrotic Thanks to their high water content, they are ideal tissue by autolysis debriding. Analysis of these on dry lesions on which they perform their main dressings allows for their classification into two function, which is to hyperhydrate necrotic tisgroups, which represent their different mode of sues and favorite endogenous lysis. An accessory action: physical-chemical and biochemical function commonly performed by hydrogels is to (Fig. 8.2). soothe particularly painful ulcers [14, 15]. The first group consists of all the products of All products that have a similar functional which the primary function is to enhance the ability but are composed of enzymes and have body’s own phagocytosis process, so as to an enzymatic mode of action (collagenase, cataremove, reduce, or soften the devitalized tissue lase, papain, non-specific proteases, bromelainthrough the help of moistening, watering, or by based, etc.) belong to the second group. They osmotic action. They range from propylene-­ act by penetrating and digesting non-viable tisglycol/glycerin or water-based polymers (amor- sue and fibrin without damaging healthy viable phous or sheet hydrogels) to occlusive pasts or tissue [16].

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Enzymatic debridement involves the use of chemical agents capable of dissolving collagen or devitalized tissues present on the wound bed. Collagenase derives from a bacterium, Clostridium histolyticum, and is used in the form of ointment on ulcers with low exudation, with eschar or adhering fibrin [17, 18]. Debridement can also be favored by the mechanical function of some products that exploit the desloughing capacity of polyester monofilaments rubbed on the lesion [19]. Other products perform mechanical debridement through the property of special anchoring and absorbent polyacrylate fibers with silver that also provide a vicarious antiseptic function [20, 21].

8.1.2 Dressings that Promote Granulation Tissue At the start of the inflammatory process, fibroblasts and vascular endothelial cells commence proliferating. In particular, when healing takes place by secondary intention, the bigger the extent of tissue damage and the intensity of the inflammatory response, the larger the amount of

granulation tissue that will be necessary to cover the substance loss [22]. The repair process in chronic wounds is altered. The most evident clinical markers that express such alterations are excessive or insufficient production of exudate with variable viscosity and/or the presence of an unhealthy-looking (dystrophic) granulation tissue [23]. The primary function of dressings in this group consists of promoting, protecting, or stimulating these granulation processes consisting of macrophages fibroblasts, and vessels proliferating and invading wound space to obtain a typically pink o red wound bed filled to reach the level of surrounding intact skin. There are two major modes of action through, which these dressings carry out their functions: by homeostasis of fluids and by bio-interaction (Fig. 8.3). Homeostasis of Fluids In wounds with scarce amounts of moisture, exudate balance can be obtained using occlusive dressings (hydrocolloids). Occlusive dressings act by increasing the level of moisture in the microenvironment and stimulating angiogenesis by reducing the pO2 [24, 25].

Fig. 8.3  Category and subcategories of dressings that promote granulation

8  Advanced Moist Wound Dressing: Classification by Function

Hydrocolloids are cross-linked polymers in a colloidal state made up of water and various gelling substances dispersed inside them such as gelatin, pectin, or carboxymethylcellulose. The structure of these dressings is then completed with the presence of elastomers and adhesives applied on support (generally polyurethane film). They are commercially available, as well as on support, also in the form of pastes and powders. These dressings are impermeable to water and bacteria but allow the exchange of water vapor. In contact with exudate, they absorb a minimum quantity by changing their gel state. They are characterized not only by their ability to stimulate granulation, which represents their primary function, but also by their ability to stimulate autolytic debridement, which we consider as a secondary function [26]. For a long time, they represented the most used advanced dressings. In exuding wounds that have no clinical sign of infection or critical colonization, the homeostasis of the fluids is determined by the ability of some dressings to remove the excess exudate. These dressings act by simply absorbing (alginates or polyurethane foams) and/or by retaining the exudates (cellulose fibers, superabsorbent polymers, etc.), thus balancing the local moisture on the wound surface (passive absorbency) [27]. Passive absorbency is defined as the intrinsic capacity of some dressings to absorb and/or retain the fluids without the use of external energy [10]. In the case of lesions with abundant exudate, but no clinical signs of infection, dressings can absorb and remove excess liquids from the lesion. Based on the type of absorption, we distinguish dressings that act by passive or active absorption. The dressings that are characterized by passive absorption of exudate exploit the intrinsic ability to absorb and/or retain fluids without the use of external energy, and we will distinguish them into simple, retaining exudate, or hemostatic [10]. Examples of “simple” dressings favoring fluid granulation by homeostasis through passive absorption include polyurethane foams, alginates, and polyester with hydrated cellulose. Polyurethane foams, like hydrocolloids, are also


used a lot in particular on pressure ulcers. The foam dressings are composed of polyurethane coated with a semi-exclusive external layer and guarantee adequate absorption for medium–high exudates while allowing an exchange of gas between the wound bed and the external environment. They are transpiring to water vapor but are impermeable to water and bacteria while maintaining the right degree of humidity and optimal thermal insulation (35–37 °C) on the wound bed [28]. Thanks to their thickness and non-rigid structure, they are extremely comfortable on particularly difficult-to-treat wound sites such as bony prominences. They are divided into adhesive or non-adhesive, requiring in this second case adherent secondary dressings. In recent years, polyurethane foams have evolved into technically and structurally complex products that require further differentiation into simple with open and/or isomorphic single- or double-layer cells, complex with atraumatic, multilayer, and mixed cell interface or edges, and interconnected and finally composite, or multilayer combined with other technologies such as cellulose, carboxymethylcellulose (CMC), hydrocolloids, or superabsorbent polymers (SAP). In the group of dressings stimulating granulation for homeostasis of fluids through passive and “retention of exudate” absorption, we include cellulose fibers, superabsorbent polymers (SAPs), CMC, and polyurethane foam combination dressings, cellulose, SAP, and foam combination dressings, polyurethane and finally dextranomer. Dressings made of chemically modified cellulose fibers include hydrofibers made up of 100% CMC and similar, made up of 80% ethyl sulfonated cellulose fibers and 20% cellulose. Hydrofibers (100% sodium CMC) represent highly absorbent dressings composed of sodium carboxymethylcellulose. When they absorb the exudate, its fiber gel allowing the maintenance of a humid environment on the wound bed favors autolytic debridement and granulation [29]. The absorption capacity is three times greater than for alginates, particularly useful in highly exuded lesions and partial thickness burns. Their


soft and conformable structure allows their use on cavitary and underlined lesions. The peculiar feature of these dressings is to ensure vertical absorption by preventing lateral propagation of exudates and maceration of the peri-wound skin [30, 31]. Dressings based on polyvinyl alcohol (PVA) fibers capable of absorbing exudate through a gelation mechanism have also recently been introduced on the market. PVA is a linear synthetic polymer produced by partial or complete hydrolysis of polyvinyl acetate. PVA is used as a biomaterial due to its biocompatibility and nontoxic and non-carcinogenic properties [32]. The dressings based on polyacrylates, or superabsorbent polymers, are characterized by a high hydrocapillary absorption capacity and a non-adherent cross-linked interface. Also, in this case, a high absorption and retention capacity of the exudate is guaranteed with the absence of leakage. This ability resides in the structure that constitutes the central pad (hydrocapillary superabsorbent pad) composed of carboxymethylcellulose (CMC) and superabsorbent particles (SAPs) consisting of polymers of sodium polyacrylate). Gelling foams, on the other hand, consist of a combination of hydrofiber, hydrocolloid, and polyurethane foam. They are characterized by a low profile of the structure and a high capacity for absorption and retention in a structure that can be adhesive or not according to the needs. Hydrophobia with different textures in contact with the wound bed guarantees these properties. Some of the dressings also have a combined homeostatic property (calcium alginates and collagen) [33]. “Hemostatic”: Two are the technologies that make up this subgroup, namely alginates and collagen dressings. Alginates are a family of dressings composed of polysaccharides derived from various species of brown seaweed or Phaeophyceae, characterized by a wide variety of chemical composition, molecular weight, and functional properties. Chemically, they are made up of non-branched copolymers of β-D-­ mannuronic acid and its α-L-guluronic acid epimer. Thanks to their ability to absorb fluids up to 20 times their weight, they are considered highly

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absorbent dressings indicated for abundantly exuded ulcers. The calcium ions released also have a hemostatic effect thanks to the promotion of the coagulation cascade [34]. Other dressings transport the exudate away from the wound by suction with negative pressure (active absorption). Active absorption refers to the ability of some dressings to absorb fluids thanks to a process activated by an external energy source. The negative pressure therapy dressing positively affects the granulation tissue by stimulating cellular mitosis [35–37]. Thanks to mechanical forces inducing physical macro and biological micro-responses, this therapy is able to play a major role in promoting tissue reconstruction. Bio-Induction In the presence of devitalized tissue without clinical signs of infection or critical colonization, the stimulation of granulation tissue is induced by dressings that interact with the wound bed and release bioactive components (Fig.  8.3). These products act as reservoirs for growth factors (platelet gel) or as matrix scaffolds allowing the formation of new tissue (collagen or hyaluronic acid) by attracting fibroblasts and macrophages into the wound bed. In fact, the granulation process can be promoted and stimulated by biomaterials that play an important role in the healing process. These dressings are known for their biocompatibility, biodegradability, and nontoxic nature and are generally derived from natural tissues or artificial sources such as collagen [38, 39], hyaluronic acid [40–42], and chitosan [43]. Polymers of these materials are used alone or in combination depending on the nature and type of wound. Biological dressings are sometimes incorporated with growth factors and antimicrobials to enhance the wound healing process. Collagen initiates fibroblast formation and accelerates endothelial migration upon contact with wound tissue [44]. Hyaluronic acid (HA) is a glycosaminoglycan component of the extracellular matrix (ECM) with unique biological and physicochemical characteristics. Similar to collagen, HA is also

8  Advanced Moist Wound Dressing: Classification by Function

biocompatible, biodegradable, and naturally immunogenic [45]. Chitosan promotes granulation tissue formation during the proliferative phase of wound healing [46, 47]. Dressings with technology lipid-colloid (TLC) is a jellified matrix of CMC and fatty particles, and octasulfate salt of potassium (TLC-­ NOSF) shows special activity in stimulating fibroblast proliferation and reducing matrix metalloproteinases. The activity of TLC on fibroblast proliferation was determined by the presence or absence of increased incorporation of tritiated thymidine into the DNA of replicating normal human dermal fibroblasts [48]. The effectiveness of TLC-NOSF in reducing MMP activity has been demonstrated in  vitro [49]. The polyacrylate fiber chassis of these dressings has absorbent, retention, and partial debridement capabilities.

8.1.3 Antimicrobial Dressings Infection is one of the main factors that compromise healing in the wound, especially in chronic ulcers [50]. The correct use of dressings that contain antimicrobial agents can be helpful in controlling critical colonization and local infections and in promoting healing [51]. Antimicrobial dressings include products that incorporate an antiseptic agent, which is a biocide used to kill the microorganisms present in the wound or on intact skin or inhibit their growth. Recent advances in technology have led to the development of a large number of antiseptic products that are less harmful to healthy tissue while being extremely effective in pathogens colonization. These antiseptics include silver, zinc oxide, copper oxide, titanium oxide, and iodine. Dressings that incorporate such antiseptics can be successfully used to avoid microbial contamination [52–55]. Zinc oxide nanoparticles (ZnO-NPs) exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size


leads to enhanced particle surface reactivity. Particular emphasis was given to bactericidal and bacteriostatic mechanisms with a focus on the generation of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), ·OH (hydroxyl radicals), and ·O2−2(peroxide anion) [56]. Any capable of killing bacteria is said to be a bactericide. Bactericides can be of physical and chemical type [57]. Most of the antimicrobial dressings contain topical chemical agents (chemical bactericide): metals such as silver and copper or antiseptic surfactants (PHMB). All these substances perform their antimicrobial (antibacterial, antifungal, and antiviral) function by inducing the denaturation of the proteins of the bacterium or the rupture of the cell wall by mechanical stress, thus causing the death of the microorganism. However, some antimicrobial dressings have only bacteriostatic activity. Bacteriostatic is any physical or chemical agent capable of partially or completely inhibiting the reproduction of bacteria (keep them in the stationary phase of growth) [58, 59]. Some examples of chemical agents of natural polymers with bacteriostatic action are dialkyl carbamoyl chloride (DACC) [60] and chitosan [46, 61]. Silver has been shown to be very effective in reducing biofilms in and on medical devices [62]. Studies on the effects of silver on biofilms have been carried out highlighting positive anti-­biofilm capabilities of ionic silver specifically when used in combination with specific platforms, actives, and chassis [63]. Antimicrobial dressings can be divided into simple and composite dressings [10]. Simple antimicrobial dressings exert antimicrobial activity, whereas composite dressings, besides exerting antimicrobial action, have other functions, including maintaining moisture balance, debridement, or bioactivity (Fig.  8.4). For example, novel antimicrobial wound dressings impregnated with copper oxide micro-particles seem to play a key role in angiogenesis and the expression and stabilization of extracellular skin proteins and also exhibit biocidal properties [64, 65].


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Fig. 8.4  Category and subcategories of antimicrobial dressings with bactericidal and bacteriostatic actions

The accessory function of composite antimicrobial dressings is chosen mainly based on qualitative and quantitative characteristics of the exudate present. The moisture balance of infected exudate refers to the accessory capability of some dressings to act on the quantitative (volume) and qualitative (viscosity) restoration of exudate [10]. There are antimicrobial dressings, which have an accessory function of deslough through the hyperosmotic action of the main constitutive matrix, which favors the debridement of the wound. (manuka honey) [66–68].

8.1.4 Re-Epithelializing Eudermal Dressings Re-epithelialization, which is the proliferation by advancement of the epithelial margins, is a very delicate moment in the end process of the healing of chronic wounds. In this particular stage, the priority is not disrupting the epithelialized wound. Many factors can influence or interfere with this process: maceration, xerosis, hyperkeratosis, micro-trauma, dermatitis, infection, etc. The main functional objectives of dressings belonging to this category are to ensure the right

level of moisture in a protected microenvironment, so that proliferation and migration of keratinocytes may be facilitated, to maintain or re-establish the physiological parameters of the surrounding skin. We defined dressings in this category as eudermal dressings. Eudermic is a definition that indicates that substance or preparation that is able to improve the physiological state of the skin. Eudermal dressings are characterized by the ability to improve the physiological condition of the skin [10]. Two main subgroups belong to this category: protective dressings and maceration prevention/lenitive dressings (Fig.  8.5). In the first group, we can place atraumatic mesh silicone and lipo-colloidal dressings and moistureretaining dressings (e.g., polyurethane film and thin foams, thin hydrocolloids, and patches). In the latter, we include dressings with lenitive effect (zinc oxide bandages and liquid acrylate films) or prevent maceration (modified cellulose fibers dressing able to absorb and retain exudate) • Protective dressings are capable of maintaining an adequate moisture level in a protected

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Fig. 8.5  Category and subcategories of dressings that promote epithelialization and protect surrounding skin

wound microenvironment where proliferation and migration of keratinocytes are promoted. We further distinguish them into atraumatic dressings and dressings favoring the moist environment. Atraumatic products include simple silicone mesh, hydrophobic polyester mesh, acetates, Vaseline and petrolatum gauze, and lipo-colloidal gauze. Protective agents favoring a moist environment include thin hydrocolloid plates, hydrogel plates, thin polyurethane foams, and polyurethane films. The latter are thin transparent polyurethane films permeable to gases and water vapor but impermeable to fluids and bacteria. Their main function is to maintain an optimal moist environment in superficial and granule-like, poorly exuding lesions that are close to re-­ epithelialization [69]. • An ancillary function of them is to prevent maceration when applied as a protectant on perilesional skin or sealant when combined with NPWT. • Soothing or preventing maceration dressings can maintain or restore physiological conditions on perilesional skin. These include polyurethane foams, acrylate liquid films, modified cellulose fibers, zinc oxide or zinc/ Ichthyol bandages or hydrocolloids, and alginate gels or soothing gauze with active ingredients.

8.2 Symptom-Based Dressings The symptom is a feeling reported by the patient that can cause an alteration of the normal felt sense of oneself and of one’s body in relation to a pathological condition. Symptoms such as pain and odor accompany the inflammatory or infective state of a lesion [70]. In some specific cases, the symptom intrusion can prevail over the clinical state and become the main criteria for dressing choice, for example, with palliative dressings for a fungating neoplastic wound (malodor) or the choice of dressings for Martorell’s ulcers (pain). This type of clinical decision is made after an appropriate assessment of the symptom and the patient’s priorities to allow for a more acceptable quality of life. However, also in these cases it is important not to overlook the local treatment based on the condition (status) of the wound, which will in perspective allow for the clinical improvement of the wound. We can distinguish two groups of dressings based on symptoms (Symptom-based dressing): dressings with analgesic and/or anti-­inflammatory function (polyurethane foams with non-steroidal anti-inflammatory drugs (NSAIDs) [71] and dressings for odor control (activated charcoal)

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Fig. 8.6  Category and subcategories of dressings that control malodour and pain

[72]. The latter can be simple or have combined functions, such as additional features for the control of exudate and/or bacterial load (activated charcoal dressing impregnated with silver) [73] (Fig. 8.6).

8.3 Conclusions The constant flow of new products and new technologies creates more and more disorientations for clinician in choosing the most suitable device for a given wound. The common classification of dressings based on their chemical composition is of little utility in clinical practice where instead a functional clinical classification of dressings is much more useful and usable. The aim of our work is to simplify this choice in such a way as to provide clinicians with an immediate and simplified tool for choosing the dressing not only based on this composition but also on its function. Dressing selection demands the healthcare professionals’ ability to “read” the wound and the

capacity to respond to the clinical predominant sign through a correct choice of modern wound dressing. The aim of classification by function is to provide the clinician with a tool that will allow him/ her to identify in a simple manner the appropriateness of the specific dressing in correspondence with the clinical condition and symptoms of a lesion (Fig. 8.7). It is the hope of the author that the continuous use and reference to this classification, especially in its primary indication, will provide the clinician with a tool that is simple to use. The application of an approach that clearly prioritizes the prevalent sign of the wound and accordingly indicates the choice of dressings will in time validate this tool. In addition, since classification by function is not based on the dressing product category, this means that the inclusion of new products with innovative technologies will be much easier in the future. The products will in any event have to be based on the tissue repair processes and will need to have a therapeutic effect.

8  Advanced Moist Wound Dressing: Classification by Function


Fig. 8.7  Overview of main categories and subcategories of dressings classified according to their functions

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11. Whiteside MCR, Moorehead RJ.  In: Leaper DJ, Harding KG, editors. Wounds: biology and management. Oxford University Press; 1998. p. 89. 12. Hofman D, et al. The role of larvae in delayed wound healing. Wound Healing: past, present and future (European Tissue Repair Society Focused Meeting, Venice, Italy) 1997, p.28. 13. Mulder G, Jones R, Cederholm-Williams S, Cherry G, Ryan T. Fibrin cuff lysis in chronic venous ulcers treated with a hydrocolloid dressing. Int J Dermatol. 1993;32(4):304–6. 14. Surowiecka A, Struzyna J, Winiarska A, Korzeniowski T.  Hydrogels in burn wound management—a review. Gels. 2022;8:122. gels8020122. 15. Holbert MD, Kimble RM, Chatfield M, Griffin BR. Effectiveness of a hydrogel dressing as an analgesic adjunct to first aid for the treatment of acute paediatric burn injuries: a prospective randomised controlled trial. BMJ Open. 2021;11:e039981. 16. De Decker I, De Graeve L, Hoeksema H, Monstrey S, Verbelen J, De Coninck P, Vanlerberghe E, Claes KEY.  Enzymatic debridement: past, present, and future. Acta Chir Belg. 2022;122(4):279–95. https:// Epub 2022 May 4. PMID: 35440290 17. Ramundo J, Gray M.  Collagenase for enzymatic debridement: a systematic review. J Wound Ostomy Continence Nurs. 2009;36(6 Suppl):S4–11. https:// 18. Patry J, Blanchette V.  Enzymatic debridement with collagenase in wounds and ulcers: a systematic review and meta-analysis. Int Wound J. 2017;14(6):1055–65. Epub 2017 Apr 25. PMID: 28440050; PMCID: PMC7950028

86 19. Meads C, Lovato E, Longworth L. The debrisoft(®) monofilament debridement pad for use in acute or chronic wounds: A NICE Medical Technology Guidance. Appl Health Econ Health Policy. 2015;13(6):583–94. s40258-015-0195-0. PMID: 26315567; PMCID: PMC4661219. 20. Dalac S, Sigal L, Addala A, Chahim M, et al. Clinical evaluation of a dressing with poly absorbent fibres and a silver matrix for managing chronic wounds at risk of infection: a non-comparative trial. J Wound Care. 2016;25(9):531–8. jowc.2016.25.9.531. 21. Percival SL, Suleman L. Slough and biofilm: removal of barriers to wound healing by desloughing. J Wound Care. 2015;24(11):498–510. jowc.2015.24.11.498. 22. Velnar T, Bailey T, Smrkolj V.  The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res. 2009;37(5):1528–42. 23. Gurtner GC, Werner S, Barrandon Y, Longaker MT.  Wound repair and regeneration. Nature. 2008;453(7193):314–21. 24. Knighton D, Silver IA, Hunt TK.  Regulation of wound-healing angiogenesis: effect of oxygen gradients and inspired oxygen concentration. Surgery. 1981;90:262–70. 25. Varghese MC, Balin AK, Carter DM, Caldwell D. Local environment of chronic wounds under synthetic dressings. Arch Dermatol. 1986;122:52–7. 26. Romagnolo SC, Benedetto AV. Wound dressings. In: Snow SN, Mikhail GR, editors. Mohs micrographic surgery. Madison: The University of Wisconsin Press; 2004. p. 219–31. 27. World Union of Wound Healing Societies (WUWHS). Principles of best practice: wound exudate and the role of dressings. A consensus document. London: MEP Ltd; 2007. 28. Derwin R, Patton D, Avsar P, Strapp H, Moore Z. The impact of topical agents and dressing on pH and temperature on wound healing: a systematic, narrative review. Int Wound J. 2022;19(6):1397–408. https:// Epub 2021 Dec 20. PMID: 34931445; PMCID: PMC9493238 29. Naik G, Harding KG.  Assessment of acceptability and ease of use of gelling fiber dressings in the management of heavily exuding wounds. Chronic Wound Care Manag Res. 2019;6:19–26. https://doi. org/10.2147/CWCMR.S162687. 30. Walker A, Brace J. A multipurpose dressing: role of a Hydrofiber foam dressing in managing wound exudate. J Wound Care. 2019;28(Sup9a):S4–S10. https:// PMID: 31536459 31. Mennini N, Greco A, Bellingeri A, De Vita F, Petrella F.  Quality of wound dressings: a first step in establishing shared criteria and objective procedures to evaluate their performance. J Wound Care. 2016;25(8):428–37. jowc.2016.25.8.428.

A. Greco et al. 32. Mogoşanu GD, Grumezescu AM.  Natural and synthetic polymers for wounds and burns dressing. Int J Pharm. 2014;463(2):127–36. https://doi. org/10.1016/j.ijpharm.2013.12.015. Epub 2013 Dec 22 33. Wang L, Hao F, Tian S, Dong H, Nie J, Ma G.  Targeting polysaccharides such as chitosan, cellulose, alginate and starch for designing hemostatic dressings. Carbohydr Polym. 2022;291:119574. Epub 2022 May 7. PMID: 35698393 34. Yu P, Zhong W.  Hemostatic materials in wound care. Burns. Trauma. 2021;9:tkab019. https://doi. org/10.1093/burnst/tkab019. PMID: 34541007; PMCID: PMC8445204 35. Morykwas MJ, Faler BJ, Pearce DJ, Argenta LC.  Effects of varying levels of subatmospheric pressure on the rate of granulation tissue formation in experimental wounds in swine. Ann Plast Surg. 2001;47:547–51. 36. Saxena V, Hwang CW, Huang S, Eichbaum Q, Ingber D, Orgill DP.  Vacuum-assisted closure: microdeformations of wounds and cell proliferation. Plast Reconstr Surg. 2004;114:1086–96. 37. Greene AK, Puder M, Roy R, Arsenault D, Kwei S, Moses MA, et al. Microdeformational wound therapy: effects on angiogenesis and matrix metalloproteinases in chronic wounds of 3 debilitated patients. Ann Plast Surg. 2006;56:418–22. 38. Ramshaw JAM, Werkmeister JA, Glatteur V.  Collagen based biomaterials. Biotechnol Rev. 1995;13:336–82. 39. Rao KP.  Recent developments of collagen-based materials for medical applications and drug delivery. J Biomater Sci Polym Ed. 1995;7:623–45. 40. Doillon CJ, Silver FH. Collagen-based wound dressing: effect of hyaluronic acid and fibronectin on wound healing. Biomaterials. 1986;7:3–8. 41. Graça MFP, Miguel SP, Cabral CSD, Correia IJ.  Hyaluronic acid—based wound dressings: a review. Carbohydr Polym. 2020;116364 https://doi. org/10.1016/j.carbpol.2020.116. 42. Cortes H, Caballero-Florán IH, Mendoza-Muñoz N, Córdova-Villanueva EN, Escutia-Guadarrama L, Figueroa-González G, Reyes-Hernández OD, González-Del Carmen M, Varela-Cardoso M, Magaña JJ, Florán B, Del Prado-Audelo ML, Leyva-­ Gómez G.  Hyaluronic acid in wound dressings. Cell Mol Biol (Noisy-le-Grand). 2020;66(4):191–8. PMID:32583795 43. Ishihara M, Nakanishi K, Ono K, Sato M, Kikuchi M, Saito Y, et al. Photo crosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. Biomaterials. 2002;23:833–40. 44. Mathew-Steiner SS, Roy S, Sen CK.  Collagen in wound healing. Bioengineering. 2021;8:63. https:// 45. Supp DM, Boyce ST.  Engineered skin substitutes: practices and potentials. Clin Dermatol. 2005;23:403–12.

8  Advanced Moist Wound Dressing: Classification by Function 46. Matica MA, Aachmann FL, Tøndervik A, Sletta H, Ostafe V.  Chitosan as a wound dressing starting material: antimicrobial properties and mode of action. Int J Mol Sci. 2019;20(23):5889. https:// PMID: 31771245; PMCID: PMC6928789 47. Ueno H, Mori T, Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv Drug Deliv Rev. 2001;52:105–15. 48. White R, Cowan T, Glover D.  Supporting evidence-­based practice: a clinical review of TLC healing matrix. 2nd ed. London: MA Healthcare Ltd; 2015. 49. Coulomb B, Couty L, Fournier B, et  al. Evaluation of the matrix impregnated with NOSF (Nano Oligo Saccharide Factor) in an in  vitro dermal reconstruction model. JPC. 2008;63(8):54–7. 50. White RJ. Wound colonization and infection: the role of topical antimicrobials. Br J Derm. 2003; 51. Vowden P, Cooper RA, European Wound Management Association (EWMA). Position document: management of wound infection. London: MEP Ltd; 2006. 52. Hebeish A, El-Rafie MH, EL-Sheikh MA, Seleem AA, El-Naggar ME.  Antimicrobial wound dressing and anti-inflammatory efficacy of silver nanoparticles. Int J Biol Macromol. 2014;65:509–15. https:// 53. Beele H, Meuleneire F, Nahuys M, Percival SL.  A prospective randomised open label study to evaluate the potential of a new silver alginate/carboxymethylcellulose antimicrobial wound dressing to promote wound healing. Int Wound J. 2010;7:262–70. https://­481X.2010.00669.x. 54. Adlhart C, Verran J, Azevedo NF, Olmez H, Keinänen-Toivola MM, Gouveia I, Melo LF, Crijns F.  Surface modifications for antimicrobial effects in the healthcare setting: a critical overview. J Hosp Infect. 2018;99:239–49. 55. Paduraru A, et  al. Antimicrobial wound dressings as potential materials for skin tissue regeneration. Materials. 1859;2019:12. ma12111859. 56. Oyarzun-Ampuero F, Vidal A, Concha M, Morales J, Orellana S, Moreno-Villoslada I.  Nanoparticles for the treatment of wounds. Curr Pharm Des. 2015;21(29):4329–41. 12821666150901104601. 57. Books GF, Caroll KC, Butel JS, Morse SA, Mietzner TA.  Medical microbiology. 26th ed. McGraw Hill Companies, Inc; 2013. 877 58. Rippon MG, Rogers AA, Ousey K.  Antimicrobial stewardship strategies in wound care: evidence to support the use of dialkylcarbamoyl chloride (DACC)- coated wound dressings. J Wound Care. 2021;30(4):284–96. jowc.2021.30.4.284. 59. McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action, and resistance. Clin Microbiol Rev. 1999;12(1):147–79.


CMR.12.1.147. Erratum in: Clin Microbiol Rev 2001 Jan;14(1):227. PMID: 9880479; PMCID: PMC88911 60. Totty JP, Bua N, Smith GE, Harwood AE, Carradice D, Wallace T, Chetter IC. Dialkylcarbamoyl chloride (DACC)-coated dressings in the management and prevention of wound infection: a systematic review. J Wound Care. 2017;26(3):107–14. https://doi. org/10.12968/jowc.2017.26.3.107. 61. Abd El-Hack ME, El-Saadony MT, Shafi ME, Zabermawi NM, Arif M, Batiha GE, Khafaga AF, Abd El-Hakim YM, Al-Sagheer AA.  Antimicrobial and antioxidant properties of chitosan and its derivatives and their applications: a review. Int J Biol Macromol. 2020;164:2726–44. ijbiomac.2020.08.153. Epub 2020 Aug 22 62. Gentry H, Cope S.  Using silver to reduce catheter-­ associated urinary tract infections. Nurs Stand. 2005;19:51–4. 63. Percival SL, McCarty SM. Silver and alginates: role in wound healing and biofilm control. Adv Wound Care (New Rochelle). 2015;4(7):407–14. https://doi. org/10.1089/wound.2014.0541. PMID: 26155383; PMCID: PMC4486446 64. Borkow G, Okon-Levy N, Gabbay J.  Copper oxide impregnated wound dressing: biocidal and safety studies. Wounds. 2010;22(12):301–10. 65. Melamed E, Kiambi P, Okoth D, Honigber I, Tamir E, Borkow G.  Healing of chronic wounds by copper oxide-impregnated wound dressings-case series. Medicina (Kaunas). 2021;57(3):296. https://doi. org/10.3390/medicina57030296. PMID: 33809898; PMCID: PMC8004176 66. Molan PC.  Debridement of wounds with honey. J Wound Technol. 2009;5:12–7. 67. White R.  Manuka honey in wound management: greater than the sum of its parts? J Wound Care. 2016;25(9):539–43. 68. Israili ZH.  Antimicrobial properties of honey. Am J Ther. 2014;21(4):304–23. mjt.0b013e318293b09b. 69. Fletcher J.  Using film dressings. Nurs Times. 2003;99(25):57. 70. Glynn C. The control of pain associated with chronic leg ulcers. In: The Oxford European wound healing course handbook. Oxford: Positif Press; 2002 pp 99–109. 71. Arapoglou V, Katsenis K, Syrigos KN, Dimakakos EP, Zakopoulou N, Gjødsbøl K, Glynn C, Schäfer E, Petersen B, Tsoutos D.  Analgesic efficacy of an ibuprofen-releasing foam dressing compared with local best practice for painful exuding wounds. J Wound Care. 2011;20(7):319–20., 322-5. https://doi. org/10.12968/jowc.2011.20.7.319. 72. Williams C.  Role of CarboFlex in the nursing management of wound odour. Br J Nurs. 2001;10(2):122– 5. 73. Hampton S. Actisorb Silver 220: a unique antibacterial dressing. Br J Community Nurs. 2001;6(8 Silver Suppl):17–9.


Dressing: Indications on Applications Gianmarco Turriziani, Federico Lo Torto, and Diego Ribuffo

9.1 Introduction Wound healing is an intricate and complex process with a multitude of interdependent components. While there are several classifications that have been proposed for wounds, wound healing in its most rudimentary form consists of four phases, which work in a cascade hemostasis, inflammation, proliferation, and remodeling [1]. Every wound undergoes these phases with variable lengths depending on the wound type and acuity. Faulty signals that lead to prolonged time in the inflammatory stage delay the wound healing process and are one reason for the development of chronic wounds. A wound is classified as chronic when wound healing is delayed by more than 3  weeks or when the wound fails to return to a functional state. Various pathological conditions can lead to the formation of an ulcer, such as vascular insufficiency (arterial and/or venous), infections, poorly controlled diabetes mellitus, and prolonged pressure injuries. There are extrinsic and intrinsic factors that can perpetuate the inflammatory phase and consequently the chronicity of an ulcer. Extrinsic factors include malnutrition, microbial infection, hypoxic conditions, smoking, cancer, radiation, G. Turriziani · F. Lo Torto · D. Ribuffo (*) Department of Plastic Reconstructive and Aesthetic Surgery, Sapienza Università di Roma, Rome, Italy e-mail: [email protected]

and medications; among the intrinsic factors, there are patient general status, age, immunodeficiency, hereditary disorders of wound healing, and other chronic diseases. Superficial or deep wound infection should always be excluded [2]. There are general principles that allow to optimize the wound condition, ensuring adequate blood flow, correct local hydration, and the reduction in bacterial load: treat the patient’s basic pathologies, stop smoking, and the wound bed debridement. Goals for dressing management of chronic wounds include maintaining a moist environment, preventing infections, and preventing skin irritation and friction. It is now widely accepted that moist wounds heal faster than dry wounds. In a dry environment, eschar formation prevents the migration of cells to the wound bed and, consequently, tissue regeneration. The occlusion of the wound helps to maintain this microenvironment; in addition, an occlusive dressing leads to a state of local hypoxia, associated with a greater production of cytokines stimulating the extracellular matrix, the stimulation of angiogenesis, and the reduction in pain by inhibiting the production of arachidonic acid metabolites by macrophages [3]. After identifying and characterizing a lesion and correcting the modifiable intrinsic and extrinsic variables, the wound bed must be adequately prepared, removing the necrotic tissue and managing any infection, optimizing the wound mois-

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



ture, and ensuring health of the surrounding tissue. As mentioned, necrotic tissue prevents the formation of granulation tissue and therefore must be excised. Debridement is a process that occurs naturally, but if this does not happen within 72 h, another form of debridement must be taken into consideration. These options include surgical, mechanical, enzymatic, and biological methods. The presence of a suspected infection must always be excluded as it contributes to chronic inflammation and failure of wound healing. The infection can be superficial or deep: The first is generally treated in a more conservative way (disinfection with antiseptics, application of topical antimicrobials, or dressings impregnated with antimicrobials), while the second is generally managed through more thorough debridement and possibly with the administration of systemic antibiotics. It follows that the choice of an appropriate dressing is facilitated if the pathophysiological mechanisms underlying the ulcer and the properties of the various dressings available on the market are known. The correct indication for the use of a dressing or another is often not unique but almost always challenging, and usually, the clinician’s

Table 9.1  Evidence-based dressing selection

G. Turriziani et al.

experience is decisive in the choice. The clinician should choose the best dressing that fits the clinical scenario and that is acceptable in terms of patient comfort and costs, bearing in mind that there is a lack of scientific evidence for the use of many wound care products [4] (Table 9.1). The optimal dressing may be selected based on the conditions of the wound; it is also important to be aware of the changing wound environment and to be able to provide the most optimal dressing as the conditions of the wound change. Dry or desiccated wounds require hydration; wounds producing excess exudates need an absorbent dressing; infected wounds require appropriate antimicrobial agents; and wounds with necrotic tissue necessitate debridement. The ideal wound dressing has some general properties (easy to apply and maintain, cost permissive, easily stored, non-allergenic, and esthetically pleasing), facilitates healing (moist environment support, optimal temperature and pH, reduced trauma or maceration to wound edges, retention of heat, and gas exchange), and minimizes risk of infection (necrotic tissue debridement, exudate absorption, and reduced external contamination).


9  Dressing: Indications on Applications

9.2 Types of Wound Dressings Wound dressings can be classified based on several factors. A classification divides them into three groups, based on intrinsic properties: (1) dressings that facilitate autolytic debridement, in which the patient’s own phagocytic cells and autolytic enzymes remove nonviable tissue; (2) dressings that regulate the moisture of the wound; and (3) dressings that inhibit bacterial growth [5]. Another classification divides dressings into (1) moisture-retentive (i.e., film, hydrogel, hydrocolloid, foam, alginate, and hydrofiber), (2) impregnated/antimicrobial (i.e., silver, iodine, and honey), and (3) tissue-engineered (epidermal, dermal, and composite grafts). Some dressings are more absorbent, and others are ­ more moisturizing: In the first group there are foam, cotton, and acrylic fiber dressing, hydrocolloid, alginate, hydrofiber, and ceramic dressing; in the second group, there are glycerin magnesium sulfate, hydrogels, silver-based dressing, foam, and some hydrocolloid and alginate. The main dressings with their most typical indications are listed in Table 9.2.

Table 9.2 Wound indications Dressing Film



Foam Alginate


9.2.1 Gauze Gauze is a sterile dressing composed of cotton yarn and thread, used since the end of the nineteenth century, and available in both woven and nonwoven forms. Gauze quickly became the most commonly used surgical dressing, as it is inexpensive, reliable, and highly absorbent, and nowadays, it is the standard to which other wound care products are compared [6]. It is a versatile dressing, and it can be used in both infected and non-infected wounds, wounds of various sizes and shapes, and to remove exudates and prevent premature wound closure. On the other hand, woven gauze may potentially lead to wound trauma and mechanical debridement, as it requires force to remove. It follows that removal of the dried gauze may reinjure the wound, cause pain and discomfort to the patient, and delay wound healing. Furthermore, evaporation of the

Silver Iodine Tissue-­ engineered • Epidermal grafts • Dermal grafts  Xenogenic  Allogenic • Composite grafts





Main indications Minor split-thickness skin graft donor sites Minor abrasions Intravenous access sites Occlusion for topical medication to improve absorption Secondary dressings for hydrogels, foams, alginates First-degree burns Stage 1 pressure ulcer Dry vascular ulcers Coumadin-related skin necrosis Painful and non-exudative wounds Vascular ulcers Pressure ulcers Diabetic ulcers Mild-moderate burns Skin abrasions and superficial acute wounds Wounds over bony prominences Mildly exudative wounds Deep and exudative pressure ulcers Pyoderma gangrenosum Diabetic wounds Bleeding wounds Deep and exudative pressure ulcers Pyoderma gangrenosum Diabetic wounds Traumatic wounds Mild-moderate burns Superficial infections Mild burns Superficial infections Extensive burns Partial- and full-thickness wounds Vascular ulcers Pressure ulcers Surgical wounds Severe burns and burn scars Diabetic ulcers Dystrophic epidermolysis bullosa Venous ulcers Diabetic foot ulcers

wet dressing leads to cooling of the tissues, resulting in reflexive vasoconstriction, hypoxia, and impaired leukocyte activity, all contributing to impaired wound healing [7]. In addition, in vitro studies have demonstrated that bacteria readily pass through up to 64 layers


G. Turriziani et al.

of gauze and that infection rates are significantly higher in wounds using gauze compared to transparent films or hydrocolloids [8]. Despite these serious critiques of gauze as a wound dressing, there is tremendous controversy over its supposed benefits, and there is no significant scientific data that critically compare its efficacy against other dressings [9]. High-quality RCTs are necessary to accurately assess the clinical benefits and drawbacks of gauze.

polyurethane or co-polyester. They are gas and water vapor permeable, but impermeable to fluid and bacteria. By not permitting water loss, they provide a moist environment for wound healing and promote autolytic debridement. Transparency allows to monitor wound healing, without frequent removal of the dressing. Transparent film dressings have non-­absorbent properties, and this may lead to excess exudate accumulation and maceration of wound edges. Furthermore, they should not be used for infected or secreting ulcers, as the moist, and non9.2.2 Impregnated Gauze draining environment is ideal for bacterial growth. Most often, transparent film dressings are Impregnated gauze was created in order to make used in the setting of surgical incisions, superfigauze nonadherent and moderately occlusive. It is cial wounds without exudates, intravenous cathlinked with various substances such as petroleum, eter sites, and friction areas. iodine, bismuth, and zinc Impregnated gauze dressDespite their lack of absorptive properties, ings allow for increased retention of moisture in the film dressings are commonly used over skin graft wound bed and decreased desiccation or trauma donor sites. If exudates are seen to accumulate during dressing changes. It is a versatile dressing under the dressing, the fluid can be released and that can be used both as nonadherent primary dress- subsequent patch coverage with another transparings and as a contact layer on granulating wound ent film. Film dressings are also used on surgical beds when used with secondary gauze dressings. wounds following primary closure left to heal by They are often used both on the donor and secondary intention. Currently, physicians tend recipient skin graft sites and on burns, as their to use film dressings less frequently for chronic removal is without pain. Even impregnated gauze cutaneous ulcers, preferring the more advanced has negative sides. Bismuth-containing dressings modern dressings. However, they may be used as are cytotoxic and may cause an exaggerated a secondary dressing applied over other dressings inflammatory response, so they are not indicated or topical preparations. for venous insufficiency ulcers. Iodine-­ impregnated dressings are also cytotoxic: They are indicated for secreting deep and tunneling 9.2.4 Hydrogel wounds, but must be frequently changed, as the cytotoxicity of iodine may cause tissue damage. Hydrogels are complex hydrophilic organic Additionally, as impregnated gauzes have no cross-linked polymers, composed of 80–90% absorbent properties, they are not recommended water. for wounds with heavy drainage. Hydrogels are classified according to their Comparative studies between gauze and physical structure and chemical composition: impregnated gauze did not show significant differences in terms of reduced wound healing times 1. Amorphous (non-crystalline). 2. Semi-crystalline (a complex mixture of amoror costs [10]. phous and crystalline phases). 3. Crystalline.

9.2.3 Film

Transparent film dressings are thin and flexible self-adhesive sheets, most often composed of

Hydrogels are packed in tubes, spray bottles, or foil packets, and they are also available as sheet or impregnated gauze.

9  Dressing: Indications on Applications

Hydrogels have the ability to absorb a minimal amount of fluid by swelling, but they may also provide moisture to a dry wound, promoting autolytic debridement. Hydrogels promote granulation and epithelialization of the wound bed while cooling skin temperature by up to 5  °C [11]. Compared to occlusive dressings, they are more permeable to gas and water, but they are a poorer bacterial barrier. Hydrogels are typically used to hydrate wound beds and facilitate debridement. The skin adjacent to the wound needs to be protected from excessive hydration, as maceration may occur. Hydrogels are often indicated for pressure ulcers, partial- and full-thickness wounds, painful ulcer, thermal injuries, and vascular ulcers or may be considered for softening dry necrotic material. They can be used in conjunction with other topical preparations. Hydrogels can be left in place for up to 3 days and often require secondary dressings.

9.2.5 Hydrocolloid Hydrocolloids are unique two-layer dressings. The inner layer is self-adhesive and composed of hydrophilic particles such as gelatin, pectin, carboxymethylcellulose (CMC), or another elastomer. The outer layer is composed of polyurethane and seals the wound from bacteria, foreign debris, and shearing forces. Hydrocolloid dressings are sold in a multitude of sizes, and shapes and are available in a paste, powder, or granule form. When the inner layer meets fluid, such as exudate, the material swells into a gel over the wound. The gel covering creates a moist and thermally insulated environment for wound healing. Note that when hydrocolloid dressings are used, a characteristic gelatinous mass is formed on the ulcer surface. It is not purulent material. Hydrocolloid dressing has been reported to increase epidermal healing by above 40% [12]. It absorbs exudates by 20 times the weight of the pad. It facilitates autolytic debridement, pro-


motes granulation tissue and epithelialization, and even increases collagen synthesis. It does not require a secondary dressing. Hydrocolloids can be left on the wound for up to 7  days and removed once drainage is noted beneath the dressing. These dressings are regularly used for partial- and full-thickness wounds with low-to-moderate exudates, granular and necrotic wounds, minor burns, and pressure ulcers, so they are particularly useful when autolytic debridement is desirable. They are to be avoided in wounds suspected to be having anaerobic infection. Because hydrocolloid dressings are self-­ adhesive, caution should be taken in fragile skin adjacent to the wound.

9.2.6 Foam Foam dressings were developed as an alternative to hydrocolloids in 1970. They are composed of semipermeable polyurethane that is manufactured to contain air bubbles. Foam dressings are available in sheet form or as spreadable foams, generally sold as semi-occlusive dressing. They are water vapor and gases permeable, still maintaining moist wound environment, but not bacteria permeable. These dressings have absorptive properties, making them ideal for wounds with moderate-to-­ heavy exudates. They can be used on granulating or slough-covered partial- and full-thickness wounds, donor sites, ostomy sites, minor burns, and diabetic ulcers. Additionally, they can be used on infected wounds, but should be changed daily [13]. On non-infected wounds, they can be left in place for 4–7 days and changed when saturated with exudates. Maceration of the surrounding skin is seen if dressing becomes saturated. Removal of foam dressings is painless and does not reinjure the wound. Foam dressings are not ideal for dry or eschar-­ covered wounds, third-degree burns, sinus tracts, or arterial ulcers, due to their ability to further dry the wound.

G. Turriziani et al.


9.2.7 Alginate Alginate dressings are made of polysaccharide fiber, containing alginic acids, derived from various species of seaweed. These dressings were first discovered by sailors in 1880. They are highly absorbent, nonadherent, and biodegradable. When exposed to serum in a wound, the calcium and sodium ions in the dressings form a hydrophilic gel, so as to create a moist wound environment, absorb exudate, and prevent microbial contamination. Alginates are more absorbent than hydrocolloids: In fact, these products are capable of absorbing up to 20 times their weight, making them a good choice for highly exudative and draining wounds, pressure and vascular ulcers, surgical incisions, wound dehiscence, tunnels, sinus tracts, skin graft donor sites, exposed tendons, and infected wounds (Fig.  9.1). Alginates are also useful in bleeding wounds, because of their hemostatic properties. Alginate dressings are not indicated for dry wounds, as they do not provide hydration. They may be left in place for up to 7  days in a clean wound but must be changed daily in infected wounds. Alginates are not painful at dressing change and can reduce healing time as compared to other types of dressings. They are produced as sheets, ribbons, and ropes, which are used for packing deep wounds and cavities.

Despite the prevalent use of alginate dressings, few studies have reported statistically significant justification of their use in any particular type of wound. Some randomized trials have yielded conflicting data. However, it has become increasingly apparent that the secondary dressing used in conjunction with the primary alginate is of tremendous importance. For heavily exudative wounds, an absorbent pad is useful, while a semipermeable film or foam is preferred for light-to-­ moderately exudative wounds. It has been suggested that there are three primary factors when considering the use of alginate dressings: (1) chemical nature of alginate, (2) amount of fiber implanted, and (3) vascularity of tissue at site of implantation [14].

9.2.8 Hydrofiber

Hydrofiber dressings are composed of nonwoven sodium carboxymethylcellulose (CMC) fibers, which form a gel on contact with exudates. As the fibers turn into a gel, the dressing provides a moist environment for wound healing and serves as a barrier against microbes. These dressings are a good choice for heavily exudative or infected wounds. They may be kept in place for up to 7 days or until saturated. Hydrofibers are similar to alginates both in structure and in properties, even if they have 2–3 times greater absorptive capacity than alginates. Numerous studies have compared hydrofibers to alginate dressings, as both are indicated for similar wounds: Hydrofibers are preferred for their ease of application and removal, greater interval between dressing changes, and decreased costs [15]. Hydrofibers were compared to paraffin gauze dressings in the treatment of split-thickness skin graft donor sites: The use of hydrofiber is associated with less pain and faster rates of wound healing, with superior cosmetic results at 1 year [16]. CMC products can be also used in partial-­ Fig. 9.1 Antiblastic extravasation ulcer with tendon-­ thickness and small burns. muscle exposition

9  Dressing: Indications on Applications

9.2.9 Silver


Silver is a good dressing material, and it requires less frequent changes of dressings, John Woodall first described the antimicrobial which may be up to 7 days. It should be reserved properties of silver in 1617. Silver is a broad-­ for infected wounds. Silver-containing dressings are not to be used spectrum antimicrobial agent with activity against bacteria, fungi, yeast, and viruses. At in patients undergoing MRI examination. Silver higher concentrations, it is also effective sulfadiazine is not to be used in patients with against MRSA and vancomycin-resistant G6PD deficiency. It should not be used in clean enterococci (VRE) [17]. Due to silver’s exten- surgical wounds, not to be used in low-risk of sive activity, it can be found in a wide variety infections like donor site, closed surgical wounds, of dressings and products. Silver may also aid chronic wounds, and patient’s sensitivity to in reducing inflammation, which promotes silver. wound healing. To determine the optimal dosing of silver to achieve either bacteriostatic or bactericidal 9.2.10 Iodine effects, the local wound environment must be thoroughly considered. Silver has been proven to Iodine is an essential micronutrient in human be effective against superficial microbes, but its metabolism, particularly for thyroid hormones efficacy decreases in deeply infiltrating bacterial T3 and T4. Since the initial discovery of the antimicrobial properties of iodine in 1882, iodine-­ infections. While all silver dressings release silver upon based products have played important roles in the contact with fluid, they vary greatly in the rate, prevention of surgical site infections. Iodophors duration, and peak levels of silver released. To are disinfectants containing iodine and a solubiachieve an antibacterial effect, a minimum con- lizing agent that release free iodine when in solucentration between 5 and 50  ppm of silver is tion. They were developed in the 1950s as an alternative to using pure iodine, because of side needed in the wound. The antibacterial mechanism of action of sil- effects including pain and skin irritation. The ver is multifactorial. Once the silver cations are most commonly used iodophors in dressings released, they are capable of penetrating cell include povidone-iodine and cadexomer iodine. walls, inactivating bacterial enzymes, and impair- The povidone-iodine preparations were develing DNA synthesis. Resistance and allergy are oped in the 1960s and are widely used as an antiseptic in the preparation of preoperative hand always possible complications. The majority of the studies comparing silver scrubs. While not yet fully understood, it is believed dressings to other treats found no significant difference in the rates of complete healing. Despite that the antimicrobial effects are due to iodine’s a lack of quality human trial data, silver-based ability to rapidly penetrate the cell wall of products are manufactured in combination with microorganisms. With respect to the prevention and managenearly all types of dressings, including alginates, ment of biofilms, some studies have reported that collagens, creams, foams, films, hydrofibers, low-dose, slow-release iodine is effective in killhydrogels, hydrocolloids, and negative pressure ing free-floating bacteria, and they suggest iodine sponges [18]. Silver is available in dressings in different is a good choice of antiseptic dressing [19]. Controversy also exists regarding the cytotoxforms: elemental ions (silver metal and nanocrystalline silver); inorganic compounds (silver icity of iodine resulting in delayed wound healoxide, silver phosphate, silver chloride, silver ing; however, the relatively slow release of low sulfate, and silver calcium sodium phosphate); doses of iodine can improve healing rates. Slow-release iodine dressings are indicated in and organic complex (silver alginate and silver a variety of wounds with either confirmed or suscarboxymethyl cellulose).


pected infection such as pressure ulcers, venous leg ulcers, diabetic foot ulcers, minor burns, and superficial skin loss injuries. Iodine dressings should be changed when they lose their color, as that is an indicator of their antiseptic effect. Due to iodine’s critical role in metabolism and thyroid function, it is imperative to carefully supervise patients with thyroid disease and iodine sensitivity, those who are pregnant or breastfeeding, and newborns.

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well documented for burns, surgical wounds, and cutaneous ulcers [20]. Collagen-based biological dressings are divided into “naturally occurring collagen matrix” and “synthetic collagen-base dressing.” The first one consists of sheets of xenografts (porcine or bovine) that have been processed to make them suitable for use on denuded skin areas. The second one is made up of collagen that has undergone a more complex processing. A collagen matrix may serve as a skeleton or scaffolding on which the new tissue gradually 9.2.11 Tissue-Engineered Biological forms [21]. It has been suggested that attachment Dressings of fibroblasts to the implanted collagen enhances new collagen synthesis during wound healing Tissue-engineered biologic dressings are created [22]. A collagen matrix protects the ulcer and its to simulate natural scaffolding and matrices dur- surroundings from mechanical trauma and proing wound healing. These products are skin vides a moist environment. products composed mainly of cells, extracellular Some investigators suggest that the acellular matrix materials, or a combination of both. They dermis may serve as a template for dermal regencan contain living cells (living skin substitutes) eration. Some of these non-living substitutes are or not (non-living skin substitutes). These tissue-­ said to contain cytokines [23], which may render engineered dressings essentially mimic autolo- them more effective than synthetic dressings. gous skin grafts but are advantageous through Further studies are needed to obtain a more accubypassing the creation of painful donor sites. rate evaluation of their efficacy; however, the Tissue-engineered biologic dressings have been overall impression is that they do not actively studied and are used in a variety of chronic ulcer stimulate or enhance wound healing, as do living including diabetic foot ulcers, venous ulcers, substitutes. burns, surgical wounds, and epidermolysis bullosa. Living Skin Substitutes These substitutes consist of epidermal, dermal, or Non-Living Skin Substitutes composite components. They are living skin These products originally are derived from living equivalents, created to re-establish the appropritissues, but do not contain living cells when ate physiological microenvironment needed for applied to the wound. They fulfill the main pur- optimal wound repair. poses of an optimal dressing: provision of a moist Keratinocyte grafts are multi-layered stratienvironment, prevention of water loss, and pro- fied skin equivalents that very closely resemble tection against external infections or trauma. natural skin. Keratinocyte grafts are divided into Allogeneic cadaver skin may be used as a autologous [24] and allogeneic grafts [25]: The biological dressing. Devitalization of the allograft first requires a biopsy specimen from the patient’s obviates its antigenic effect. It can also be pro- skin or a sample of his/her hair follicles, and the duced as an acellular dermal matrix by the second is derived from the foreskins of newborns. removal of the epidermis and the cells in the It seems that the graft works as a semi-occlusive dermis. dressing that prevents dehydration and reduces Xenografts consist of porcine, bovine, or pain. Keratinocyte grafting does provide some equine skin. These products are presently irradi- degree of improvement in most cases, even in ated to achieve sterility. The use of xenografts is ulcers that do not heal completely. Improvement is

9  Dressing: Indications on Applications


manifested by granulation tissue formation, epiHoney is used as a dressing material for thelialization advancing from the ulcer margin, 4000 years. It is derived from many floral sources. and a significant reduction in the ulcer surface Manuka honey and pasture honey are two main area. Disadvantages include a long culture time types of honey used for dressing. The effect is (several weeks) of the keratinocytes, the fragile deodorizing and reduces inflammation, edema, nature of the graft, expense, and a short shelf life. and exudates, and it has some antibacterial effects They can be indicated in patients with deep burns. as well. Dermal grafts can be xenogeneic or allogeHyaluronic acid (HA) is a natural component neic. These dressings are typically composed of of extracellular matrix; it controls water retention collagen and additional extracellular matrix com- and ionic and molecular diffusion. HA facilitates ponents. Xenogeneic grafts are typically made the growth and movement of fibroblast. It is from porcine or bovine collagen. Depending on available as cream, sponge, fibers, and threads. It the characteristics of the matrix, they can be used is also used as a scaffold for fibroblast and keratiin severe burns, vascular or pressure ulcers, and nocyte culture. partial- or full-thickness wounds. Allogeneic Collagen dressings are made of collagen grafts are composed of cadaveric dermis or neona- extracted from rat tendon, bovine skin, or pig tal foreskin, so they can trigger antigenicity and intestine. They are available in the form of powrejection of the graft. These grafts undergo biodeg- der, cream, and sheet or wafers, or in combinaradation after a period of 3–4 weeks, providing the tions with alginates, metronidazole, mupirocin, wound with time for in-growth of blood vessels, gentamycin, and silver sulfadiazine. Collagen is and fibroblast and keratinocyte proliferation. thought to work as a scaffold for cells involved in Typical indications are full-­ thickness diabetic repair process and for the proteolytic enzymes ulcers and wounds related to dystrophic epider- present in chronic wounds. The whole process molysis bullosa. reduces the chronic inflammatory stage of the Composite grafts are bilayer tissue-­wound. Collagen dressing is not a debriding engineered skin equivalents, composed of human agent or an antiseptic: It can be used in chronic keratinocytes (epidermal layer) and bovine col- and exudating wounds, without infection or lagen with fibroblasts (dermal layer). These prod- necrotic tissue. ucts increase the rate of healing when compared Hydroconductive dressing, charcoal dressing, with traditional dressings [26]. Venous ulcers and polyhexamethylene biguanide dressing, pH-­ full-thickness diabetic foot ulcers are the main modulating dressing, and hemoglobin spray are indications. other possible products that can be used for wound care.

9.2.12 Other Types of Dressings Silicone dressings can be used for hypertrophic and keloid scars instead of pressure garments. Over time, silicone dressings are able to soften the scar tissue, allowing for a decrease in the height of the hypertrophic scar [27]. It seems that the dressing prevents water vapor loss, increasing hydration of the scar. Silicone dressings have continued to become more widely used, as it has a non-traumatic adhesive component, which makes dressing changes less painful.

9.3 Negative Pressure Wound Therapy (NPWT) Negative pressure wound therapy (NPWT), or topical negative pressure (TNP), has gained widespread use from the vacuum-assisted closure technique (VAC™; Kinetic Concepts Inc., San Antonio, TX) that applies localized negative pressure to the wound bed through a polyurethane reticulated open-cell foam dressing or a polyvinyl alcohol foam dressing [28].

G. Turriziani et al.


The mechanisms of action are not completely understood, though the biophysical and biochemical effects are important. The technique is based on delivering topical negative pressure through a material that is applied to a wound. NPWT is effective because it removes exudates and debrides, increases blood perfusion by neovascularization, leads to the formation of granulation tissue, and increases the local circulation of antibiotics into the wound bed [29]. The microdeformations induced by the application of sub-atmospheric (negative) pressure through the foam dressing are instrumental in regulating granulation tissue formation. The reduction in  local and interstitial tissue edema, the increased perfusion of the peri-wound area, the changed bacterial composition, and the mechanical stimulation of the wound bed contribute to the clinical success of the NPWT. The VAC therapy system seems to be a safe and effective treatment for complex diabetic foot wounds and could lead to a higher proportion of healed wounds, faster healing rates, and ­potentially fewer re-amputations than standard care [30]. Most evidence supports the effectiveness of NPWT on chronic leg ulcers and post-traumatic ulcers. Moreover, there is a significant benefit of VAC therapy after skin grafting in chronic leg ulcer patients [31]. NPWT is recommended in contaminated or colonized shallow wounds with no exposed bone or foreign body. It can also be used either in wounds with low risk of infection or in infected wounds (Fig. 9.2a, b). The use of NPWT requires careful preparation of the wound bed, so debridement is an essential initial step (Fig. 9.3a–d). The usefulness of NPWT in other types of chronic wounds such as vasculitic ulcers or malignant wounds has yet not been studied systematically. There is some causal evidence for the use of NPWT in pyoderma gangraenosum as an adjunct to immunosuppressive treatment [32]. Continuous NPWT delivered at −125 mmHg has been recommended, despite consistent research findings suggesting potential advantages



Fig. 9.2 (a) Scrotal ulcer in a patient with Fournier’s gangrene. (b). After treatment with absorbent dressings, subsequently VAC therapy, and dermal substitute

to the use of lower pressures and intermittent therapy. For home treatment with NPWT, a systematic education of patients and relatives is necessary to ensure the same level of efficacy and safety as in the hospital setting. NPWT has high material costs; however, these are compensated by the lower number of time-­ consuming dressing changes and the shorter duration until the wound is “ready for the surgery.” NPWT appears to be a safe treatment, and serious adverse events have been rarely reported. NPWT adverse effects include discomfort, pain, and excessive tissue growth into the dressing. Complications are limited if the device is used properly.

9  Dressing: Indications on Applications






Fig. 9.3 (a) Ulcer secondary to septic embolism. Pre-­ ings. Subsequent application of VAC therapy for stimuladebridement. (b) After surgical debridement. Treatment tion of the granulation tissue. (c) 5 days after split-thickness with enzymatic debridement and with absorbent dress- skin graft. (d) 3 weeks after skin graft

9.4 Conclusions A large variety of dressing materials are currently available, and new dressings with specific and mixed properties will be continually created thanks to technological advancement. Despite the abundance of therapeutic options, it is apparent that few high-quality RCTs have been performed to evaluate wound dressings, with even fewer demonstrating a clear-cut benefit of a particular dressing or treatment modality. Until new data are received, clinicians must continue to systematically evaluate, categorize, and treat each wound using the guiding principles of debridement, managing exudates, and preventing microbial colonization. Each type of ulcer should be treated with the most appropriate dressing material. The ulcer’s clinical appearance

is the main parameter in determining the most suitable dressing.

References 1. Gurtner GC, Werner S, Barrandon Y, Longaker MT.  Wound repair Regen. Nature. 2008;453(7193):314–21. nature07039. 2. Gantwerker EA, Hom DB. Skin: histology and physiology of wound healing. Facial Plast Surg Clin North Am. 2011;19(3):441–53. 3. Kirschner CM, Anseth KS.  Hydrogels in healthcare: from static to dynamic material microenvironments. Acta Mater. 2013;61(3):931–44. https://doi. org/10.1016/j.actamat.2012.10.037. 4. Jones RE, Foster DS, Longaker MT. Management of chronic Wounds-2018. JAMA. 2018;320(14):1481–2. PMID: 30326512

100 5. Ayello EA, Cuddigan JE.  Debridement: controlling the necrotic/cellular burden. Adv Skin Wound Care. 2004;17(2):66–75. 6. Broughton G 2nd, Janis JE, Attinger CE. A brief history of wound care. Plast Reconstr Surg. 2006;117(7 Suppl):6S–11S. 7. Ovington LG.  Hanging wet-to-dry dressings out to dry. Home Healthc Nurse. 2001;19(8):477–83. 8. Lawrence JC. Dressings and wound infection. Am J Surg. 1994;167(1A):21S–4S. 9. Vermeulen H, Ubbink D, Goossens A, de Vos R, Legemate D. Dressings and topical agents for surgical wounds healing by secondary intention. Cochrane Database Syst Rev. 2004;2:CD003554. 10. Ubbink DT, Vermeulen H, Goossens A, Kelner RB, Schreuder SM, Lubbers MJ.  Occlusive vs gauze dressings for local wound care in surgical patients: a randomized clinical trial. Arch Surg. 2008;143(10):950–5. 11. Ovington L. The well-dressed wound: an overview of dressing types. Wounds. 1998;10(Suppl A):1A–11A. 12. Klasen HJ. A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver. Burns. 2000;26:131–8. 13. Seaman S. Dressing selection in chronic wound management. J Am Podiatr Med Assoc. 2002;92(1):24–33. 14. Thomas S.  Surgical dressings and wound management. Cardiff, South Wales: Medetec Publications; 2010. 15. Robinson BJ.  The use of a hydrofibre dressing in wound management. J Wound Care. 2000;9(1):32–4. 16. Barnea Y, Amir A, Leshem D, Zaretski A, Weiss J, Shafir R, Gur E. Clinical comparative study of aquacel and paraffin gauze dressing for split-skin donor site treatment. Ann Plast Surg. 2004;53(2):132–6. 17. Warriner R, Burrell R.  Infection and the chronic wound: a focus on silver. Adv Skin Wound Care. 2005;18(Suppl 1):2–12. 18. Tomaselli N. The role of topical silver preparations in wound healing. J Wound Ostomy Continence Nurs. 2006;33(4):367–78. 19. Durani P, Leaper D. Povidone-iodine: use in hand disinfection, skin preparation and antiseptic irrigation. Int Wound J. 2008;5(3):376–87. 20. Davis DA, Arpey CJ. Porcine heterografts in dermatologic surgery and reconstruction. Dermatol Surg. 2000;26:76–80.

G. Turriziani et al. 21. Burke JF, Yannas IV, Quinby WC Jr, et al. Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Ann Surg. 1981;194:413–28. 22. Postlethwaite AE, Seyer JM, Kang AH. Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. Proc Natl Acad Sci U S A. 1978;75:871–5. 23. Voytik-Harbin SL, Brightman AO, Kraine MR, et  al. Identification of extractable growth factors from small intestinal submucosa. J Cell Biochem. 1997;67:478–91. 24. O’Connor NE, Mulliken JB, Banks-Schlegel S, et  al. Grafting of burns with cultured epithelium prepared from autologous epidermal cells. Lancet. 1981;1:75–8. 25. Teepe RG, Keobrugge EJ, Ponec M, et al. Fresh versus cryopreserved cultured allografts for the treatment of chronic skin ulcers. Br J Dermatol. 1990;122:81–9. 26. Jones JE, Nelson EA, Al-Hity A.  Skin grafting for venous leg ulcers. Cochrane Database Syst Rev. 2013;1:CD001737. https://doi. org/10.1002/14651858.CD001737.pub4. 27. Perkins K, Davey RB, Wallis KA. Silicone gel: a new treatment for burn scars and contractures. Burns Incl Therm Inj. 1983;9(3):201–4. 28. Expert Working Group. Vacuum assisted closure: recommendations for use. A consensus document. Int Wound J. 2008;5(Suppl 4):iii–19. 29. Lo Torto F, Ruggiero M, Parisi P, Borab Z, Sergi M, Carlesimo B.  The effectiveness of negative pressure therapy on infected wounds: preliminary results. Int Wound J. 2017;14(06):909–14. 30. Hinchliffe RJ, Valk GD, Apelqvist J, Armstrong DG, Bakker K, Game FL, Hartemann-Heurtier A, Löndahl M, Price PE, van Houtum WH, Jeffcoate WJ. A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2008;24(Suppl 1):S119–44. 31. Körber A, Franckson T, Grabbe S, Dissemond J.  Vacuum assisted closure device improves the take of mesh grafts in chronic leg ulcer patients. Dermatology. 2008;216:250–6. 32. Geller SM, Longton JA. Ulceration of pyoderma gangrenosum treated with negative pressure wound therapy. J Am Podiatr Med Assoc. 2005;95:171–4.

Dressing in Burns


Antongiulio Mangia, Agostino Rodda, and Antonio Di Lonardo

10.1 Introduction

Full-thickness burns involve entirely the dermis and extend deep into subcutaneous tissue. Burn wound healing depends on the depth and These wounds are insensitive to light touch and surface involved, cause of damage (thermal, pinprick, usually have a dry and white appearchemical, or electric), general condition of the ance, and should be excised and grafted patient, and associated comorbidities; therefore, (Fig. 10.1). Autologous skin grafting (autografts) the first evaluation of wound dressing approach is still the first choice for treatment and involves requires an initial assessment of the burn based the transplantation of healthy skin from the on depth, extent, and anatomical site [1, 2]. patient’s undamaged donor site to cover the wound site. Autograft can be harvested full-­ thickness, consisting of epidermis and dermis or 10.2 Full-Thickness Burns split-thickness, consisting of the epidermis and upper part of the dermis. Despite the possibility Burn injury may involve one or both skin layers of amplification of the graft with meshes, lack of and may extend deep into the subcutaneous fat, unharmed skin in a severely burned patient conmuscles, and even bony structures. Deep partial-­ stitutes therefore a concrete limitation to the thickness (dermal burns), extending into the autograft; furthermore, deep burns or presence of reticular dermis, generally will take three or more weeks to complete healing process. When pressure is applied to the burn, capillary refill appears slow or absent. By the second day, the wound may be white-colored and is usually fairly dry. As a rule, deep partial-thickness burns that would not heal within 3  weeks should be completely excised and grafted. A. Mangia · A. Di Lonardo (*) U.O.C. Burn Center A.O.U. Pisana, University of Pisa, Pisa, Italy e-mail: [email protected] A. Rodda Plastic Surgery Clinic, ASUGI, University of Trieste, Trieste, Italy

Fig. 10.1 Full-thickness burn of legs with areas of carbonization

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



infected tissue do not predispose to autograft, and in these cases, coverage with skin substitutes should be considered, with allo- or xenograft or advanced dressings. Skin substitutes could protect large burn wounds when donor skin is limited, enhancing wound healing and reducing inflammatory responses and subsequent scarring [3].

A. Mangia et al.

thickness autograft and guaranteeing an equal thickness to the autograft one, minimizing at the same time scarring contracture [9]. The dermal matrix is able to support fibroblast infiltration, keratinocyte migration, and neo-­ vascularization as well [10]. 4. Biosynthetic wound dressings: These are increasingly employed in superficial and moderate-depth partial burns, aiming to cover the wound and optimize healing in terms of 10.2.1 Skin Substitutes time, pain, complications, and costs. Dermal and epidermal substitutes can be applied to Skin substitutes can be categorized into biologisuperficial and partial depth burns, able to cal ones, synthetic substitutes, or a combination guarantee a rapid dermal regeneration associof both. ated with proper wound coverage and protecBiological substitutes can be further categotion [11]. rized into: Bilayer-composed dressings can be applied for partial depth burns management: The inner 1. Allografts: The cadaveric skin graft is a stanlayer, for example, made of xenogeneic matedard biomaterial for temporary skin replacerials (e.g., Porcine collagen [12] and bovine ment in burn patients. Cadaveric skin is able collagen [13]) is able to stimulate wound healto implement wound bed preparation before ing, while the outer layer, usually an impermeautograft placement and can decrease pain able silicone film, is able to control moisture and wound infection rates. Other benefits of loss from the wound and prevent infections, the cadaver allograft are represented by reducremaining pervious to gases and transparent tion in fluid, electrolyte, and protein loss, for a better wound evaluation. Adherence to together with energy requirements. This graft the wound is to be achieved, by careful fixing also prevents tissues from desiccation, stimuand movement reduction, to prevent dressing lates epithelialization, prepares wounds for shearing from the wound surface and provide definitive closure, and provides a dermal temmechanical coverage [14]. These medications plate for epidermal grafts [4–6]. Disadvantages are provided in sheets, which can be cut of the cadaver skin include serious infectious according to the wound shape, and are to be disease risks (such as HIV and hepatitis, firmly applied and fixed, eventually using transmitted to the recipient patient) and a stitches; however, there are bilaminate biosynrejection time between 7 and 14 days due to thetic dressings provided in glove shape different complexes of histocompatibility by (Fig.  10.2), with specific indication on hand the host [7]. localized superficial or partial deep burns and 2. Xenografts: Graft is harvested from animals scalds. The latter, produced in different sizes and used to replace lost skin. Despite a large to fit both adults and pediatric patients, are availability compared to allograft, they have a able to reduce both healing time and pain shorter rejection time and produce greater (Figs. 10.3 and 10.4), providing easier fitting inflammation [8]. and less bulky dressings [15]. 3. Natural scaffolds, such as de-cellularized and Furthermore, these dressings need a caudermal human matrix: These materials are tious selection of wound application, as previcomposed of a mixture of dermal elastin and ous accurate debridement shall be performed, collagen, free of cellular components, and and possible infection evaluated, in order to their use can be associated with ultra-thin prevent delayed healing and the need for fursplit-thickness grafts (0.1–0.2  mm), thus ther surgery; high costs have to be taken into avoiding donor site morbidity of split-­ consideration.

10  Dressing in Burns

Fig. 10.2  Superficial partial-thickness  burn of the back hand

Fig. 10.3  Biosynthetic wound dressing constructed of a silicone film with a nylon fabric with collagen in a glove shave


In addition, tridimensional hyaluronic acid ester matrix bilayer dressings can be used on deep and chronic wounds, but also for the adequate management of deep and partial depth burns, associated with massive tissue loss where healing process has dropped, preparing adequate tissues for skin grafting [16]. 5. Cultured scaffolds, such as cultured epithelial graft, autologous cultured fibroblasts, and keratinocytes. In some massively burned patients the burns are so extensive that donor site availability is limited and human epidermal cells from a small skin-biopsy sample can be cultured to produce coherent epithelial sheets. Nevertheless, the production of a thin sheet of epithelial cells with high production costs and risk of ulceration must be considered [17]. 6. Allogenic amnion, derived from fetal membrane, can be particularly effective if applied on partial-thickness burn wounds; it can be used as protective dressing, guaranteeing the preservation of wound bed in prevision of secondary skin grafting coverage. Allogenic amnion is fragile and difficult to handle and needs sterilization processes in order to cut off biological transmission probability, as it is contaminated by definition [18].

10.3 Partial-Thickness Burns 10.3.1 Superficial Burns

Fig. 10.4  Biosynthetic wound dressing application and removal at 14  days with complete re-epithelialization below

Burns involving only the epidermis are erythematous and very painful, however do not form blisters. Most sunburns fit this category of superficial, epidermal injury. Within 3–4 days, the dead epidermis sloughs and is replaced by regenerating keratinocytes. Many different ointments can be applied on this type of lesion after accurate cleansing, based on antibacterial principles; silver sulfadiazine, for example, can be applied for bacteriostatic action and able to alleviate pain as well [19]; preparations containing these substances are to be applied with a 1–2  mm layer on the wound daily, until complete re-epithelialization.

A. Mangia et al.


10.3.2 Superficial Partial-Thickness Burns Superficial partial-thickness burns extend instead into the papillary dermis and characteristically form blisters. Once the blister is removed from a superficial partial-thickness burn, the wound shows up pink, wet, and hypersensitive to touch. With appropriate wound care, superficial dermal burns usually heal within 2–3 weeks, without risk of scarring, furthermore do not require operation. Superficial dermal burns or graft donor site have a raw area of the body lacking epithelial covering; topical antibacterial agents are not necessary [20] and require instead epithelium reconstitution through a re-epithelializing ointment, hydrogel, or alternative coverage with advanced dressings.

Fig. 10.6  Evacuation of vesicles with leakage of serous

blisters, either intentionally or unintentionally. Another valid reason to de-roof is that large vesicles impede the mobility and comfort of the patient [21]. Theoretically, de-roofing with modern dressing application, when available, seems 10.3.3 Blister Management to be the safest and most convenient choice: This helps avoid a deep-dermal burn hidden under Management of blisters is a complicated issue. vesicles, which might lead to esthetic problems Most guidelines and studies recommend de-­ as well. Modern dressing treatment or biological roofing of blister, followed by its coverage with membranes lead to the best quality of healing and biological or modern dressing, as this was associallow for excellent mobilization of the patient ated with better recovery. One valid advantage of and his/her burned areas too. When modern de-roofing blisters is the possibility to visualize dressings or biological membranes are not availand assess the wound, as in some cases vesicles able, snipping blisters open seems to be the next might hide a deep dermal burn underneath best alternative. This shares the advantages of de-­ (Figs. 10.5 and 10.6). Moreover, it is very comroofing in not impeding movement and in reducmon for patients to present with already sheared ing pain, and at the same time, it gives a “biologic” dressing that ensures the best moisture and sealing effects. Applying an antimicrobial cream with an interface ensures the prevention of infection and mechanical trauma during fluffy dressing change.

10.3.4 Hydrogel Dressings

Fig. 10.5  Vesicles with serous content on superficial partial-thickness fluid burns

Advanced wound treatment is often based on controlled delivery of active substances into the burn site. Hydrogels are widely available on the market as the most ideal wound dressings with numerous advantages for burn wounds, including the ability to provide a moist and cooling environment (beneficial for burn wounds) non-­

10  Dressing in Burns

adhesiveness to wounds and the ability to absorb excess wound exudates. Additionally, hydrogels’ high-water content mimics the physiological wound conditions, favoring tissue regeneration with excellent biocompatibility, and the capability to encapsulate a variety of antimicrobial drugs. Clinically, hydrogels are used as wound debridement agents, moist dressings, and components of wound treatments. In burn wound management, hydrogels act as a moisture donor and can accelerate wound healing through autolytic debridement and moisture regulation [21]. While many natural hydrogels have inherent antimicrobial properties (e.g., chitosan, β-chitin, cellulose, and dextran), many have been loaded with synthetic antibiotics and antibacterial agents including metal-ion loaded hydrogels, metallic-­ nanoparticle, AMP-based hydrogels, and natural polymer-based hydrogels bearing synthetic antimicrobials [22]. Biopolymers have been utilized for their development due to their non-toxic, biodegradable, and biocompatible properties. Hydrogels have been prepared from biopolymers such as cellulose and chitosan, by crosslinking with selected synthetic polymers resulting in improved mechanical, biological, and physicochemical properties. Although biopolymer-based hydrogels present interesting features in the series of in  vitro and in  vivo studies reported for wound management, very few of them have reached clinical trials [23].


pathogenic organisms at the same time, without interfering with wound healing [24]. Indications are multiple, starting from increased infection risk wounds, various etiologies ulcers, oncology wounds, and burns. Specifically, hydrofiber dressings can be applied to superficial dermal burns, creating a moist environment able to absorb wound exudates and prevent tissue infection by stimulating the formation of collagen and re-epithelization (Figs. 10.7, 10.8 and 10.9). Hydrofiber dressing may be left in place for up to 14 days if adhered, eventually covered with

Fig. 10.7  Deep and superficial partial thickness burns of thigh without fibrin

10.3.5 Hydrofiber Dressings Fig. 10.8 Application of carboxymethylcellulose to

Hydrofiber technology, based on sodium car- areas of dermal burn boxymethylcellulose layers eventually associated with the use of ionic silver, a proven broad-­ spectrum microbial, produces a high-absorbing and soft wound coverage medication, able to remove non-viable tissue from the area, controls bacterial infection, and supports the healing process at the same time. Hydrofiber dressings, as a matter of fact, are able to absorb biofilm and prevent its formation, create a barrier protecting the wound bed, and kill Fig. 10.9 Removal of sheet and underlying reepithelialization


secondary absorbing dressings, as they guarantee a vertical absorption of exudate, avoiding maceration. If the dressing is not adherent or saturated, it should be removed and replaced. The evaluation of hydrofiber dressings adherence and wetness during the first days may also be taken into consideration for the burn deepness assessment. These medications shall not be used on sensitive or allergic to carboxymethylcellulose, nylon, or silver, when associated, with individuals.

10.3.6 Alginates Alginate dressings, originally derived from brown seaweed and so composed of polymers of alginic acid, are able to provide a soft and flexible high-absorbing medication (can absorb up to 20 times their own weight in fluid). When in contact with wound exudate, they form a gel, which can be easily removed by soft irrigation, guaranteeing normal healing processes and atraumatic dressing changes. It can be associated with other materials, particularly with silver as antibacterial adjuvant, or psyllium fibers, which can contribute to swelling absorption. Alginates are indicated for moderate to large amounts of exudate production wounds and can be left in place until 4 days, shall be changed if saturated and fully gelled. The same application can be used for donor site of autograft, using the

Fig. 10.10  Complete re-epithelialization at day 14 under removal of the adherent alginate sheet

A. Mangia et al.

hemostatic and absorption properties of the alginates, which are left in place until complete re-­ epithelialization (in this case the removal of the alginate is quite easy) or in case of poor adhesion to the tissue due to excess exudate with transformation into gel (Fig. 10.10). Alginates shall not be used on dry or necrotic wounds, like deep burns in this case, as in the absence of exudate no gel can be formed, and thus no moist healing environment.

10.4 Deep Partial-Thickness Burns Deep partial-thickness burns are characterized by loss of whole-thickness epidermis and part of dermis; thus, complete barrier loss makes these areas more prone to contamination and infection. It is therefore of utmost importance to completely seal these wounds in order to prevent infection and promote healing processes [25, 26]. Raw areas are considered always contaminated, due to the absence of mechanical skin barrier and sweat and bacterial commensals presence, both of which inhibit many pathogens. Therefore, cleansing through pressurized irrigation is of utmost importance to wash away these bacterial contaminants and debris. After cleansing, if necrotic tissue is still present, debridement can be performed by surgical, autolytic, or enzymatic methods. The most difficult management decision involves partial-thickness burns that are intermediate in depth. These burns are more aptly called “indeterminate” burns, as their healing potential becomes evident with serial assessments over several days, and require careful specialist evaluation for the possibility of bromelain-based type of enzymatic debridement; its advantages, compared to the standard of care, include decreased surgical morbidity and blood loss, length of hospital stay, rates of infection, need for skin grafting, and costs [27, 28]. More importantly, this product permits eschar removal without sacrificing viable or healthy tissue, returning entirely vital dermal or subcutaneous tissue.

10  Dressing in Burns

Autolytic debridement is exploited when surgery is not suitable for the wound type. It is not only a natural process occurring at some level in all wounds, but also highly selective, involving macrophages and proteolytic enzymes that liquefy and separate necrotic tissue from healthy one [23]. The use of proteolytic enzymes, in particular collagenase, possibly associated with antibiotics, is well documented in the topical treatment of ulcers and burns, where a surgical approach is not deemed practical. Topical collagenase preparations, available for necrotic tissue debridement from ulcers and burns, contain the proteolytic enzyme ­collagenase, derived from Clostridium histolyticum; this enzyme digests denatured collagen, which is the principal constituent of necrotic tis-

Fig. 10.11 Superficial partial-thickness burns of the back of the foot


Fig. 10.13  Application of petrolatum gauze

sue, and destroys the strands of endogenous collagen, which tend to anchor necrotic residues to the bed of the lesion. After the ointment application, it is helpful to cover the wound with a nonadherent gauze, a sterile dressing of paraffin-based tulle, formed by an open weave gauze (Figs. 10.11, 10.12 and 10.13) with a low adherence and allows free drainage of the wound, by permitting the passage of exudate to an absorbent secondary dressing; it also prevents the sterile covering gauze adhesion directly on the de-­ epithelialized area, which causes pain and removal of the newly formed epidermis. Paraffinbased tulle is not medicated and is therefore ideal for use in association with local antiseptics or antibiotics. Alternatively, other medications can be applied, like white petrolatum-impregnated fine mesh or porous mesh gauze, or 10x10  cm gauze impregnated with 4 g of 2 mg hyaluronic acid sodium salt cream, or again specific extract of Triticum vulgare impregnated gauze [29]. The dressing is then covered by a sterile gauze and can be held in place with a gauze bandage wrapped, applying sufficient tightness to hold the gauze in place but not so tightly as to impede circulation.

10.5 Facial Burns

Fig. 10.12  Application of collagenase ointment

For practical reasons, most facial burns are treated without dressing. These wounds may also be treated without topical medication, allowing

A. Mangia et al.


the involved area to dry and form a crust. Because the dry wound is often uncomfortable and heals more slowly than moist wounds, many physicians prefer to use a thin layer of bland ointment combined with a topical antibiotic [30]. The ointment is applied to the wound after gentle cleansing with water once or twice daily, or more frequently as needed, particularly in a dry climate. Bacitracin has activity against gram-­ positive bacteria. Occasionally, it may cause contact dermatitis that impedes wound healing. Alternatively, already used for more than 40 years, silver sulfadiazine 1% is considered as standard therapy for conservative treatment of burn wounds [31]. Silver nitrate and silver sulfadiazine have been widely used in wounds topical chemoprophylactic treatment, especially for burns and ulcers. Topical application of silver-­ containing agents can result in localized argyria, as well as systemic side effects in cases of greater skin areas involved. Silver sulfadiazine should be applied to small burn areas of the face and for acute treatment, in order to avoid side effects of local argyria or antibiotic resistance [32].

10.5.1 Burn Cleansing Cleansing with gentle washing is the first and most important step of burn wound care. Burn wounds should be cleansed to remove any debris or contamination, reducing the risk of infection or biofilm formation. A Cochrane review did not find any evidence that saline is superior to tap water for cleansing acute traumatic wounds, although the review did not specifically take into consideration burn wounds [33]. In a systematic review performed by Cooper et  al., three trials mentioned that saline is significantly more advantageous than tap water [34]. Hospital water supplies are, as a matter of facts, commonly colonized with Pseudomonas Aeruginosa: Therefore, filtered tap water is preferable, and this last can be achieved by point-of-use water filtration devices. A difference must be made regarding hydrotherapy, useful for removing skin necrosis, predominantly applied using tap water, but also

Fig. 10.14  Hydrotherapy tub

antiseptic solutions, which are preferred after the initial acute period when burn wounds are more likely to be colonized by various microorganisms (Fig. 10.14). Wound cleansing is an important step regarding infection prevention and treatment, contributing to initial wound healing processes as well. Irrigation, even if it is as effective as swabbing, has proven to be significantly more satisfactory to patients. Regarding clean wounds (and most burns are clean), cleansing should be performed as gently as possible to avoid the injury of the lower layers of epidermis, responsible for regeneration and healing. On the other hand, in heavily contaminated or infected wounds, cleansing should be performed aggressively, thoroughly, and as frequently as possible to eliminate biofilm. Antiseptics are used for clinically infected wounds to slow or halt the spreading of infection; however, they may also be applied on wounds that do not display clear signs of infection, in order to prevent its onset. Some examples of applicable antiseptics are: • Hypochlorous solutions: They (0.5% solution of unbuffered sodium hypochlorite) have been recognized as effective antiseptic agents for wounds. • Dakin’s solution: It is a buffered solution of 0.5% NaOCl, but is cytotoxic to keratinocytes and fibroblasts.

10  Dressing in Burns

• Acetic acid (AA): It is another antiseptic solution that has been applied as a topical antimicrobial agent to wounds, including burns. • A few heterogeneous studies involving a limited number of grossly contaminated or infected wounds suggest that 1–5% AA solutions have been effective; however, pain, itching, and burning of the skin have been reported when this concentration range has been applied. There are no clinical studies of AA use in burn patients. One in vitro study found that 3% AA was bactericidal against a broad range of burn wound pathogens [35]. • Povidone-iodine and chlorhexidine solutions have been used as topical antiseptic agents on burn wounds. Both agents are effective against a wide range of bacteria and fungi. • Presently, both agents are commonly used as soap solutions to clean wounds, especially as a “prep” of the skin, and burn wounds prior to surgery. • Chlorhexidine diphosphanilate cream: It has been tested in burn patients, and the agent is though difficult to apply and painful at concentrations above 0.5% [36].

10.6 Chemical Burns Chemical burn injuries represent only 3% of all burns; many compounds have the potential to induce chemical burns due to exposure to industrial or household cleaning substances or pesticides. Most commonly affected body areas are face, eyes, and extremities. All burn wounds, whether due to chemical or thermal sources, have in common protein denaturation, as changes in pH or dissolution of surrounding lipids may stabilize a protein and disrupt its function. Severity of a chemical burn injury is determined by several factors: • • • • • •

Concentration of chemical agent. Quantity of chemical agent. Manner and duration of skin contact. Extent of penetration. Mechanism of action. Phase of agent (liquid, solid, and gas).


Within these groups, there are different categories of compounds. Chemical burns are often described as acidic or alkaline [37, 38]. Acids act as proton donors in the biological system, and strong acids have a pH   11.5 [39]. In general, alkaline materials cause more injury than acidic compounds. Acids cause coagulation necrosis with protein precipitation, whereas the reaction to alkali is “liquefaction” necrosis, allowing the substance to penetrate deeper into the injured tissue [40]. Most important aspects of first aid for chemical burns involve agent removal from contact with the patient. This requires the removal of all potentially contaminated clothing and copious irrigation. Irrigation of chemical burns requires the protection of healthcare providers, in order to prevent additional injuries. Immediate copious irrigation has been shown to reduce the extent and depth of injury, especially to eyes [41]. Thirty minutes to 2 h of lavage may be necessary. The use of neutralizing agents is discouraged. The practical problems encountered with their use are exothermic reactions causing further thermal damage. Regional poison control centers for household chemicals or unidentified agents can be valuable resources for potential systemic toxicity and side effects of a particular agent.

References 1. Institute of Medicine. Clinical practice guidelines we can trust. Washington, DC: The National Academies Press; 2011. p. 16. 2. Leon-Villapalos J, Barret JP. Surgical Repair of the Acute Burn Wound: Who, When, What Techniques? What Is the Future?. J Burn Care Res. 2023:44. 3. ISBI “Practice Guidelines for Burn Care” ISBI Practice Guidelines Committee; Steering Subcommittee; Advisory Subcommittee. 4. Sarkar A, Rakshit P, Majumdar BK, et  al. Use of cadaveric skin allograft in management of deep burn wounds: our experience. Int J Basic Appl Med Sci. 2013;3:186–8. 5. Obeng MK, McCauley RL, Barnett JR.  Cadaveric allograft discards as a result of positive skin cultures. Burns. 2001;27:267–71. 6. Kua EH, Goh CQ, Ting Y, Chua A, Song C. Comparing the use of glycerol preserved and cryopreserved allo-

110 genic skin for the treatment of severe burns: differences in clinical outcomes and in vitro tissue viability. Cell Tissue Bank. 2012;13:269–79. 7. Böttcher-Haberzeth S, Biedermann T, Reichmann E. Tissue engineering of skin. Burns. 2010;36:450–60. 8. van Zuijlen P, et  al. Tissue engineering in burn scar reconstruction. Burns Trauma. 2015;3:18. 9. Tang B, Zhu B, Liang Y-Y, Bi L-K, Chen B, Hu Z-C, Zhu J-Y. Early escharectomy and concurrent composite skin grafting over human acellular dermal matrix scaffold for covering deep facial burns. Plast Reconstr Surg. 2011;127(4):1533–8. 10. Stephen L, David H, Maureen H, Yvelle A, Abhijit N.  Transplanted acellular allograft dermal matrix: potential as a template for the reconstruction of viable dermis. Transplantation. 1995;60(1):1–9. 11. The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. “Dressings for superficial and partial thickness burns (Review)” 2013. 12. Whitaker IS, Worthington S, Jivan S, Phipps A. The use of biobrane by burn units in the United Kingdom: a national study. Burns. 2007;33:1015–20. 13. Vana LPM, Battlehner CN, Ferreira MA, Caldini EG, Gemperli R, Alonso N.  Comparative long-term study between two dermal regeneration templates for the reconstruction of burn scar contractures in humans: clinical and histological results. Burns. 2020;46(3):596–608. 14. Whitaker IS, Prowse S, Potokar TS. A critical evaluation of the use of Biobrane as a biologic skin substitute: a versatile tool for the plastic and reconstructive surgeon. Ann Plast Surg. 2008;60:333–7. 15. Busche MN, et  al. Der Biobrane®-Handschuh bei Verbrennungen der Hand. Handchir Mikrochir Plast Chir. 2009;41:348–54. 16. Gravante G, Delogu D, Giordan N, Morano G, Montone A, Esposito G. The use of Hyalomatrix PA in the treatment of deep partial-thickness burns. J Burn Care Res. 2007;28(2):269–74. 17. Auxenfans C, Shipkov H, Bach C, Catherine Z, Lacroix P, Bertin-Maghit M, Braye F. Cultured allogenic keratinocytes for extensive burns: a retrospective study over 15 years. Burns. 2014;40(1):82–8. 18. Kesting MR, Wolf K-D, Hohlweg-Majert B, Steinstraesser L.  The role of allogenic amniotic membrane in burn treatment. J Burn Care Res. 2008;29(6):907–16. 19. Ang ES, Lee ST, Gan CS, See P, Chan YH, Ng LH, Machin D. The role of alternative therapy in the management of partial thickness burns of the face--experience with the use of moist exposed burn ointment (MEBO) compared with silver sulphadiazine. Ann Acad Med Singap. 2000;29(1):7–10. 20. Berry MG, Goodwin TI, Misra RR, Dunn KW. Digitisation of the total burn surface area. Burns. 2006;32:684–8.

A. Mangia et al. 21. Zhang W, et  al. Catechol-functionalized hydrogels: biomimetic design, adhesion mechanism, and biomedical applications. Chem Soc Rev. 2020;49:433–64. 22. Kopecki Z.  Development of next-generation antimicrobial hydrogel dressing to combat burn wound infection. Biosci Rep. 2021;41:2. 23. Alven S, Aderibigbe BA.  Chitosan and cellulose-­ based hydrogels for wound management. Int J Mol Sci. 2020;21(24):9656. 24. Richetta AG, Cantisani C, Li WV, Mattozz C, Melis L, De Gado F, et  al. Hydrofiber dressing and wound repair: review of the literature and new patents. Recent Patents Inflamm Allergy Drug Discov. 2011;5(2):150–4. 25. Dinah F, Adhikari A. Gauze packing of open surgical wounds: empirical or evidence-based practice? Ann R Coll Surg Engl. 2006;88:33–6. 26. Jones V, Grey JE, Harding KG.  Wound dressings. BMJ. 2006;332:777–80. 27. Giudice G, Filoni A, Maggio G, Bonamonte D, Vestita M, et al. Cost analysis of a novel enzymatic debriding agent for management of burn wounds. Biomed Res Int. 2017;2017:9567498. 28. Kern MA, Depka N, Schackert C, Henkel W, Hirche CR.  Enzymatic burn wound debridement with NexoBrid1: cost simulations and investigations on cost efficiency. Gesundheitsökonomie und Qualitätsmanagement. 2018;23:21–8. 29. Russo R, Carrizzo A, Barbato A, Rasile BR, Pentangelo P, Ceccaroni A, Marra C, Alfano C, Losco L.  Clinical evaluation of the efficacy and tolerability of Rigenase® and polyhexanide (Fitostimoline® Plus) vs. hyaluronic acid and silver sulfadiazine (Connettivina® Bio Plus) for the treatment of acute skin wounds: a randomized trial. J Clin Med. 2022;11(9):2518. 30. Hoogewerf CJ, Hop MJ, Nieuwenhuis MK, Oen IM, Middelkoop E, Van Baar ME.  Topical treatment for facial burns. Cochrane Database Syst Rev. 2020;7(7):CD008058. 31. Hirsch T, Ashkar W, Schumacher O, Steinstraesser L, Ingianni G, Cedidi CC. Moist exposed burn ointment (MEBO) in partial thickness burns—a randomized, comparative open mono-center study on the efficacy of dermaheal (MEBO) ointment on thermal 2nd degree burns compared to conventional therapy. Eur J Med Res. 2008;13(11):505–10. PMID: 19073386. 32. Isak V, Beerli T, Cozzio A, Flatz L.  A rare case of localized argyria on the face. Case Rep Dermatol. 2019;11(1):23–7. 33. Fernandez R, Green HL, Griffiths R, Atkinson RA, Ellwood LJ.  Water for wound cleansing. Cochrane Database Syst Rev. 2022;9(9):CD003861. 34. Cooper DD, Seupaul RA. Is water effective for wound cleansing? Ann Emerg Med. 2012;60:626–7.

10  Dressing in Burns 35. Ryssel H, Kloeters O, Germann G, Schäfer T, Wiedemann G, Oehlbauer M. The antimicrobial effect of acetic acid - an alternative to common local antiseptics? Burns. 2009;35:695–700. 36. Miller LM, Loder JS, Hansbrough JF, Peterson HD, Monafo WW, Jordan MH. Patient tolerance of topical chlorhexidine diphosphanilate: a new topical agent for burns. Burns. 1990;16:217–20. 37. Moriarty R.  Corrosive chemicals: acids and alkali. Drug Ther. 1979;1:3.

111 38. Leonard LG, Scheulen JJ, Munster AM.  Chemical burns: effect of prompt first aid. J Trauma. 1982;22(5):420–3. 39. Yano K, Hata Y, Matsuka K, et al. Effects of washing with a neutralizing agent on alkaline skin injuries in an experimental model. Burns. 1994;20(1):36–9. 40. Palao R, Monge I, Ruiz M, et  al. Chemical burns: pathophysiology and treatment. Burns. 2010;36(3):295–304. 41. Kuckelkorn R, Schrage N, Keller G, et al. Emergency treatment of chemical and thermal eye burns. Acta Ophthalmol Scand. 2002;80(1):4–10.

Innovative Dressings


Evelin Makuc

As the modern world’s population has become an increasingly aging one, chronic conditions including skin healing disorders have become more and more common, bringing about a huge economic and sanitary burden. Statistics report that, among chronic limb wounds, for example, diabetic foot ulcers are the most common, being responsible for up to 70% of lower limb amputations, and, as a consequence, for increased mortality [1]. This and other significant reasons, which include psychological and social implications of having to deal with poorly healing lesions, have led to the need to develop smart materials that can optimize the management of said conditions. Progression in knowledge of wound etiology and healing processes has led to the introduction of more technological, advanced dressing materials that target specific aspects of the wound, thus optimizing the healing process. While traditional dressings are still widely used both for their low cost and simple manufacturing process, these are, however, considered inert dressings, because of the lack of interaction with the wound bed, and inability to create the optimal conditions for an accelerated healing process, unlike advanced dressings [2].

Nowadays, dressings are considered optimal and efficient when they are both cost-effective and deliver specific beneficial effects. These include antibacterial properties, pain relief, epithelialization acceleration, mechanical protection and flexibility, exudate absorption, and dissolving of necrotic tissue and fibrin [3]. Innovative dressings, besides providing better biocompatibility, moisture retention, and degradability [4], nowadays provide innovative technology with the use of nanotechnology, micelle matrixes, and antimicrobial agents. They not only function as a protective layer, but also operate as diagnostic sensors in wound monitoring and wound healing promotion. Wound care dressings can be summarized into three macro-groups: passive, interactive, and bioactive products [5]. While passive dressings are suitable for dry wounds and not for moderately to highly exuding ones, interactive and bioactive ones perform brilliantly: the first by creating an hypoxic environment that has proven to be highly stimulating re-epithelialization and granulation [6], the second, by delivering bioactive compounds to the wound bed. More in detail, dressings can be further divided into four categories, according to the Italian Association of Chronic Wounds position paper of 2014: [7].

E. Makuc (*) RN and Wound Care Expert at Cattinara Hospital, ASUGI, Trieste, Italy e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



• Autolysis and debridement promoting dressings. • Granulation-stimulating dressings. • Antimicrobial dressings. • Re-epithelialization promoting dressings.

E. Makuc

62.5% of slough [12], resulting in an effective, safe dressing in the management of wounds regardless of their level of exudate or healing stage, with superior capacity when compared to commonly used hydrofibers [13]. This technology can be applied and combined Some innovative dressing technologies are with different materials, or can be preceded by listed as follows and will be thoroughly analyzed preparation treatments with dressings containing in this chapter: polyacrylate and hydro-desloughing fibers (as in UrgoClean Ag dressing), which are highly absor• TLC-NOSF Technology-based dressings. bent and trap slough, bacteria, and biofilm resi• Gelling hydrofiber dressings. dues, keeping the wound deterged. Biofilm is a • Microbe-trapping dressings. structured colony of bacteria enclosed in a polysaccharide extracellular matrix that takes only 2 to 4 days to form and is present in over 80% of 11.1 TLC-NOSF Technology-Based infections [14, 15], hindering healing by promotDressings ing inflammation, exudate production, and slough; it also acts as barrier against antimicroTechnology lipidocolloid with nano-oligo-­ bial molecules, antibodies, and macrophages saccharide factor (TCL-NOSF) is a lipidocolloid [16]. matrix containing sucrose octasulfate potassium Most silver-based dressings have the ion salt: This salt has proven to actively inhibit matrix impregnated into the absorbent fibers or foam, metalloproteases (MMPs) and to interact with whereas the silver contained in some advanced different growth factors. Lipidocolloid dressings like UrgoClean Ag® comes directly in Technology-silver matrix (TLC-Ag)-based dress- contact with the wound bed because of its incorings have been in use since 2006, supported by poration in the lipidocolloid layer, maximizing high-quality medical evidence, for the manage- its antimicrobial efficacy [11]. ment of wounds at high risk or with ongoing Change in these types of dressings may vary infection [8]. This technology can be applied to according to the clinical conditions and the exucontact layers, adhesive and non-adhesive foams, date level of the wound, approximately every and gelifying fibers and has lately been used as other day. coating of polyacrylate polyabsorbent fibers. They are mostly indicated for acute and Results from a randomized controlled trial on chronic lesions with and without local infection chronic leg ulcer treatment [9] and an observa- and are contraindicated in patients with allergies tional study on 227 patients [10] suggest an to any of the components. increased efficacy of wound healing and reducAnother type of polyabsorbent fiber dressing tion in complications following the use of silver-­ containing a protease inhibitor (TLC-NOSF healbased dressings, as opposed to dressings without ing matrix that inhibits excess metalloproteinase) silver: TCL-Ag technology has a broad-spectrum and polyabsorbent fibers that bind, trap, and antimicrobial effect along with anti-biofilm retain exudate is UrgoStart Plus®. This is particuaction thanks to the synergic if not enhanced larly indicated for diabetic foot ulcers: Lower action of the matrix and the polyabsorbent fibers limb wounds, diabetic foot, and pressure wounds that mechanically break down biofilm of also generally require an average of 210 days to heal methicillin-resistant Staphylococcus aureus completely [17, 18]. (MRSA) and pseudomonas aeruginosa, remainAlong with the underlying causes, three other ing active for up to 7 days [11]. factors greatly affect the healing: process: excess Furthermore, it reduces up to 32.5% of the MMP damages the extracellular matrix and is wound surface after a 4-week treatment and up to systematically higher in chronic wounds as

11  Innovative Dressings

opposed to acute ones [19]. Vascular alterations limit oxygen supply [20] and slough recurrence perpetuates inflammation. When addressing these issues, physicians must prioritize quality of life, avoidance of further complications, and reduction of healthcare costs. That being stated, innovative dressings such as UrgoStart Plus® have proven to reduce that median healing time by 100 days on average [21] thanks to its polyabsorbent fibers that absorb excess exudate and bind slough and debris through electrostatic mechanism and thanks to its TCL-NOSF matrix technology (Lipidocolloid Technology-Nano-Oligosaccharide Factor). This patented matrix technology, once in contact with the wound bed, hydrates and turns into a gel that creates a favorable healing environment by inhibiting excess matrix metalloproteinase (MMP) and by promoting angiogenesis through endothelial cell migration. These properties combined make the dressing highly cohesive and provide atraumatic, painless removal [22, 23]. Following adequate treatment of the underlying causes (compression, revascularization, etc.), advanced dressing must be changed every other day at the beginning of treatment and subsequently every 7 days considering the level of exudate and clinical conditions of the wound. If infection of the wound bed coexists, it is recommended to first apply a silver-based dressing (such as UrgoClean Ag®) before starting a TLC-based treatment. In light of new scientific evidence proving that TLC-NOSF technology reduces healing time of diabetic foot ulcers by approximately 60  days and heals 60% more patients affected by DFU compared to wounds treated with non-interactive dressings [24], 2019 International Working Group on the Diabetic Foot (IWGDF) guidelines and NICE [25] strongly recommend the use of TLC-NOSF based dressings like UrgoStart for local treatment of neuro-ischemic diabetic foot wounds [26]. It is mainly indicated on lower limb lesions, diabetic foot lesions, and pressure wounds, while contraindications include heavy


bleeding wounds, cancerous wounds, and abscesses. Polyester fibers like those used for UrgoStart Contact® dressing are also efficiently combined with lipidocolloidal matrix rich in saccharide factors (TLC-NOSF Technology), which creates a humid environment that stimulates tissue regeneration, inhibits metalloprotease, excess and promotes neoangiogenesis [27]. This polyester weave allows exudate to be transferred to the secondary dressing, preventing internal growth of granulation tissue, while the composition of the fibers does not leave dressing fragments that could have pro-inflammatory properties. Because of its flexibility and atraumatic painless removal, UrgoStart is indicated in the treatment of cavitated, hardly accessible, or deep wounds. Ideal dressing change may vary from 2 to 7 days according to healing stage and level of exudate, for a total recommended treatment time of at least 8 weeks. Contraindications to the use of this type of dressing include tumor lesions, fistulas, and abscess.

11.2 Hydroactive Dressings, Gelling Fiber Dressings, and 3D FIT Technology Dressings Hydroactive dressings are multilayered, highly absorbent polymer dressings. Some even have a waterproof outer layer, and although hydroactive dressings are similar to foams, they have a different action for absorbing exudate because they draw fluid into the structure of the polymer and trap the exudate to maintain a moist environment, whereas foams absorb exudate by a siphon effect. The main advantages of the hydroactive dressing are that they (1) absorb exudate quickly and effectively, reducing the risk of maceration, and they provide moisture to dry wounds, facilitating faster healing; they do not stick to the wound bed, making removal atraumatic for the patient; they also soothe painful wounds, providing greater


patient comfort and tolerability, and finally ­protect the wound from bacteria, reducing the risk of infection. Hydroactive dressings are indicated for highly exuding wound surface and cavity wounds, including pressure injuries, venous leg ulcers, and minor burns. Due to the ability to contract and expand without causing constriction, they are particularly useful over joints. Because of their absorbing abilities, these dressings are not indicated for lightly exuding and dry wounds [28]. Gelling fiber dressings are absorbent wound dressings that contain synthetic fibers made from sodium carboxymethyl cellulose, strengthening cellulose fibers, and other absorbent materials. As wound fluid is absorbed into the dressing, a gel forms, which assists in maintaining a moist environment for optimal wound healing and the formation of granulation tissue. Biatain Fiber® with HexaLock technology is an example of a new gelling fiber in the form of rope or sheet dressing with characteristic heat-­ sealed hexagonal unities that block exudate and maintain their original shape thanks to the innovative HexaLock technology [29]. This new dressing can be applied to exuding wounds, especially undermined and cavitary wounds, with the advantage of creating a stronger, quicker gelling substance when in contact with the wound bed, as well as better managing the exudate level through absorption, retention, and resistance to shrinkage, when compared with traditional alginate dressings [30]. Like other gelling fibers, Biatain Fiber® can also be combined with other super-absorbent dressings, which, however, must conform to the wound edges: Contact with exuding wound bed creates a cohesive gel through vertical absorption, which prevents the surrounding skin from macerating. In addition to its absorbing properties, Biatain fiber greatly supports autolytic debridement and de-sloughing, promoting faster wound healing [29]. 3D FIT technology dressings include dressings with the ability to perfectly adapt and conform to the wound bed: These can consist of multilayer, polyurethane adhesive, and non-­

E. Makuc

adhesive absorbent foams (e.g., Biatain Ag®) with continuously released silver ions that provide antimicrobial properties up to 7 days. The non-adhesive area is in direct contact with the wound bed, while the external hydrophobic sheath protects from external agents. Thanks to its patented 3D FIT technology, the dressing absorbs all excess exudate, when in contact with the wound bed, and molds itself to the wound bed’s shape for up to 2 cm of depth. The adhesive border is delicate on the surrounding skin and allows atraumatic removal, leaving no residues. Indicated on acute and chronic wounds with high bacterial presence, with medium to high exudation level. The dressing can also have prophylactic use, and dressing change can occur in 5 to 7 days. Contraindications: Silver Hypersensitivity [31].

11.3 Dressings with Hydrofiber and More Than Silver Technology “Hydrofiber” and “more than silver” technology dressings are antimicrobial absorbent dressings developed to counteract biofilm on the wound bed. To accelerate healing, biofilm and excess exudate must be managed. By placing the dressing on the wound bed, hydrofiber technology begins to absorb the exudate and form a cohesive gel ensuring full contact with the wound bed. “Hydrofiber” technology is composed of carboxyl methyl cellulose fibers and physically removes and pulls debris and bacteria away from the wound by trapping them inside the dressing. The “more than silver” technology consists of three components: BEC, EDTA, and Ag+ that act synergistically to disrupt and destroy biofilm. Benzethonium chloride (BEC) is a surfactant that reduces surface tension within the biofilm and its action helps antibiofilm agents reach bacteria more effectively and faster. Ethylenediaminetetraacetic acid or disodium salt (EDTA) is a metal chelating agent that selectively binds and removes metal ions that hold the

11  Innovative Dressings

EPS matrix of the biofilm together, exposing the microorganisms within it. Ag+ − Once defenses are down, the ionic silver can reach and kill exposed microorganisms. The concentration of silver is 1.2%, and the dressing provides safe, broad-spectrum antimicrobial action. Silver ions become available only when the dressing gels, and this modulated action ensures a constant silver level to destroy and prevent biofilm reproduction. Strengthening the fibers of the dressing allows for increased tensile strength and safe removal in a compact manner without leaving residue [32–40].


ily irrigated from the wound at dressing change using normal dressing change solutions. Contraindications include use on third- and fourth-degree burns.

11.3.2 PluroGel® Burn and Wound Dressing with PSSD It consists of a comfortable gel containing PluroGel surfactant concentrate with the addition of antimicrobial silver sulfadiazine: can manage the same lesions listed for PluroGel Burn; however, should not be used in case of known sensitivity to sulfadiazine, silver, or sulfonamides.

11.3.1 PluroGel® Burn and Wound Dressing

11.3.3 Issue-Targeting Dressings

This is a 100% water-soluble, biocompatible surfactant gel utilizing micelle matrix technology. This dressing as well comes with or without silver ions and shows autolytic and pro-healing properties. Slough, bacteria, and debris are effectively trapped and softened by the concentrated surfactant that also helps maintain an optimal moist environment. Its painless removal increases patient compliance, while the unique micelle matrix allows the dressing to maintain thickness [41]. PluroGel® Burn and Wound Dressing are indicated for use on chronic vascular ulcers, venous ulcers, diabetic ulcers, draining wounds, partialand full-thickness wounds, pressure injuries, second-degree burns, surgical wounds, trauma wounds (abrasions, lacerations, skin tears), and tunneling/undermining wounds. It can be applied directly onto secondary dressing using a sterile applicator (foam for a shallow wound, packing strips for a deeper wound). Thickness of 3 mm (slightly more than nickel) is ideal for minimal drainage and 5 mm (2 nickels thick) for moderate drainage or dressing change every 3 days. Where applicable, the gel can be covered with absorbent dressing and kept for up to 3  days: PluroGel® is 100% water-soluble and can be eas-

Innovative dressings have been developed for the treatment and management of specific skin issues. One of these issues is Intertrigo. Intertrigo is a form of moisture-associated skin damage and is commonly found in skin-fold areas such as armpits, under the breasts, abdomen, toes, and groin. It occurs as a result of prolonged exposure to perspiration and skin-to-skin contact. Obese individuals are at higher risk of developing intertrigo, and it is exacerbated by factors such as immobility and poor hygiene. Patients may experience itching, and burning sensation, often combined with unpleasant odor, with great affection of quality of life and risk of secondary infection [42]. InterDry® is a product for the management of skin-fold complicated conditions, such as Intertrigo, which targets all three factors associated with skin-fold damage simultaneously: skin moisture, friction, and microbial proliferation, thanks to its antimicrobial silver complex. The fabric can be shaped and applied in a single layer after assessing and drying the affected area, making sure to leave at least 5 cm of excess fabric to be exposed outside the skin fold to promote evaporation. Each application must not exceed 5  days, after which the fabric must be replaced with a new one.

E. Makuc


InterDry has been demonstrated to provide relief and reduction in symptoms such as erythema, denudement, maceration, itching, and pain within 5 days from application [43, 44].

11.3.4 Activated Carbon-Based Dressings Zorflex® wound contact dressings accelerate the wound healing process 1 [45–47] across a diverse range of wound types. Activated carbon cloth (ACC) has been used for many years as an anti-­ odor component in wound dressings. The key innovation behind Zorflex® activated carbon cloth is the recent discovery that, when in direct contact with the wound bed, helps significantly accelerate wound healing  – attracting and trapping the microbes from the wound bed into the activated carbon cloth through electrostatic force. It has proven effective against MRSA and as a protease modulator [47], providing an effective antimicrobial barrier for up to 7 days. Besides reducing pain and exudate, it reduces and controls odor through its highly absorbent properties. This dressing is indicated for full- and partial-­ thickness wounds such as traumatic wounds, surgical sites, fumigating carcinomas, pressure ulcers, venous leg ulcers, diabetic foot ulcers, and recipient graft sites.

11.4 Copper Antimicrobial Dressings Dressings impregnated with copper oxide microparticles are indicated for acute, post-surgical, and chronic wounds such as • • • • •

Diabetic wounds. Lower extremity ulcers. Pressure injuries. Superficial epidermal and dermal burns. Surgical wounds.

Copper is an essential nutrient mineral with potent broad-spectrum antimicrobial efficacy; it

is safe, biocompatible, nonsensitizing, and non-­ irritating to the skin. The dressings are disposable with an inner absorbent layer and one or two outer nonwoven, nonadherent layers. All layers are impregnated with copper oxide particles and can be left in place for up to 7 days.

11.4.1 Dialkylcarbamoyl Chloride (DACC) Technology Dialkylcarbamoyl chloride (DACC) is a synthetic fatty acid that is highly hydrophobic: Since most microorganisms responsible for chronic wounds have hydrophobic surfaces, in vitro data suggest that bacteria and endotoxins naturally bind irreversibly to the unique DACC-coated dressing and, therefore, unlike other dressings that kill bacteria and the microbes, when these dressings are removed, a great quantity of bacteria and microbes is also removed [48]. This technology can be applied to different materials, coating diverse types of dressings according to the kind of wound and main issue to address. Cutimed Siltec Sorbact®, for example, consists of a super-absorbent foam with a silicone part that comes in contact with the wound bed, while the top part is made of a highly breathable film. This dressing is designed to greatly manage exudate but also traps bacteria and maintains wound moisture. It can be used for all shallow, contaminated, and colonized or infected wounds with moderate to high exudate level (traumatic wounds, chronic leg ulcers, diabetic and pressure wounds, and fungal infections). Bacteria-binding properties may be altered if used in combination with creams and ointments, so these are generally not recommended when using Cutimed Siltec Sorbact. Cutimed Sorbact dressing pad, instead, is an exudate absorbing and bacteria-binding dressing that is coated with DACC technology. It best works in a moist environment and can be used for all traumatic and nontraumatic chronic wounds with low levels of exudate. As with Cutimed Siltec Sorbact, ointments and creams are not recommended in

11  Innovative Dressings

c­ombination with this dressing to not alter its bacteria-binding properties. Gels and hydrogels, like Cutimed Sorbact Gel®, can be also used for the management of low levels of exudate and to bind bacteria in sloughy wounds. Combination with hydropolymer gel sheets for Cutimed Sorbact Hydroactive® is designed to reduce wound bioburden, as well as absorb and lock in exudate while maintaining a moist environment. Moreover, its non-adhesive borders make its removal atraumatic for the patient.


the regulation of immune responses and proper course of inflammation. The medicament promotes re-epithelialization by controlling the proliferation of keratinocytes along the wound margins already in the inflammatory phase, which will then serve to re-­ epithelialize the granulation tissue in preparation.


1. Lindholm C, Searle R.  Wound management for the 21st century: combining effectiveness and efficiency. Int Wound J. 2016;13:5. 11.5 Primary Wound Dressing 2. Broughton G II, Janis J, Attinger CE. A brief history of Spray wound care. Plast Reconstr Surg. 2006;117:6S–11S. 3. Mirhaj M, Labbaf S, Tavakoli M, Seifalian Medicament based on natural extracts derived AM. Emerging treatment strategies in wound care. Int from two plants, Hypericum perforatum or St. Wound J. 2022;19(7):1934. John’s Wort and Azadirachta indica, A.  Juss or 4. Hopper GP, Deakin AH, Crane EO, Clarke J.  Enhancing patient recovery following lower limb Neem tree that are found to have anti-­ arthroplasty with a modern wound dressing: a prospecinflammatory, healing, antibacterial properties tive, comparative audit. J Wound Care. 2012;21:200– against Gram-negative and Gram-positive micro3. organisms as well as biocidal and repellent effects 5. Ochoa M, Rahimi R, Zhou J, Jiang H, Yoon CK, Maddipatla D, Narakathu BB, Jain V, Oscai MM, against harmful dipterans. Morken TJ, Oliveira RH, Campana GL, Cummings The commercial product 1—Primary wound OW, Zieger MA, Sood R, Atashbar MZ, Ziaie dressing (1PWD®) derived from the ENEA patB.  Integrated sensing and delivery of oxygen for ent is a plant-based, non-single-molecule, truly next-generation smart wound dressings. Microsyst Nanoeng. 2020;6:46. effective (evidence-based) preparation with “all-­ 6. Hong WX, Hu MS, Esquivel M, Liang GY, Rennert in-­ one” characteristics as primary dressing, RC, McArdle A, Paik KJ, Duscher D, Gurtner GC, applicable at any stage of the wound, i.e., from Lorenz HP.  The role of hypoxia-inducible factor in the moment of injury and until complete healing, wound healing. Adv Wound Care (New Rochelle). 2014;3:390. which allows the resolution of all wounds both 7. Greco A, Mastronicola D, Magnoni C.  Functional acute and chronic, unlike the countless treatment classification of wound dressings. AIUC posiprotocols, which involve the simultaneous or suction document on wound dressing. Acta Vulnol. cessive use of different products. 2014;12(3):143–52. 8. Dissemond J, Lützkendorf S.  Clinical evaluaThe medicament exerts a powerful attractive tion of polyabsorbent TLC-NOSF dressings on ability to macrophages responsible for infection chronic wounds: a prospective, observational, mulcontrol in the wound bed, which disappear during ticentre study of 1140 patients. J Wound Care. the granulation phase. The initial phase of the 2020;29(6):350–61. 9. Lazareth I, Meaume S, Sigal-Grinberg ML, et  al. scarring process is dominated by the inflammaEfficacy of a silver lipidocolloid dressing on heavtory phase, which is characterized by local actiily colonised wounds: a republished RCT.  J Wound vation of the innate immune system, resulting in Care. 2012;21(2):96–102. an immediate influx of polymorphonuclear leujowc.2012.21.2.96. kocytes (neutrophils) followed by subsequent 10. Dissemond J, Dietlein M. Use of a TLC-Ag dressing on 2270 patients with wounds at risk or with signs of invasion of blood monocytes that differentiate local infection: an observational study. J Wound Care. into tissue macrophages, which are essential for 2020;29(3):162.

120 11. Desroche N. et  al. Characterization of the antimicrobial spectrum and anti-biofilm activity of a new silver-containing dressing with poly-absorbent fibres and antimicrobial silver matrix. Poster EWMA. 2016. 12. Dalac S, Sigal L.  Clinical evaluation of a dressing of dressing with poly-absorbent fibres and a silver matrix for managing chronic at risk of infection: a non comparative trial. J Wound Care. 2016;25(9):531. 13. Meaume S, Dissemond J, Addala A, et al. Evaluation of two fibrous wound dressings for the management of leg ulcers: results of a European randomised controlled trial (EARTH RCT). J Wound Care. 2014;23(3):105–16. jowc.2014.23.3.105. 14. Schierle CF, De la Garza M, Mustoe TA, et  al. Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model. Wound Repair Regen. 2009;17:354–9. 15. Zhao G, Hochwalt PC, Usui ML, et  al. Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: a model for the study of chronic wounds. Wound Repair Regen. 2010;18:467–77. 16. Wolcott RD, Rhoads DD, Dowd SE.  Biofilms and chronic wound inflammation. J Wound Care. 2008;17(8):333–41. 17. Relazione al ministro incaricato della sicurezza sociale e al Parlamento sull’evoluzione delle tasse e delle entrate dell’assicurazione sanitaria per il 2014. Luglio 2013. Banca dati del Fondo nazionale di assicurazione malattia (CNAM): lesioni degli arti inferiori: 210 giorni; lesioni da pressione: 223 giorni; lesioni del piede diabetico: dati comparativi non disponibili2. 18. Herber OR, Schnepp W, Rieger MA.  A systematic review on the impact of leg ulceration on patients’quality of life. Health Qual Life Outcomes. 2007;5:44. 19. Lazaro JL, Izzo V, Meaume S, Davies AH, Rm L, Uccioli L.  Elevated levels or matrix metalloproteinases and chronic wound healing: an updated review of clinical evidence. J Wound Care. 2016;25(5):277–87. 20. Honnegowda TM, Kumar P, Udupa EG, Kumar S, Kumar U, Rao P.  Role of angiogenesis and angiogenic factors in acute and chronic wound healing. Plast Aesthet Res. 2015;2:243–9. 21. Münter KC, Meaume S, Augustin M, Senet P, Kérihuel JC.  The reality of routine practice: a pooled data analysis on chronic wounds treated with TLC-NOSF wound dressings. J Wound Care. 2017;26(Sup2):S4– S15; Erratum in: J Wound Care. 2017 Mar 2; 26(3). 22. Pernot JM, et al. Interactions between poly-absorbent fibres and fibrin. Poster Journées Cicatrisations; 2017. 23. Meaume, et  al. The importance of pain reduction through dressing selection in routine wound management: the MAPP study. J Wound Care. 2004;13(10):409–13. 24. EXPLORER STUDY. 25. NICE.  UrgoStart for treating diabetic foot ulcers and leg ulcers. MTG42.

E. Makuc 26. h t t p s : / / i w g d f g u i d e l i n e s . o r g / w p -­c o n t e n t / uploads/2019/05/06-­I WGDF-­r ecommendations-­ wound-­healing-­2019.pdf/. 27. Edmonds M, Lázaro-Martínez JL, Alfayate-García JM, Martini J, Petit JM, Rayman G, Lobmann R, Uccioli L, Sauvadet A, Bohbot S, Kerihuel JC, Piaggesi A. Sucrose octasulfate dressing versus control dressing in patients with neuroischaemic diabetic foot ulcers (Explorer): an international, multicentre, double-blind, randomised, controlled trial. Lancet Diabetes Endocrinol. 2018;6(3):186–96. 28. Weller CD, Team V, Sussman G. First-line interactive wound dressing update: a comprehensive review of the evidence. Front Pharmacol. 2020;11:155. https://; PMID: 32180720; PMCID: PMC7059819. 29. von Hallern B, M Berg, M Hintner, C Hartleben. First clinical evaluation of a new gelling fiber dressing Biatain® fiber. 30. Larsen TRO et al. Wounds UK. 2019. 31. Andrea Bellingeri—Prontuario del wound care. 32. Donlan RM, Costerton JW. Bio-films: survival mechanisms of clinically relevant microorganisms. Clin Micro Rev. 2002;15:167–93. 33. Malone M, et al. The prevalence of biofilm in chronic wounds: a systematic review and meta-analysis of published data. J Wound Care. 2017;1:20–5. 34. Wolcott R, Sanford N, Gabrilska R, et al. Microbiota is a primary cause of pathogenesis of chronic wounds. J Wound Care. 2016;25(10):S33–43. 35. Hall-Stoodley LI, et al. Towards diagnostic guidelines for biofilm-associated infection. FEMS Immunol Med Microbiol. 2012;65:127–45. 36. Wolcott RD, et  al. Biofilm maturity studies indicate sharp debridement opens a time dependent therapeutic window. J Wound Care. 2010;19:320–8. 37. Flemming H, Wingender J.  The biofilm matrix. Nat Rev. 2010;8:623–33. 38. Donlan R. Biofilms: microbial life on surface. Emerg Infect Dis. 2002;8:881–90. 39. Gurjala AN, et  al. Development of a novel, highly quantitative in vivo model for the study of bio-film-­ impaired cutaneous wound healing. Wound Rep Reg. 2011;19:400–10. 40. Costerton JW, Stewart PS, Greenberg EP.  Bacterial bio-films: a common cause of persistent infections. Science. 1999;284:1318; TM Trademark of Convatec Inc. 2020. 41. Ratliff CR.  Management of a groin wound using a concentrated surfactant-based gel dressing. J Wound Ostomy Cont Nurs. 2018;45(5):465–7. 42. Janniger CK, Schwartz RA, Szepietowski JC, Reich A. Intertrigo and common secondary skin infections. Am Fam Physician. 2005;72(5):833–8. 43. Metin A, et  al. Recurrent candidal intertrigo: challenges and solutions. Clin Cosmet Investig Dermatol. 2018;11:175–85. 44. Kennedy-Evans KL, Viggiano B, Henn T, Smith D.  Multi-site feasibility study using a new textile with silver for management of skin conditions

11  Innovative Dressings located in skin folds. Poster presented at:20th Annual Symposium on Advanced Wound Care; 2007; Tampa, FL and 39th WOCN® Society Annual Conference; 2007; Salt Lake City, UT. 45. Scheer HS, Kaiser M, Zingg U.  Results of directly applied activated carbon cloth in chronic wounds: a preliminary study. J Wound Care. 2017;26(8):476. 46. Miller MS, Markey L, Yoder R.  Use of a unique carbon-­based textile dressing zorflex to promote healing and prevent amputation. WOW 2017 poster.

121 47. Murphy N.  Reducing infection in chronic leg ulcers with an activated carbon cloth dressing. Br J Nurs. 2016;25:12. 48. Totty JP, Bua N, Smith GE, Harwood AE, Carradice D, Wallace T, Chetter IC. Dialkylcarbamoyl chloride (DACC)-coated dressings in the management and prevention of wound infection: a systematic review. J Wound Care. 2017;26(3):107–14. https://doi. org/10.12968/jowc.2017.26.3.107.

Compression Therapy in Ulcer Care


Giovanni Mosti

12.1 Introduction Leg ulcers are very often due to superficial or deep venous disease (both because of venous obstruction or insufficiency) [1–4]. Ambulatory venous hypertension, the hemodynamic result of the venous disease, is the key pathophysiologic mechanism, leading to skin damage and finally venous ulcers, through several but not completely understood mechanisms. Fibrin cuff formation around the microvessels, impairing gases (O2, CO2) exchange [5], white cells entrapment [6] causing skin necrosis, and growth factor inhibition [7] producing a stagnation of the healing process, have been considered as the ultimate pathophysiologic mechanisms in venous leg ulcer (VLU) formation and maintenance, due to blood stasis in the lower leg. The VLU treatment must be based on the correction of the venous hemodynamic impairment, leading to VLU through a cascading mechanism. Fixing venous hemodynamics can be achieved by means of invasive procedures (open surgery, endovascular procedures such as endovenous laser ablation, radiofrequency, foam sclerotherapy, and conservative hemodynamic treatment) but also conservatively by compression therapy (CT), walking, and leg elevation.

G. Mosti (*) Angiology Department, Clinica MD Barbantini, Lucca, Italy

In this chapter, updated information about CT effects will be provided, not only on venous hemodynamics. The whole set of CT effects results in the high effectiveness of CT in significantly increasing the VLU healing rate. In addition, they are of utmost importance in achieving a high healing rate also in leg ulcer with different pathophysiology.

12.1.1 Evidence-Based Compression Therapy Compression therapy is considered the cornerstone of VLU treatment and is recommended in all national and international guidelines on VLU treatment. Furthermore, it is the only therapeutical procedure that achieved the level of evidence 1A in many guidelines [8, 9]. No other ulcer treatment achieved the same level of evidence. Compression therapy can be applied with different compression materials and devices. The crucial point is choosing the most effective compression modality, which is still matter of debate.

12.1.2 Elastic and Inelastic Materials All available compression devices (elastic and inelastic bandages, elastic stockings, adjustable compression wraps, and hybrid pumps) are basi-

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



G. Mosti

cally made up of elastic or inelastic material. When wrapped on the leg, they exert a compression pressure, which, according to the Laplace law, depends on the stretch applied to the compression material, the number of turns of compression material, and the radius of the leg segment [10]. Elastic and inelastic materials have completely different physical characteristics. Elastic or long-stretch material (represented by elastic stockings or elastic bandages with an extensibility higher than 100%) gives way to muscle expansion, which occurs during standing and physical activity. This results in a very low Static Stiffness Index (SSI) [11, 12], the difference between the standing and the supine pres-

sure, which represents the most important indicator of elasticity/inelasticity of compression devices. The SSI is 70–80 mmHg during standing. The SSI is always >10, which characterizes the inelastic range. The strong or very strong pressure peaks during muscular exercise will overcome the intravenous pressure, intermittently occluding the vein and so restoring a kind of valve mechanism [14] (Fig. 12.5).

In a few words, the inelastic material is able to adapt to the body position by exerting a relatively low pressure in the resting position (comfortable) and a strong or very strong pressure in standing position and during muscle activity (effective) coming close to an ideal compression device [15]. Unfortunately, the multilayer, multicomponent inelastic bandages are difficult to apply and require expert and well-educated personnel. In a series of papers, it was demonstrated that only 10 to 60% (depending on the paper) of expert health personnel treating venous ulcers were able to

12  Compression Therapy in Ulcer Care


Fig. 12.4  Compression pressure recording of an inelastic bandage exerting a supine pressure of 60  mmHg. Compression pressure increase by dorsiflexions, standing up, and walking is very high: intermittent compression with high-pressure peaks able to overcome the intravenous pressure (red line) restoring a kind of valve mechanism. Small ellipses represent veins always narrowed/ occluded by strongly stretched elastic bandages. DSI:

Dynamic Stiffness Index is the difference between diastolic pressure and systolic pressure performing foot dorsiflexions in supine position; SSI: Static Stiffness Index is the difference between standing and supine positions. WPA: Walking pressure amplitude is the difference between systolic pressure and diastolic pressure while walking

apply the target pressure with different inelastic bandages [16–20].

promoting a higher healing rate of VLU, which is due to the venous hemodynamic impairment. In addition, we have pieces of evidence that the higher the compression pressure the higher the healing rate [25–27] and this is clearly in favor of inelastic bandages effective in exerting a much higher standing pressure compared with elastic materials. Amazingly, we have many papers claiming a greater effectiveness of elastic stockings or bandages compared with inelastic material [28–41]. Unfortunately, studies comparing elastic and inelastic devices have so many flaws that their conclusions are hard to believe [42].

12.1.3 Which Compression Material for Ulcer Treatment? Solid data in favor of elastic or inelastic material as the best choice to optimize VLU healing did not exist at the being time. There are clear pieces of evidence that inelastic is more effective than elastic material in counteracting venous hemodynamic impairment [14, 21–24]. This “should ensure” a greater effectiveness in


G. Mosti

Fig. 12.5  Compression pressure recording of an inelastic bandage exerting a reduced supine pressure of 40 mmHg. Compression pressure increase by dorsiflexions, standing up, and walking is still very high: intermittent compression with high-pressure peaks is still able to overcome the intravenous pressure (red line) again restoring a kind of valve mechanism. Please notice the difference in pressure behavior of the elastic material applied with the same resting pressure in Fig. 12.2. The succession of small circles

and ellipses represent veins narrowing/occluding at every muscle contraction during physical exercise. DSI: Dynamic Stiffness Index is the difference between diastolic pressure and systolic pressure performing foot dorsiflexions in supine position; SSI: Static Stiffness Index is the difference between standing and supine positions. WPA: Walking pressure amplitude is the difference between systolic pressure and diastolic pressure while walking

12.1.4 Comparing Compression Materials

turing company. Unfortunately, we cannot know the bandage pressure that can be extremely variable [45, 46] as it only depends on the stretch applied to the bandage, layers overlap, radius of different parts of the leg and, as a matter of fact, on the health personnel skillness that is usually poor [16–20]. As a consequence, not measuring the compression pressure, it is impossible to know if the bandages were correctly applied. They could have been applied too stretched, becoming painful and dangerous or, much more frequently, too loose, becoming ineffective [16]. In addition, not measuring the pressure and cal-

In almost all trials comparing different compression devices, the exerted pressure was almost never measured despite it represents the dosage of compression, the most important parameter concerning CT, and even if compression pressure measurement is easy to perform with accurate and cheap devices [43, 44]. When compression pressure is not measured, we approximately know the elastic stocking pressure because it is declared by the manufac-

12  Compression Therapy in Ulcer Care

culating the SSI, an amazing mistake in almost all studies comparing elastic and inelastic bandages was made. In these studies [28–35], the prototype of elastic material is the so-called four-layer bandage, which was considered elastic by definition as it is made up of four different elastic components. Nevertheless, by measuring supine and standing pressure and calculating the SSI of the final bandage, it was possible to show that SSI of the four-­ layer bandage is in the inelastic range. It may happen that the superimposition of different components and the friction between the layers change the elastic properties of the final bandage, making it inelastic [47]. In conclusion, all these studies report a comparison between two different inelastic bandages and the reported different outcomes in terms of healing rate may depend on the greater experience of dedicated personnel in applying the four-layer bandage. The second comparison, inelastic bandages vs. elastic stockings [36–41], has many major flaws, too. First of all, it has to be underlined that the elastic stockings taken into consideration for comparison are actually elastic kits or tubular devices exerting a supine pressure of about 40 mmHg or more and higher stiffness compared to a single stocking (although always in the range of elastic material) due to the friction between the two components. In addition, the sub-bandage pressure, once again, was not measured, and the skillness of health providers, usually poor, was not reported. As a consequence, it could well have happened that a good elastic kit was compared with a poorly applied bandage. In the only one paper where the compression pressure was measured, the inelastic bandage was applied with a pressure lower than that of the elastic kit. It is completely reasonable that the elastic kit provided a better outcome: This is exclusively due to the poor application of the inelastic bandage [39]. In a few studies where compression pressure was measured [26, 39, 40], it was demonstrated that the higher the pressure the higher the healing rate and this conclusion is in favor of inelastic bandages even despite the conclusion of author’s papers. In fact, as well proved, inelastic b­ andages,


when correctly applied, exert a compression pressure definitely higher than elastic material.

12.1.5 Compression Therapy and Venous Hemodynamics The venous pressure in the legs depends on body position: It is very low in supine position, it increases in the sitting position, and it is maximal in standing position. Actually, in the sitting and standing still position the hydrostatic venous pressure results from the unbroken column of fluid that extends from the right heart to the foot that can be easily measured by calculating the distance from the right heart and the ankle in these different positions. The venous pressure is about 70–80  mmHg in standing still position both in normal individuals and in patients with venous disease. In normal subjects, this pressure decreases significantly during active movements (e.g., walking) down to 20–30 mmHg due to the combined effect of muscle pumping and venous valve function, which fragments the blood column and reduces the hydrostatic venous pressure [48]. In patients with venous insufficiency, valve failure causes the venous blood column to remain unbroken even during ambulation. As a consequence, hydrostatic pressure will mini­ mally decrease during and immediately after ambulation or could even increase in case of venous obstruction [49, 50]. This is what we call ambulatory venous hypertension (AVH), which causes venous congestion that will be transmitted to capillaries (capillary hypertension), which, in turn, will activate the abovedescribed mechanisms leading to venous ulcer. Compression therapy increases the transmural pressure increasing the extra-venous pressure. When the exerted pressure is strong enough to overcome the intravenous pressure (70–80 mmHg in normal subjects), it will narrow or occlude the leg veins. This is the prerequisite for the hemodynamic effectiveness of compression therapy. It was shown that a low external pressure of about 20 mmHg is effective in narrowing or occluding the veins in the supine position, but the compression pressure requested for veins occlusion must


rise to 50 mmHg in the sitting position and close to 70–80  mmHg in the standing position [51]. These data were confirmed by studies with magnetic resonance imaging (MRI) showing that in the standing position a pressure of 40 mmHg is not able to occlude the veins that are completely occluded with a pressure of 80 mmHg [52] defined as very strong [53]. Such external ­pressure may occlude the veins at every step during physical activity restoring a kind of valve mechanism, which reduces the AVH [14] by reducing the venous reflux [21, 22] and increasing the calf pumping function [23, 24]. In all the studies on venous hemodynamics, inelastic material was shown to be significantly more effective than elastic material. Inelastic material is able to reduce venous reflux and increase venous pumping function even at a low/ mild pressure range of 20–40 mmHg [54], which has an important implication when inelastic compression necessary to improve venous hemodynamics must be applied with reduced pressure in patients mixed arterial-venous ulcers (Fig. 12.4). Finally, inelastic material maintains its hemodynamic effect overtime despite a significant pressure drop as the stiffness of the bandage is well maintained as proved by the roughly unchanged SSI and “massaging effect” [55].

12.1.6 Is Inelastic Compression Always Mandatory for Ulcer Treatment? Looking at hemodynamics, inelastic material, exerting strong or very strong pressure, could be considered as best treatment option to maximally increase the ulcer healing rate. Actually, when correctly applied to exert a strong pressure, inelastic bandages can achieve an ulcer healing rate close to 100% in 3-month treatment, which was never reported for elastic material [56].

G. Mosti

Nowadays, we need to consider another treatment option: the adjustable compression wraps (ACW) based on Velcro® closing systems that are becoming more and more widespread. These devices are quite inelastic (Fig.  12.6) and as effective as inelastic bandages in terms of improvement of the impaired venous hemodynamics [57, 58]. At the same time, they are very easy to use and can be applied and re-adjusted even by the patients themselves after a very short wearing and education time (about 2 h) [59]. Actually, even with limited pieces of evidence, ACW have been proven to be more effective than Unna Boot bandage [60], than four-layer [61] and two-layer bandage [62] in achieving VLU healing. New adjustable compression wraps with air bladder sewed inside the device that can be manually inflated to increase pressure and stiffness (Fig. 12.7) are now available but not yet tested in the clinical setting. Elastic kits too offer an alternative option as they were shown to be effective in getting healing, especially in small ulcers of recent onset. Having said that the comparison between inelastic bandages and elastic kits is not trustable as it was burdened with major flaws but just considering the effectiveness of elastic kits in getting ulcer healing, we can realize that elastic kits were able to achieve ulcer healing in 36 to 96% of patients with small ulcers of recent onset in 3 to 4 months [23, 24, 26–29]. As ACWs, elastic kits do not require expert personnel to be applied and allow self-management. In conclusion, when assessing the best treatment option for VLU compression therapy, we do not have strong pieces of evidence in favor or elastic or inelastic materials but we have data enough to suggest inelastic material as the most effective treatment modality. In this case, we may choose between inelastic composite bandages (difficult to apply) or ACW easy to apply and allow self-management.

12  Compression Therapy in Ulcer Care


Fig. 12.6  Compression pressure recording of an adjustable compression wrap device. Also, with this device compression pressure increase by dorsiflexions, standing up, and walking is high overcoming the intravenous pressure (red line) and restoring a kind of valve mechanism. The succession of small circles and ellipses represents veins narrowing/occluding at every muscle contraction

during physical exercise. DSI: Dynamic Stiffness Index is the difference between diastolic pressure and systolic pressure performing foot dorsiflexions in supine position; SSI: Static Stiffness Index is the difference between standing and supine positions. WPA: Walking pressure amplitude is the difference between systolic pressure and diastolic pressure while walking

When these options are not available, for different reasons (from lack of educated personnel to lack of suitable materials), elastic kits may offer an alternative effective solution, especially in case of small ulcers of recent onset.

of superficial venous incompetence combined with compression therapy was shown to prevent ulcer recurrence more effectively than compression therapy alone with a significant difference [64, 65]. Compression therapy is anyway effective in VLU recurrence prevention. Elastic stockings are used in this indication with the highest tolerable compression [66]. Compliance with compression by elastic stockings must be taken into consideration as it was shown to be even more important than compression pressure [67].

12.1.7 Ulcer Recurrence Prevention VLUs may recur, and the recurrence rate may be as high as 78% at 3 years [63]. Surgical correction


G. Mosti

Fig. 12.7  Compression pressure recording of an adjustable compression wrap device with an air bladder sewed in the inner part and inflatable at a preset pressure of 40–50 mmHg. Also, with this device, compression pressure increase by dorsiflexions, standing up, and walking is high overcoming the intravenous pressure (red line) and restoring a kind of valve mechanism. Notice that stiffness indexes (SSI and DSI) are higher than with the standard wrap (Fig. 12.6) despite a lower compression at applica-

tion. The succession of small circles and ellipses represent veins narrowing/occluding at every muscle contraction during physical exercise. DSI: Dynamic Stiffness Index is the difference between diastolic pressure and systolic pressure performing foot dorsiflexions in supine position; SSI: Static Stiffness Index is the difference between standing and supine positions. WPA: Walking pressure amplitude is the difference between systolic pressure and diastolic pressure while walking

12.2 Special Circumstances

improves venous hemodynamics and arterial inflow even if it is still considered possibly harmful for arterial inflow and still represents a contraindication for CT in many papers [69]. Actually, some data confirm that compression therapy is possible in patients with mixed ulcers and moderate arterial impairment defined by an ankle-brachial pressure index 50 or ankle perfusion pressure  >  60  mmHg. In these circumstances, it was shown that a reduced ­compression pressure, not >40 mmHg, does not impair toe pressure [70], exerts beneficial effects on arterial flow both in the peri-wound skin and distally to the bandage [71] and is well tolerated

12.2.1 Compression Therapy and Mixed Leg Ulcers An arterial impairment affects about 15–20% of patients with venous leg ulcers [4, 68], causing a delayed healing. Only a minority of these patients are affected by critical limb ischemia that must be considered an absolute contraindication for compression therapy and represent a clear indication for surgical referral for the limb revascularization. In all other cases, when the patients suffer from a moderate peripheral arterial disease, CT

12  Compression Therapy in Ulcer Care

[72]. In addition, this modified reduced compression by inelastic material significantly increases venous ejection fraction [71] and may be considered as the basic treatment modality in managing patients with mixed ulcers. In conclusion, several papers support the effectiveness of increasing the healing rate of mixed ulcers by a reduced compression therapy, mainly by inelastic material [68, 70–75] but also by graduate [76] or progressive [77] elastic compression stockings.

12.2.2 Compression Therapy in Vasculitic Ulcers


sure of about 20 mmHg is enough to occlude the veins, but in case the patient is able to perform some physical activity and sit in a chair, a higher compression pressure is necessary to occlude the veins: around 50  mmHg in the sitting position and 70  mmHg in the standing position [51]. In this case, only inelastic material is able to exert this pressure without causing pain or any other skin damage. In conclusion, elastic compression, even with a low pressure, is effective in completely immobile bedridden patients but when they are partially immobile and still maintain some mobility they would need inelastic compression [81, 82].

Compression therapy is not only effective in improving the impaired venous hemodynamics 12.2.4 Contraindications and improving arterial inflow. It is also effective to Compression Therapy in improving microcirculation and significantly increasing blood cell velocity [78], which in gen- They are very few. Practically, we can say that the eral improves tissue perfusion (always beneficial) only true contraindications to compression therand, specifically, could reduce circulating immu- apy are limited to severe arterial disease, the so-­ nocomplex deposition another pathophysiologic called critical limb ischemia, severe heart failure, mechanism in vasculitic ulcers. Another very and severe diabetic neuropathy with sensory loss important effect of compression therapy is the or microangiopathy [83]. Critical limb ischemia reduction in inflammatory mediators and the is characterized by severe pain at rest and acral increase in anti-inflammatory mediators [79, 80]. skin necrosis, ankle-brachial ankle presThese mediators have an important role in pro- sure 40 cm/s. ABI > = 0.7 + biphasic flow CT Angiography with optimal values being: At least 1 accessible leg artery CTPO2  50%) and therefore may not have enough donor skin available to provide complete wound coverage following primary excision. A section of the patient’s own skin is sampled and grown in a laboratory. It can take several weeks to become ready for use. This technique is expensive, and once the new skin is ready for use, it must be applied immediately, regardless of the status of the recipient wound beds. CEA also requires up to 2 weeks of immobility following application, including interruption of all OT/PT

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range of motion activities, exercises, and functional mobility. Even mobilization and positioning with nursing staff are minimalized [3]. Patients with burn injuries involving superficial, partial-, or full-thickness skin with potential extension into fascia, muscle, or bone are at higher risk for scar contracture and often require reintervention. These burns can result in impairments such as loss of joint ROM, peri-articular or intra-articular joint changes, sensory loss, edema, pain, impaired ventilation/aerobic capacity, impaired activity tolerance, impaired balance, coordination, and strength. They can cause functional deficits such as impaired mobility, difficulty performing activities of daily living (ADLs), and instrumental activities of daily living (IADLs).

28.3 The Minimal Invasive Modality Treatment (MIMo) for Burn Care Surgical debridement/excision is associated with several drawbacks such as significant blood and heat loss and it is hindered by poor selectivity, which means both viable and necrotic tissue may be excised. In order to overcome these limitations, several alternative techniques for eschar removal have been developed over the years, including hydrosurgery and enzymatic debridement. None has currently become the standard of care. NexoBrid, a bromelain-based type of enzymatic debridement, has gained popularity in recent years. The term MIMo refers to a minimal invasive approach for burn care based on the use of a selective enzymatic escharolysis, which can preserve uninjured dermis and reduce the need for grafting. In addition to this, the potential wound healing capacity of stem cells can be used to favor spontaneous re-epithelization.

28.3.1 Enzymatic Selective Escharolysis The use of plant-based products for burn treatment dates back to 1600 BC. The Egyptian Smith

28  Minimal Invasive Modality (MIMo) in Burn Wound Care


Papyrus describes the use of resin and honey for the 1970s and 1980s. However, treatment with treating burn wounds. By 1500 BC, other herbal Travase led to an increasing number of wound remedies such as Cyperus esculentus had been infections soon after the application of the added to the list of substances for treating burns. enzyme. A possible postulated reason for this However, it was not until 1940 that enzymes of side effect was the need for a moist environment, plant origin were used for eschar removal. At which stimulates bacterial growth. To compenfirst, papain was extracted from the juice made sate for this adverse effect, simultaneous treatusing the fruits and leaves of Carica papaya. ment with antiseptic substances such as silver Papain was activated by adding either sulfadiazine or mafenide is recommended. ­triethanolamine or cysteine hydrochloride with Moreover, depending on the debriding effect in sodium salicylate. All of these solutions had a that case, the patient needs to be treated in a moist strong debriding effect. Guzman et  al. used environment for 3–10 days, which is a long treatpapain solution on wet surgical gauze as dressing ment time. The debridement effect can be accelfor burn wounds without any additional activator erated by applying Travase twice a day instead of and achieved satisfactory debridement results. In once and by starting application on day 1 postaddition, an enzyme made from fig tree latex burn. Using this process, full debridement can be (debricin) showed a rapid debridement effect on obtained within 24  h. Wound closure can be second-degree burns; however, no further investi- achieved faster by autologous skin grafting than gation was performed due to lack of standardiza- with standard conservative treatment. This made tion. Currently, bromelain-based products are Travase the most commonly used enzyme in commonly used in most parts of the world. American burn units until it came off market in Another group of enzymes with debriding the 1990s. properties has bacterial origin. In 1951, Altemeier Another non-surgical method for the debrideet al. described enzymes derived from Clostridium ment of eschar involved the use of acids, mainly histolyticum, Escherichia coli, Pseudomonas pyruvic acid and phosphoric acid, until the 1960s. aeruginosa, and Bacillus proteus. In vitro and An obvious disadvantage of this therapy was in vivo collagenase made from Clostridium histo- uncomfortable, painful, and long-lasting debridelyticum showed the most potent effects. The only ment. Therefore, this approach was abandoned such product with Food and Drug Administration and replaced by early surgical eschar removal in approval in the USA is clostridial collagenase the 1970s. ointment (CCO) (Santyl). There is evidence for During 1965–1979, several scientific CCOs’ positive effect on burn wounds. The find- groups examined additional enzymes such as ings suggest that CCO can be used to debride trypsins, chymotrypsins, and fibrinolysin-­ burn wounds with less pain and nursing labor desoxyribonuclease. These enzymes prevented than traditional therapy with other silver-­ wound infection but did not reach relevant impregnated products. However, large random- clinical use. Vibriolysin extracted from Vibrio ized controlled trials are needed in the future to histolytica and blowfly larvae extracts met the draw definitive conclusions. In contrast, strepto- same fate. kinase and streptodornase (Varidase) showed disSearching for an agent that could supersede appointing results, especially in the case of surgical debridement, Klasen et  al. reported in debridement of full-thickness burns. This is why 2000 that chemical or enzymatic debridement they have not gained acceptance in burn therapy had not yet achieved the status of general appli[4]. cation. The main reasons were poor quality, high Garret was the first to publish a study on neu- variability of composition, and lack of standardtral proteases made from Bacillus subtilis (suti- ization of enzymatic treatment. With the help of lains) in 1969. Over 100 patients were treated novel technologies in enzyme extraction and efficiently using sutilains. Under the tradename processing, these obstacles have now been Travase, sutilains gained increasing attention in overcome.


In the field of burn research, bromelain has gained the most attention during the last decade. Thus, it is the only enzyme that has achieved general application in Europe. NexoBrid (NXB), formerly known as debriding gel dressing (DGD, Debridase, or Debrase), is an enzymatic debriding orphan drug derived from the pineapple bromelain group of enzymes. The lyophilized dry powder enzyme is mixed with a vehicle gel to be applied onto the burn wound and covered with an occlusive dressing for 4  h. The active enzymes cannot penetrate intact keratin, its activity is limited to a few hours, and together with its eschar specificity, it has been proven to be a safe and effective debriding agent that usually completes the debridement phase in a single 4-h application. NXB specificity and selectivity to burn eschar offer the physician the option to apply it on burned surfaces and to completely debride the eschar without the need for an initial diagnosis of burn depth and without committing to a diagnosis-based surgical treatment plan involving excisional debridement and skin grafting. It is applied to the area of burnt skin after the wound has been appropriately prepared. It should only be used in specialized burn centers and should not be applied on more than 15% of the patient’s total body surface area. For a burn wound area of 100 cm2, 2 g/20 g gel is used. For a burn wound area of 250 cm2, 5 g/50 g gel is used. It should be used within 15 min after mixing and should be left in contact with the skin for 4 h. Several published studies have assessed its efficacy and safety on burn wounds. Its advantages, compared to the standard of care, include decreased surgical morbidity and blood loss, length of hospital stay, rates of infection, need for skin grafting, and costs. In addition, this product allows eschar removal without sacrificing viable or healthy tissue, returning entirely vital dermal or subcutaneous tissue. Such selective debridement allows maximal exploitation of the dermal and epidermal salvaged component’s regenerative potential and subsequent wound healing by dermal epithelialization,

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offering an option for a minimal invasive modality (MIMo) for burn care [5].

28.3.2 Stem Cell Use in Burns Recent years have seen advancements in regenerative medicine for burn wound healing encompassing stem cells and stem cell-derived products such as exosomes and conditioned media with promising results compared to current treatment approaches. Different sources of stem cells have been utilized in regenerative medicine within the scope of burn wound healing, such as embryonic stem cells (ESCs), umbilical cord stem cells (USCs), mesenchymal stem cells (MSCs) (such as bone marrow-derived mesenchymal stem cells (BM-MSCs), and adipose tissue-derived mesenchymal stem cells (AD-MSCs), burn-derived mesenchymal stem cells (BD-MSCs)) epidermal stem cells (EpSCs), and hair follicle stem cells (HFSCs). Stem cells utilize various pathways for wound healing, such as PI3/AKT pathway, WNT-β catenin pathway, TGF-β pathway, and Notch and Hedgehog signaling pathway. The therapeutic potential of stem cells for burn wound healing arises from their ability to modulate the release of the chemokines, cytokines, and growth factors necessary for wound healing. Furthermore, it is increasingly being accepted that rather than post-­ engraftment differentiation and proliferation, the therapeutic effects of stem cells lie in the secretion of paracrine or signaling molecules. Not only have stem cells shown effectiveness in acute care, but they have also shown therapeutic potential in scarring. Scarring is one of the long-term outcomes after burn and has remained a consistent challenge to overcome [6]. Burn scars tend to be thick, painful, and itchy, causing contractures and limited functionality of the injured area. Stem cells help in reducing scars inhibiting the activity of keloid fibroblasts through paracrine signaling. The treatment is provided either as direct injections or embedded in a natural/artificial scaffold.

28  Minimal Invasive Modality (MIMo) in Burn Wound Care


28.3.3 MIMo Operative Technique MIMo approach consists of a first step that is performed within 48 h from the burn event; the patient undergoes an enzymatic debridement using NEXOBRID ®. It is spread in sedation at bedside or in an operating room, on a maximum of 35% of TBSA of the patient each time; following application of NXB, the wounds are covered with an occlusive film dressing for 4 h, which is then removed using aseptic techniques. The treated area is scraped with a sterile tongue depressor in order to remove dissolved eschar and NXB remnants. This is followed by a short wet-to-dry soaking to remove all remaining remnants and then a medication with collagenase ointment is performed. After 7  days, a pseudo-eschar is formed on the treated area, and it is removed in surgery room with hydrosurgical treatment. Subsequently, medication with a hyaluronic acid scaffold soaked with stem cells obtained through lipoaspirate is performed. Ten days later, the scaffold is removed and from that time serial dressings are performed. These steps are repeated on each burn area with the target to obtain the best wound bed to be able of spontaneous healing [7]. The main purpose of using scaffold is to mimic the skin ECM and its properties. They facilitate cell growth, organization, and differentiation into functional tissues. Scaffolds containing MSCs can provide a microenvironment suitable for cell adhesion, proliferation, and differentiation. Scaffolds are versatile and can be modified using computational modeling to withstand changes in fluid composition, cell density, and mechanical stress, as well as to help in the timely release of molecules from the matrix. Scaffolds can be made from natural materials like collagen, hyaluronic acid, fibrin, and polysaccharides such as chitosan. These materials have high biocompatibility and show enhanced epithelialization and granulation of wounds in preclinical studies [8] (Figs.  28.1, 28.2, 28.3, 28.4 and 28.5).

Fig. 28.1  31-year-old patient affected by intermediate-­ deep and deep burns caused by flame and covering over 50% of total body surface area

Fig. 28.2  NexoBrid application within 12 h of the hospital admission

28.3.4 Anesthetic Protocols and Settings of Treatment Patients must be treated in different settings depending on age, comorbidities, extension, and location of the injury. According to the setting


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Fig. 28.3  Results of the escharolysis 4 h later the application of NexoBrid. Note the absence of necrotic tissue and the preservation of vital dermis

Fig. 28.5  Postoperative picture at 30 days of follow-up. Complete wound healing has been reached through both split-thickness skin grafts and spontaneous healing

where the patient is treated, different anesthetic protocols can be used: a soft sedation with midazolam or another benzodiazepine, with 5  mg intramuscular injection of morphine for pain control, can be applied in the outpatient setting on the burns only 30 min before the application and removal of the product. Patients with a more extensive TBSA% require a controlled anesthetic procedure in the recovery room. For patients with extensive burns (where not only the upper limb is involved or depending on age and comorbidities), general anesthesia or deep sedation is performed.

28.3.5 Advantages of MIMo Compared to the SOC This technique is more effective than SOC at reducing the proportion of the deep partial-­ Fig. 28.4  Postoperative picture 4 days after the application of the debriding agent. Small island of re-­ thickness burn wounds that need surgery to remove skin tissue or require a skin graft. It epithelization can be observed

28  Minimal Invasive Modality (MIMo) in Burn Wound Care


results in faster eschar removal with reduced does suggest, however, that in the case of blood loss than the SOC. Furthermore, a reduc- moderate burns we can prevent unnecessary tion in the need for autografting is achieved incisions. because of more selective debridement, which spares the vital dermis. This again led to a reduction in donor site morbidities while achieving References comparable long-term results of wound healing 1. Abdul Kareem N, Aijaz A, Jeschke MG.  Stem in esthetics, function, and quality of life. cell therapy for burns: story so far. Biologics. Bromelain-based substance has also been seen to 2021;15:379–97. be an effective debridement treatment for burn S259124. PMID: 34511880; PMCID: PMC8418374. wounds of all thicknesses, including full-­ 2. Krieger Y, Rubin G, Schulz A, Rosenberg N, Levi A, Singer AJ, Rosenberg L, Shoham Y.  Bromelain-­ thickness wounds, and it is faster than standard based enzymatic debridement and minimal invasive treatments [9]. modality (mim) care of deeply burned hands. Ann Moreover, the management of burn patients is Burns Fire Disasters. 2017;30(3):198–204. PMID: notoriously expensive in terms of patient hospi29849523; PMCID: PMC5946757. 3. Ranno R, Vestita M, Verrienti P, Melandri D, Perniciaro talization time, surgical procedures, transfusion, G, Preis FWB, D’Alessio R, Alessandro G, Caleffi E, dressings, and other accessory therapeutic meaDi Lonardo A, Palombo P, Posadinu MA, Stella M, sures, and dedicated intensive care unit (ICU) Azzena B, Governa M, Giudice G. The role of enzypersonnel and related costs. The clinical efficacy, matic debridement in burn care in the COVID-­19 pandemic. Commentary by the Italian Society of Burn safety, and favorable cost-effectiveness of NXB Surgery (SIUST). Burns. 2020;46(4):984–5. ISSN have been demonstrated by a recent randomized 0305–4179. controlled trial. Enzymatic debridement is asso4. Greenhalgh DG.  Management of burns. N Engl J ciated with less surgery for both excising burns Med. 2019;380(24):2349–59. NEJMra1807442. PMID: 31189038. and coverage resulting in a reduction in hospital5. Jeschke MG, van Baar ME, Choudhry MA, Chung ization times and sanitary costs. These characterKK, Gibran NS, Logsetty S.  Burn injury. Nat Rev istics also result in improved patient quality of Dis Primers. 2020;6(1):11. life [10, 11]. s41572-­020-­0145-­5. PMID: 32054846; PMCID:

28.4 Conclusions In our experience, MIMo is a valuable tool for the treatment of burn wounds. The simplicity of its application, its selectivity, and effectiveness in digesting only nonviable tissue and the possibility of an early treatment and diagnosis of burn depth make an optimal management of the burn wounds possible. Saving the vital dermis and using the potential healing capacity of stem cells allow for higher rates of spontaneous re-­ epithelialization, reducing the need for autografting. Moreover, prompt enzymatic escharolysis can prevent, solve, and vicariate the treatment of compartment syndrome, lowering intra-­ compartment pressure. This does not mean that in case of severe and deep circumferential burns, escharotomy must not be performed. It

PMC7224101. 6. Shen T, Zhang LP, Wang YR, Zhu ZK, Han CM. Effect of sedation on resting energy expenditure in patients with extremely severe burns and the choice of energy estimation formula. Zhonghua Shao Shang Za Zhi. 2022;38(8):714–21. cma.j.cn501225-­20220530-­00207. PMID: 36058694. 7. Burn’s treatment 2022 Guidelines. The Brigham and Women's Hospital, Inc., Department of Rehabilitation Services. 8. Zhang B, Wu Y, Mori M, Yoshimura K.  Adipose-­ derived stem cell conditioned medium and wound healing: a systematic review. Tissue Eng Part B Rev. 2022;28(4):830–47. TEB.2021.0100. Epub 2022 Jan 10. PMID: 34409890. 9. Barrera JA, Trotsyuk AA, Maan ZN, Bonham CA, Larson MR, Mittermiller PA, Henn D, Chen K, Mays CJ, Mittal S, Mermin-Bunnell AM, Sivaraj D, Jing S, Rodrigues M, Kwon SH, Noishiki C, Padmanabhan J, Jiang Y, Niu S, Inayathullah M, Rajadas J, Januszyk M, Gurtner GC. Adipose-derived stromal cells seeded in pullulan-collagen hydrogels improve healing in murine burns. Tissue Eng Part A. 2021;27(11–12):844–56. ten.TEA.2020.0320. Epub 2021 May 27. PMID: 33789446.

306 10. Giudice G, Filoni A, Maggio G, Bonamonte D, Vestita M. Cost analysis of a novel enzymatic debriding agent for management of burn wounds. Biomed Res Int. 2017;2017:9567498. 11. Ranno R, Vestita M, Maggio G, Verrienti P, Melandri D, Orlandi C, Perniciaro G, De Angelis A, D'Alessio R, Mataro I, Pagnozzi E, Alessandro G, Caleffi E,

A. De Cosmo et al. Di Lonardo A, Ciappi S, Palombo P, Posadinu MA, Stella M, Romeo M, Minic J, Governa M, Giudice G.  Italian recommendations on enzymatic debridement in burn surgery. Burns. 2021;47(2):408–16. Epub 2020 Jul 15. PMID: 32723513.


Thermal Burns Albin Stritar and Marko Mikša

29.1 Introduction Burnt skin is an ideal medium for bacteria, so the idea of removing dead tissue is not new. Surgical ablation or surgical necrectomy reduces the amount of avital tissue and thus improves the patient’s chances of survival. Excision of the carcass was suggested in the second half of the nineteenth century (Lusgarten 1871) at the first microbiological findings that it was a favorable medium for bacteria. It was first performed by Wilms in 1901. The importance of graft coverage, after necrectomy of a burn wound, is described in Sneve 1905 [1]. The findings on the use of skin grafts were certainly beneficial (Reverdin 1871, Ollier 1872, Wolfe 1880, Krause 1893, Thiersch 1890). However, major excisions were then abandoned, due to high mortality, numerous operative complications, and poor results. A new opinion about the importance of excision was then formed only after 1960 (Jackson, MacMillan, Switzer). New patient preparations, A. Stritar (*) Clinical Department of Plastic Surgery and Burns, University Medical Centre Ljubljana, Ljubljana, Slovenia e-mail: [email protected] M. Mikša Clinical Department of Surgical Infections, University Medical Centre Ljubljana, Ljubljana, Slovenia

new findings in transfusion medicine and anesthesiology and better techniques, and work in burn centers all developed a method that technically allows for early excision between days 1 and 5 of all deep dermal and completely deep burns. This ensures healing and the best possible functional and esthetic results [2]. The method, developed by Zora Janžekovič (Fig. 29.1), was recognized all over the world and named early tangential excision. This is how burn surgery came about. Multiannual results then demonstrated that the best time for primary excision was between days 3 and 5. Any delay in excision after day 5 results in deepening necrosis, colonization of bacteria, activation of infection, and changes in blood vessels and blood components, resulting in profuse and prolonged bleeding during surgery. Even later reduced burn edema complicates the operative approach [3]. The Ljubljana School of Surgery then supplemented the method, such as the use of the Esmarch garter, the elevation of the extremities during surgery, and the use of adrenaline to reduce bleeding (Brčič and Zdravič 1979). The axiomatic rule, however, is that the necrectomy must be accurate and “healthy,” with excellent hemostasis, without drying out the wound [4]. The method later in the 1980s had numerous modifications from other authors (Baxter, Herndon, Jankiewicz), such as extension of primary necrectomy to day 7, multiple staged excision on a daily basis, narrower selection of

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



Fig. 29.1  Dr. Zora Janžekovič, the pioneer of modern burn care (1918–2015). (Reproduced from Trop M, Schiestl C. Zora Janžekovič. Z britvijo na sam vrh opeklinske kirurgije. Celovec: Mohorjeva; 2010)

patients according to burn size, and respiratory burn. Tangential excision has been combined by some authors with excision “en bloc” to the fascia (Soerensen 1976). The method is certainly still in use and an integral part of the doctrinal principle of the treatment of burns. With timely and correct excision, we achieve the healing of deep burns with a suitable cover, as well as the best functional and cosmetic result [5].

29.2 Local, Histomorphological Changes in a Burn Wound The induced thermal state causes changes in the affected tissue that decreases in intensity with depth, but gradually increases in intensity due to slow cooling until the temperature stabilizes.

A. Stritar and M. Mikša

Clinically, the changes are manifested in three zones: necrosis, stasis, and hyperemia. In the first three days, the most important changes are in the vascular system. In the zone of stasis, the following changes occur: stasis, thrombosis, wall disruption, hemorrhage, and changes in the intact arterioles. The survival of the zone of stasis depends on the restitution of the capillary endothelium and the restoration of venous outflow. Around post-burn day 3, the primarily reversible compromised tissue is definitely destroyed. The body reacts to such changes with inflammation, which accelerates tissue deterioration. The progressively deepening necrosis often turns a deep dermal burn into a subdermal burn. After post-burn day 3, under the influence of autolytic processes in the damaged tissue and the activation of the saprophytic flora in the ducts of the sweat glands and sebaceous glands, a process of demarcation begins, accompanied by destruction of the biologically, compromised tissue. The resulting complications are predominantly infection and later symptoms of a long-exposed surface. Hypermetabolism, changes in defense mechanisms, catabolic reaction, and weight loss put the patient at risk in proportion to the extent of the injury and his/her general condition.

29.2.1 General Changes The thermal state is transferred from the burnt tissue to the extravascular space via the vascular space and the endothelium of the entire capillary system. Changes occur in all components of the blood and in the capillary endothelium, resulting in disturbances in the perfusion of all organ systems. This is a dynamic process whose flow can be interrupted at any time from the moment of the first change until the end of the granulation phase or the end of the scar development phase. The success of the treatment therefore depends on appropriate first aid, primary care, and appropriate anti-shock therapy for extensive burns, timely and appropriate surgical management, and good postoperative care.

29  Thermal Burns


29.3 Admission of a Burn Patient

29.4 Burn Assessment

In addition to the burn wound, the general status and condition of the respiratory burn are important for the surgeon as part of the work and tasks in the admission of a burn patient in the anesthesia or resuscitation room. It is important to get acquainted with previous illnesses. Before carefully evaluating soft tissue status, it is very important to first identify other injuries, and ­ fractures and rule out craniocerebral trauma with impaired consciousness. We need to pay attention to internal and external bleeding. We try to calm the burn. We protect it from heat and liquid loss. While obtaining patient history, in addition to the patient’s general information, the following information is important: type of burn, place of the accident, whether the accident is indoors or outdoors, method of referral, allergies to medications, which medications the patient is taking, and previous illnesses. Inhalation injury information is important. The attached documentation and therapy are also required if the patient has previously been cared for in a specialized institution. In the anesthesia room, we also take care of the peripheral and central venous canal for fluid therapy and later parenteral nutrition, swab collection, and blood collection for laboratory tests. In the dressing room, under anesthesia or analgesia, we perform a bath and a mechanical toilet. This is followed by an evaluation of the burn. After the final assessment and graphic presentation of the burn, the burnt surfaces are wrapped with compresses, and a nasogastric tube and a urinary catheter are introduced. In severe burns, the patient remains intubated. Tracheotomy follows laryngeal edema, extensive facial burns, and expected prolonged intubation. Before placing the brick in the intensive care unit, we must think about preventing bedsores, so on special beds the exposed parts are lined with pillows, the extremities are immobilized and slightly elevated, and placed in anti-contractile positions.

The surface extent of a burn, measured as a percentage of the burned body surface area, is the first major practical criterion for triage. In addition, the decision on the question of where and how we will treat the burn is based on its depth and localization. This is an extremely important piece of information for the anesthesiologist at admission and later the intensive care specialist in the ward. Upon admission, a scheme of the burn is drawn, which is also an official document, in terms of dimension and depth. Uniform criteria must be used to avoid misunderstandings. When assessing the area, erythema is excluded and only burnt skin is assessed. It is by no means a problem if the surgeon re-marks the scheme the day after admission or later. A simple rule employed is “number 9”, a tool to assess the total body surface area (TBSA) involved in burn patients. The Rule of Nines estimation of body surface area burned is based on assigning percentages to different body areas (Wallace 1951) [6]. The percentage difference is in children, where the whole head is rated higher than in adults, while the lower extremities are smaller compared to adults. The Lund-­Browder scheme (1944), which is a modification according to Berkow (1924), draws the depth of the burn in addition to the percentages [7]. With novel software technologies, many new schemes are being developed to achieve the fastest results [8]. According to the final assessment of the area in burns, we distinguish: –– Minor burns (up to 10% of total body surface area). –– Moderate burns (up to 20% of total body surface area). –– Severe burns (20–60% of total body surface area). –– Critical burns (over 60% of total body surface area).


A. Stritar and M. Mikša

Fig. 29.2  Level of the necrosis in various skin burns is shown. D dermis, (a) superficial dermal burn, (b) deep dermal burn, (c) subdermal burn (Reproduced from Mirko Derganc ed. Present clinical aspects of burns – a symposium. 1968, Slovenia, p. 139)


b c

In describing the depth of the burn, instead of the three-level American classification (1953), the anatomical classification is more useful. Burns are divided into epidermal, dermal, and subdermal (Derganc 1972) (Fig. 29.2) [9]. For important practical reasons, depending on the prognosis and therapy, a distinction must be made between superficial and deep dermal burns in dermal burns. Epidermal and superficial dermal burns with good capillary refill and with a perceived sense of pain are not a surgical problem. Deep dermal burns and subdermal burns, however, dictate surgical treatment, such as surgical removal of dead tissue, usually within the first five days after the burn trauma. The localization of burns is also important, thus distinguishing functional areas such as face, neck, feet, shins, genitals, perineum, and mucous membranes and non-functional areas such as torso, shoulder, and buttocks. When planning an operation, functional areas have priority. Regarding the soft tissue status, the surgeon must pay attention to circular burns, where consequent edema, especially in children, compresses the extremity area. This is most often seen in the wrists, elbows, and ankles. Blood flow

should be monitored distally from conception or even surgery should be performed. At the time of admission, we must be especially careful if a deep burn of “eschara” compresses the underlying soft tissues and neurovascular structures and thus threateningly increases tissue pressure. In this case, it is imperative to perform an escharotomy to the muscles along typical incision lines. The incision must be complete, with precise hemostasis. Surgically, an incision of the upper extremity, lower extremities, and thoracic incisions is made to establish the respiratory mobility of the thoracic wall. Bronchoscopy is also indicated for respiratory burns that worsen the prognosis of treatment.

29.5 Surgical Treatment of Burns The best way to organize the treatment of burns in a larger region is a burn center. Treatment of large burns requires highly qualified personnel and equipment, which is often difficult to provide. Treatment is multidisciplinary, long-lasting, expensive, and with a high disability. Intensive

29  Thermal Burns

treatment of large burns before, during, and after surgery in shock requires a multidisciplinary team, which includes in addition to the surgeon also anesthesiologists, pediatricians, dieticians, intensivists, nephrologists, psychiatrists, and psychologists [10]. The surgery requires an experienced team of surgeons, a complete instrumental team, which can be doubled, and an anesthetic team. Regarding treatment in shock, the doctrines in the larger centers differ, with the burn being treated in some places by surgeons, and in other places by anesthesiologists or specialist intensivists. Primary excision in the first 24  hours is indicated: 1. In subdermal burns, if patients are in good condition. 2. In electrical burns, in which deep structures are affected. 3. In combined injuries, in which necrosis is excised at the site where the incision is required, and the wound after the completed procedure is covered with. 4. Autografts for extensive burns on the extremities due to the constrictive effect of ESCHAR. 5. In critical burns. 6. In burns that do not respond to anti-shock therapy. When organizing the operation, operative teams must be provided, the anesthetist must be informed about the operation and the general condition of the patient. Blood must be ordered and skin must be provided. Substitutes to cover operated sites should be available. The plan of surgery should be clear, due to the location of the patient, excised sites, retrieval sites, additional dressings during surgery, tracheostomy replacement, catheters, and organization of additional nursing teams. The participation of the entire team during the operation must be active and coordinated, due to the movement of electrodes and catheters, turning the patient, due to increased blood loss, control of the arterial canal, and due to the risk of hypothermia. The excision method is consistent with the requirement that only irreversibly damaged tis-


Fig. 29.3  Primary tangential excision of burn wound

sue should be removed to the clinically vital surface on which the grafts are fully grown. Hemostasis must also be meticulous. If both conditions are not met, the grafts do not grow primarily and less valuable granulation tissue grows. Excision must be definitive and systematic in the transition from one region to another (Fig. 29.3). As a rule, only deep burns are excised in the operative field. However, superficial burns are excised only exceptionally if there are deep burns in the middle. On the eighth day, all such superficial dermal burns become deeper, due to damage to the wall and the path in the larger veins and irreversible damage to the collateral circulation. The end result of necrectomy is a clean wound with a vital base, and the biological potential of the excised surface is reduced by 20% (Janžekovič 1977). Such a wound further necrotizes due to dehydration and deepens, so we cover it with grafts. Covering follows immediately after surgery or at the latest after 24 hours. As a rule, autografts are harvested before excision of the carcass [3, 9]. The only definitive biological cover is its own skin graft (autotransplant), which primarily grows into the defect and to a greater or lesser extent replaces the destroyed skin (Fig. 29.4). In insufficient quantities of autografts, we use temporary grafts such as cadaver skin (homograft and allograft) and xenografts or heterografts such as semisynthetic dermis and amniotic membranes. The strategic plan for a large burn (60% of the body surface) would be as follows: In the first


Fig. 29.4  Use of autologous skin graft is the gold standard for surgical management of burns

surgery, a necrectomy of the largest possible area is performed (the limit is blood loss or coagulation and the general condition of the patient). Then performed the excised areas with autografts, with functional and esthetically important areas having priority. If there are not enough autografts, we use homotransplants from the skin bank. Before infection and spontaneous lysis of homotransplants occur, which usually occurs after a week to ten days, they are replaced with homotransplants from another donor. Then, gradual replacement of homotransplants with autografts takes place, which can be taken several times from the same donor areas at intervals of 7–10 days, until the patient is completely covered with his skin. It should be noted that mesh graft growth is significantly better than a complete graft, due to hematoma drainage. The mesh graft can also be more or less stretched. With the mentioned technique of creating mesh, stretched skin grafts, we can excise most of the burned area in one to two operations and thus economically cover the wound with autografts. This prevents the wound from drying out and bacteria from invading. Even when using laboratory-grown skin, the procedure is similar. After three weeks, when the skin is grown and the wound is covered with it, we do not remove the homographs completely, but serve as a neodermis, or a connective base for the grown keratinocytes. Cultured keratinocytes

A. Stritar and M. Mikša

deposited directly on the vital fatty subcutaneous tissue lyse in a higher percentage. In recent years, novel technological solutions emerged as alternatives to standard grafting techniques. The RECELL® Autologous Cell Harvesting Device (RECELL® System, AVITA Medical, Valencia, CA, US) was developed to minimize the amount of healthy skin to achieve definitive closure of burn injuries. It is developed for point-of-care preparation and application of a suspension of non-cultured, disaggregated, autologous skin cells, using 1 cm2 of the patient’s skin to treat up to 80 cm2 of excised burn. It can also be used in addition to normal skin grafting in order to maximize results and graft intake [10]. Another technique used to optimize and maximize donor skin to cover large burns is the Meek micrograft technique. Although mentioned in the early 1953, before the invented mesh technique, a young doctor Cicero Parker Meek published using a partial-thickness skin expansion device, called a micrograft. It cut skin to small islets that were later transferred to the wound bed. During this time, the Meek micrograft was forgotten, until the 1990s when it was renewed and improved by doctors in the Netherlands. Nowadays, micrografting can be used when there is poor bed vascularity, such as in patients with diabetes, with a greater success rate due to low metabolic demands [11, 12]. Skin substitutes have important roles in the treatment of dermal and full-thickness wounds, including burns. At present, there is no ideal substitute in the market that provides an effective and scar-free wound healing. Further research should be carried out not only to compare different skin substitutes but also to evaluate new biological and synthetic materials that can be utilized in wound healing [13]. There have been many interventions using different types of stem cells and stem cell-derived products to promote better healing and minimize recipient defects. Even with promising results in experimental studies, there is still a lack of enough published clinical trials to make an inference about the safety and efficacy of stem cells in burn wound care [14].

29  Thermal Burns

29.6 Postoperative Care


splinted or positioned and feet kept at 90 degrees, and care and attention must also be given to the This is an important part of rehabilitation and is heel area, which can quickly develop pressure. divided into sub-acute, acute, and chronic phases. Legs should be positioned in a neutral position In the acute phase, treatment of burns is com- ensuring that the patient is not externally rotating bined, using dressings, antibiotics, antiphlogis- at the hips [18]. The hand exercise program begins immeditics, and analgesics in superficial burns, and early ately. The active mobilization is first physiologiexcision of necrotic skin cover in deep burns cal, followed by passive mobilization. The (Fig. 29.5) [15–17]. Physical therapy is essential for a burn patient, exercise therapy is carried out according to a prostarting from the day of injury and lasting for the tocol, taking into account the patient’s condition entire duration of treatment. The aim of physical and the burn injury timeline (Moore et al.). Simultaneously, occupational therapy is rehabilitation is to improve the functional indeincluded throughout the rehabilitation process in pendence of the burn patient by restoring the order to prevent deformities and improve the functional ability of the hand or minimizing the functional status. Occupational therapy includes loss thereof. Scar management after sustaining a burn injury is a lengthy process. Among the main applying splints, both static and dynamic, moniphysical therapy, assessment procedures are mea- toring scar maturation, hydrotherapy, use of ointsurements of joint mobility, massage, ultrasound ments and creams, applying compression therapy, laser therapy, therapeutic exercises for garments and simultaneous education. Passive, the extremities, and patient education Moore static splints have multiple functions, such as immobilization of the affected body part, and et al. [16]. It is of most importance to start anti-­ maintaining an optimal and functional position. contracture positioning and splinting from day Splints prevent development of contractures. The function of dynamic splints, however, is to regain one and continue for many months thereafter. Positioning is important to influence tissue and restore the affected hand function. Finally, length by limiting or inhibiting loss of range of scar management is a function of physiotherapy motion secondary to the development of scar tis- and occupational therapy, with the goals of reducsue. Elevation of all limbs affected is necessary in ing hypersensitivity of scars, softening scarred order to quickly reduce edema; hands should be tissues, preventing scars from raising above the Fig. 29.5 Postoperative care includes vital functions monitoring, fluid replacement, medication, and frequent dressing change


skin level, preventing and reducing contractures, and, finally, psychosocial education with regard to coming to terms with scarred skin (Moore et al.; Callahan et al. 1988; Cowan et al. 2013).

29.7 Conclusion It is typical for the treatment of burns that the treatment is long-lasting and expensive and that the disability is still very high. The operational technique itself has advanced, as has the instrumentation. Of course, there are new possibilities in bioengineering, where not only ­laboratory-­grown keratinocytes or semisynthetic dermis but fully cultured skin with dermis, epidermis, and derivatives will represent the optimal solution for your own skin graft. Burn surgery is seemingly very simple, but it requires a tremendous amount of experience, skills, immediate solutions, anticipation, and timing. Even further reconstructive procedures, after the acute phase, require the complex knowledge of a plastic surgeon, who thus operationally establishes the entire algorithm of surgical burn therapy. Good teamwork, careful preparation for surgery, professional anesthesia during surgery, and postoperative intensive care are postulates for a good result and survival of a large burn. Finally, we must not forget the humane and kind attitude toward the burnt patient, who can also be a child and isolated in the room with his anxiety, fear, and pain. The moral support of the surgeon, anesthesiologist, and all employees is irreplaceable for the patient if we want to achieve success in treatment.

References 1. Sneve H. The treatment of burns and skin grafting. J Am Med Assoc. 1906;47(1):1–8. 2. Switzer WE, Sixth National Burn Seminar. Wound management. Use of homografts. J Trauma. 1967;7(1):79–86. 3. Janzekovic Z. The burn wound from the surgical point of view. J Trauma. 1975;15(1):42–62.

A. Stritar and M. Mikša 4. Brcić A. Primary tangential excision for hand burns. Hand Clin. 1990;6(2):211–9. 5. Baxter CR.  Management of burn wounds. Dermatol Clin. 1993;11(4):709–14. 6. Moore RA, Waheed A, Burns B.  Rule of nines. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2021. 7. Lund CC, Browder NC.  The estimation of areas of burns. Surg Gynecol Obstet. 1944;79:352–8. 8. Chong HP, Quinn L, Jeeves A, et  al. A comparison study of methods for estimation of a burn surface area: Lund and Browder, e-burn and Mersey Burns. Burns. 2020;46(2):483–9. burns.2019.08.014. 9. Derganc M.  Classifying burns. Br J Plast Surg. 1970;23(3):209–10. s0007-­1226(70)80043-­1. 10. Holmes JH 4th, Molnar JA, Shupp JW, et  al. Demonstration of the safety and effectiveness of the RECELL® system combined with split-­ thickness meshed autografts for the reduction of donor skin to treat mixed-depth burn injuries. Burns. 2019;45(4):772–82. burns.2018.11.002. 11. Rijpma D, Claes K, Hoeksema H, et  al. The meek micrograft technique for burns; review on its outcomes: searching for the superior skin grafting technique. Burns. 2022;48(6):1287–300. https://doi. org/10.1016/j.burns.2022.05.011. 12. Ottomann C, Hartmann B, Branski L, Krohn C. A tribute to Cicero Parker meek. Burns. 2015;41(8):1660– 3. 13. Halim AS, Khoo TL, Mohd Yussof SJ.  Biologic and synthetic skin substitutes: an overview. Indian J Plast Surg. 2010;43(Suppl):S23–8. https://doi. org/10.4103/0970-­0358.70712. 14. Abdul Kareem N, Aijaz A, Jeschke MG. Stem cell therapy for burns: story so far. Biologics. 2021;15:379– 97. Published 2021 Aug 31. 15. Young AW, Dewey WS, King BT.  Rehabilitation of burn injuries: an update. Phys Med Rehabil Clin N Am. 2019;30(1):111–32. pmr.2018.08.004. 16. Cowan AC, Stegink-Jansen CW.  Rehabilitation of hand burn injuries: current updates. Injury. 2013;44(3):391–6. injury.2013.01.015. 17. Dodd H, Fletchall S, Starnes C, Jacobson K. Current concepts burn rehabilitation, part II: long-term recovery. Clin Plast Surg. 2017;44(4):713–28. https://doi. org/10.1016/j.cps.2017.05.013. 18. Richard R, Baryza MJ, Carr JA, Dewey WS, Dougherty ME, Forbes-Duchart L, et  al. Burn rehabilitation and research: proceedings of a consensus summit. J Burn Care Res. 2009;30:543–73.

Part V Measurement and Documentation

Imaging and Measurement


Jacopo Secco

30.1 Introduction As in all medicine research fields, the importance of a newly developed solution is measured through the gravity of the problem. Regarding chronic wounds, it is a fact that kin ulcers are a chronic pathological condition affecting around 1–2% of the world’s population [1]. In Europe alone, over four million patients are affected by this syndrome, costing =C4 billion in national health treatment every year. Primarily found in people > 65 years of age (> 60%), skin ulcers are commonly associated with preexisting chronic diseases such as diabetes, vascular problems, heart disease, and obesity [2]. Early detection and assessment of the wound are vital; after four weeks, there is a 30% chance of the lesion never healing, a 50% chance of loss of limb and a 50% chance of mortality in the following 5 years [3]. Chronic pain, reduced mobility, and psychological and emotional stress are just a few of the difficulties commonly experienced by patients with this skin condition. Furthermore, treatment of skin ulcers may prove lengthy, taking several months or even years for the wound to heal [4]. In many patients, complications arise that require urgent surgical intervention leading to long periods of hospitalization [5]. J. Secco (*) Department of Electronics and Telecommunications, Politecnico di Torino, Torino, Italy e-mail: [email protected]

From the presented data, it is clear that there is the need in common clinical practice regarding chronic wounds of tools that can assist the caregivers in delivering the required amount of assistance to their patients. A recent study has shown that through the use of medical devices and standardized procedures that helped the physicians and the nurses simply to communicate more efficiently, the results of the delivered cures have substantially increased the healing rate from 75% to 90% of the overall cases. The same study has also demonstrated that the same approach has led to a decrease in the cost of cure by 35% due to more precise prescriptions and an increased control of the cure plans [6]. These results are surely encouraging and are the outcome of the last 20 years of research in the field [7]. From the work of Bekara et al. [7] and from even a more recent review of the new wearable technologies for ulcer management and assessment by Wang et al. [8], it is clear that the keywords are essentially two: measure and communicate. Obviously the first leads to the second, but it also sub-intends another essential requirement: standardization. In this last decade the world of medicine has seen great technological evolution, not only regarding diagnostic means, but also regarding methods of transmitting the information remotely and in a precise fashion. The birth of telemedicine and its conquest of a fundamental role in future diagnostics and patient care due to the COVID-19 pandemic

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



taught a valuable lesson not only to the caregivers, but also to the whole hospital management community [9, 10]. In order for this to happen, it is crucial that the information that is gathered from a patient must be extremely precise and complete in order to perform the best possible assessment. Leading the discussion back to ulcer cure, one of the fundamental milestones that technological assessment has reached is the standardization of the clinical information regarding the assessment. Quantification in wound care is a gray area in which many works have been published, but authors have yet to reach a consensus. A number of parameters are measured. The work of Mani et al. remains one of the cornerstones, listing the various measurement possibilities [11]. The pH is intended to be an indicator of tissue repair, considering also its role in the microenvironment of the wound bed [12]. Transcutaneous oxygen and flow at the microcirculatory level are important, but only as indicators of possible results in terms of tissue vitality. The fact that a skin ulcer has a defined area and volume, although not simply measured, has led many authors to further investigation. For clinicians, the objective of measuring is to be able to better define the evolution of a wound, whether it is being repaired, blocked, or worsened; Flanagan et  al. define wound reduction parameters as repair indicators [13]. Sheehan et  al. have demonstrated that, in the case of diabetic ulcers, early assessment (within four weeks) is crucial for full recovery [3]. Gorin et  al. have analyzed the reduction of wound, area, width, and length, and concluded that a linear parameter is independent of the geometric shape of the wound [14]. Cukjati et  al. reiterate how wound area and its variations indicate evolution and prognostics [15]. Moreover, the percentage change of the wound area is a clinically recognized prognostic measure, although the problem remains of how to measure it [16, 17]. Wound area is not the only prognostic indicator. Solutions have been developed that propose a subdivision of the lesions— in terms of tissue type and exudate management—may be considered an appropriate indicator of clinical results. One of the most com-

J. Secco

monly used is the wound bed preparation (WBP) score proposed by Falanga as an analysis parameter as it is well-known and used on different types of wounds [18]. As shown, ulcer assessment can take into account many different variables, and an accurate relation among them can surely lead to an always more complete wound classification in diagnostic terms. In any case as mentioned by Khoo et al. and by Haghpanah et  al., the capability to perform a correct morphological measurement of the wound and its variations in its healing process is one of the key elements for a correct diagnosis. In these terms, the evolution of wound treatment techniques has been followed by a parallel evolution of the imaging and measurement devices for wound treatment [19]. Just in the last ten years, different solutions have been developed, trialed, and brought to the market, entering one by one in the standard procedures for wound treatment, always increasing their efficiency and precision. The following sections will deliver an overview of both imaging and measurement techniques used in wound care nowadays, due to their proven diagnostic significance. The devices and the procedures that are here described set the actual standard of cure and show a glimpse of the future of this always developing field. The final goal is to give a better understanding of the future of wound assessment and how technology can help the caregivers, which are always working in the front line, to render an always higher standard of cure meeting the ongoing life and social requirements.

30.2 Overview of Imaging Technology in Wound Care In order to measure something, it is necessary first to feel it, or even better, to see it. Historically, seeing something under the skin has been one of the major problems to overcome. At first physicians were obliged to look for different symptoms by touching the patient, searching for cutaneous eruptions, rashes, or wounds, or even to auscultate the body by laying the naked year on the patient’s skin. These methods were the

30  Imaging and Measurement


only available until the eighteenth century for obvious reasons. The main, and probably the only, reason was that it was thought to be unnecessarily dangerous to cut open the skin to simply look inside the body unless no other solution was possible. As a matter of fact, instant cauterization techniques such as the electric scalpel did not exist until the 1920s. For this reason, the first studies of the human anatomy and physiology in Europe were conducted by dissecting dead bodies. Moreover, the first anatomists also had to have an outstanding artistic talent since all their observations had been hand-drawn for future studies. Two of the most famous artists and anatomists lived between the end of the fifteenth century and the first half of the sixteenth century were Andreas von Wesel (a.k.a. Andreas Vesalius) and Leonardo da Vinci, whose some of their studies arrived to us as true pieces of artwork (two examples of Leonardo’s anatomical work are shown in Fig. 30.1). In the eighteen-hundreds, two major discoveries gave birth to what today we call medical imaging. The first was the invention of photography in 1827 by Nicéphore Niépce in collaboration with Louis Jacques Mandé Daguerre. The

second was the invention of X-ray tube by Wilhelm Rontgen. The evolution of these techniques has led to the birth of the field medical imaging. This field has become so popular and so important that it is reported that by 2010 around 5 billion medical imaging studies have been conducted worldwide, and it is estimated that by 2020 these have increased by 10% [20]. Medical imaging started have a greater differentiation between its morphological and functional purposes with the advent of digital images in the 1990s. At first, all imaging techniques, not only in the medicine field, were analog. This meant that the resulting image from a camera, an X-ray machine or whatever imaging device, imprinted directly the subject of the representation on a portable physical mean. Common cameras used film rolls made of celluloid, same as the X-ray machines that initially exploited celluloid films with silver ions that had a direct reaction with the ionizing radiation passing through a body. Digitalization permitted to convert the image in a series of bits (i.e., digits, 0s and 1s) through silicon-based sensors. The obtained data can be easily stored in semiconductor-based memories such as the memory of an electronic

Fig. 30.1  Two examples of Leonardo da Vincis’s anatomical work. It is known that the famous Italian artist used to buy corpses from the dead person’s families in

order to dissect them and draw their observations. Among the many interests of Leonardo was also medicine at his arbors


J. Secco

device and can be directly analyzed using both simple and complex mathematical models. The capability of digital images to be both visualized and analyzed has increased the functionality of medical imaging. For instance, a defect detected from an analog X-ray image could not be easily measured in its size, and comparisons of the same defect detected from two different X-ray machines could not be easily performed unless the same defect presented great variations. On the other hand, thanks to the computerized tomography (CT) which is a digital X-ray machine capable of scanning the whole body dividing it into slices, it is possible to digitally reconstruct in 3D the same defect measuring it in all its dimensions. From a time development perspective, parting from the point that a first digital transformation of medical imaging devices occurred, the spectrum of functionalities that can be achieved through medical imaging devices has become exponentially greater (an example is shown in Fig. 30.2). In wound care, obviously, imaging serves as a powerful tool not only in representing the wound

per se, but also aiding the physicians and nurses to have a better understanding of the ulcer evolution. As mentioned in Sect. 30.1, wound care specialists have a need for more efficient instruments and devices in order to correctly capture the features of the lesion. These features are different and not always visible to the naked eye. Digital imaging aids the specialists in different ways, depending on the clinical parameters that are needed to be gathered. Not all the imaging techniques are commonly used in this particular field of medicine due to several factors such as the etiology of the wound, the presence of required equipment, and the actual need of distinguishing different clinical features. In any case, all the means that are nowadays used permit physicians and nurses to perform specific and precise measurements and analysis increasing the standard of care and consequently its healing efficacy. As mentioned, depending on researched clinical feature, different technologies can be exploited. These can be subdivided into two main groups that will be treated in more detail in the following subsections: optical and nonoptical imaging.

Fig. 30.2  A time functionality development graph with different examples of imaging techniques. From the advent of digital imaging, the diagnostic functionalities that can be obtained from an image have increased exponentially. As shown in the figure, traditional X-ray images

have been the state of the art of diagnostics for many years: By converting the image into digital form, imaging devices can perform complex analysis directly on the obtained data.

30  Imaging and Measurement


30.2.1 Optical Imaging in Wound Care

ment usually consists of an alloy of copper or other metals with low atomic number and is powered at low voltage; the anode (positive pole), on In general, optical imaging is the branch of imag- the other hand, located at the opposite end of the ing that exploits light of different wavelengths to ampoule, consists of a disk (plate) of heavy metal generate an image. Different wavelengths (i.e., (with high atomic number, such as alloys of tungvisible, IR, X-ray) can enhance or filter certain sten and molybdenum for conventional diagnosfeatures or objects in the final picture. The most tic tubes, molybdenum or rhodium for tubes used renown optical imaging technology in the medi- in breast diagnostics), which can be fixed or cal field is the X-ray. Discovered by Wilhelm rotating. Rotation allows for better dissipation of Rontgen, who consequently invented the X-ray the heat formed on it, which reaches temperatube, in the late eighteen-hundreds, this technol- tures on the order of 2000°C). X-ray generation ogy permits to see through the soft tissues of the occurs by Bremsstrahlung [21] (braking radiabody by emitting high-energy photons (with tion) and by characteristic radiation. In modern wavelength between 1 nm and 1 Pm). Fig. 30.3 tubes, the metal disk at the anode is rotating: This shows a—one of the first X-ray images taken by expedient lengthens the life of the tube by preRontgen (his wife’s hand with the wedding ring venting electrons, always hitting the same spot, visible), b—an example of the X-ray tube, and from prematurely eroding the electrode (“craterc—the wavelength spectrum of X-ray light. In ing” of the anode) and improves its image sharpprinciple, the X-ray tube is a glass ampoule under ness. Rotation of the anode also allows for better high vacuum that contains a cathode and a high-­ thermal dissipation, as it provides a larger surface voltage anode. The cathode (or negative pole), as area for electrons to impact. As already mentioned in Sect. 30.2, also the in ordinary thermionic valves, in turn consists of X-ray devices have passed a process of digital the heater filament and the actual cathode, which is connected to the high-voltage circuit. The fila- transformation. Until a few decades ago, this




Fig. 30.3  A brief summary of the X-ray functioning. (a) The famous X-ray taken by Wilhelm Rontgen himself: the image shows the hand of Rontgen’s wife with the wedding

ring. (b) The X-ray tube. (c) Wavelengths and some examples of X-ray uses.


generally consisted of photographic film coupled with a reinforcing screen that could impress X-rays passing through the patient’s body. Nowadays, with the advent of digital radiography, the film has been replaced by X-ray cassettes containing photo-sensible substances that will then be read by appropriate sensors and display the resulting image on a monitor. In more modern systems, an array of scintillators and charge-­ coupled devices (CCDs) are able to acquire images directly. With digital X-ray, it became possible to perform analysis directly on the image: These analyses can include the measurement of tissue morphology (also in 3D if the images are taken with a CT device) or the intensity of the given signal. An example of the last case is angiographies or in other words X-ray images of vascular districts of the patient. Through the use of a contrast (i.e., a liquid that is injected directly into the patient’s circulatory system) capable of partially reflecting photons emitted by the machine, it is possible to obtain reliable and live data on the hematic perfusion, which is one of the most crucial indicators of the insurgence or the healing of chronic wounds. Due to the limitations of X-ray imaging, the most commonly used technique in everyday wound care practice is what is called enhanced digital imaging (EDI). Usually, EDI devices consist of a normal complementary metal–oxide– semiconductor (CMOS) digital camera that, with some exceptions, works in the visible light range. These sorts of devices allow the operator to take an normal digital picture of the wound, and trough different techniques, the caregiver can perform several analyses on the lesion, such as classifying the different tissues or can perform morphological measurements and comparisons between different healing stages. As for the production of an X-ray image, visible light digital cameras can transform the intensity of reflected light from different parts of a scene. The element capable of performing this function is the sensor, which has a different form depending on the type of camera. The function that the sensor performs within a digital camera is analogous to what film does in traditional photography. From this, it is easy to understand how

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the optical part of focusing the image on the surface of the sensor retains a central role in digital photography, being responsible for the resolution of the images obtained and contributing to their quality. As aforementioned digital cameras implement a photo-sensible sensor that is responsible for transforming the analog signal of the input light into digital data. An active-pixel sensor (APS) is an image sensor in which each pixel sensor unit cell has a photodetector (typically a locked photodiode) and one or more active transistors. There are several types of APS, including the early APS NMOS and the much more common CMOS. The CMOS sensor is composed of photosites that is the smallest space within an imaging sensor with one or more photosensitive semiconductor elements capable of transforming a light flux into a given amount of electrical charges. In the photosite, in addition to the sensing element, there is usually a microscopic optical system overlying the photodetector consisting of a small crystal with a quasi-spherical dome shape having the function of capturing as much light as possible of that incident on the sensor surface. Sometimes, this crystal (or transparent resin) is an “R”-colored or “G”-colored or “B”-colored unitary element of the Bayer filter, the so-called color filter array (CFA). The photosite is also the unitary part of a larger place that is generally called a sensor. The characteristics of the photosite make it possible to understand, both electrically and optically, how the individual image-forming elements are captured. EDI’s implementing simple CMOS cameras presume several favorable functional elements that render them the most commonly used devices in wound care. The main element is the simplicity of the technology: CMOS sensors can be very small, and its technology has become extremely reliable and standardized under an implementation point of view. These sensors can be built on portable devices and do not require high energies to work, and their configuration has become extremely simple and cheap for the device-­ producing companies. The second advantage of the CMOS sensors is their functioning reliability. As reported, the sensors are neatly organized through their photosites that subdivide the image

30  Imaging and Measurement

into small basic and regular elements known as pixels. Through simple mathematical transformations, it is easy to determine precisely the physical surface that is depicted inside a single pixel of a picture. By knowing this piece of information, performing reliable and precise measures on the subject of a photography (e.g., a wound) has become easy and fast. Moreover, as in the case of the X-ray machines, having the same reference, it is consequently possible and easy to compare the size variations of the given subject with a high fidelity throughput. There is one last advantage that is given by the use of the EDIs: the standardization of the color patterns of the image. As in all digital means of depiction, the image is given by the direct transformation of the light intensity that hits the sensor into a digital signal. With the same technique colors are rendered by filtering the three main color components: red, green, and blue (RGB) through the Bayer filter of the photosite. This has become a great advantage in image analysis in wound care since color can be taken as a primary feature in order to distinguish the different tissues of a wound. If we take, for instance, into consideration the work of Falanga et al. [18], it is possible to exploit this feature in order to perform a classification of the wound through the WBP score regarding granulation. In the last ten years, different EDIs have hit the market and have been integrated into the good clinical practice in wound care. These devices can also implement other collateral sensors and emitters in order to perform other kinds of measurements (i.e., laser emitters or infrared (IR) type-C LEDs for the noninvasive measurement of the depth of the lesion). Thanks to the correct scaling of the digital picture of the wound, these devices can permit a manual tracing morphological measurement [22]. In other cases, exploiting the capability of standardizing the colors schemes of the wound, and through the use of advanced artificial intelligence algorithms, EDIs can be also capable of performing completely automatic measurements and correct clinical wound classifications [23]. The methodologies implied in wound measurement and assessment will be described in depth in the following sections of this chapter.


One last mention in the class of optical imaging technologies must be given to hyperspectral imaging (HI). This kind of imaging is usually performed with EDIs that also implement emitters of light at different wavelengths. These emitters are installed on EDIs since the emitted photons are not considered to be at high energy as the X-ray. Moreover, the reflected light (i.e., the light generated by the photons that are reflected from the surface of the illuminated skin portion) can be easily seen through optical filters or through specific sensors depending on the cases. HI devices are used for several scopes in wound care such as the analysis of the blood oxygenation of the peripheral districts or to evaluate the presence of possible infections or inflammations. Summarizing, considering the most commonly used HI technologies, it is possible to distinguish three different techniques and their use depends on the distinguished wavelength of the emitted light. 1. Near-infrared spectroscopy (NIRS) is a noninvasive functional technique that employs scattered light in the near-infrared spectral band to investigate the hemodynamic activity of a given body district and its associated functional capacity. It is usually used in the field of neuroimaging, but in recent years it has been exploited also in the field of wound care. NIRS allows the quantification of chromophores concentrations as a result of absorption and scattering phenomena related to scattered light in the nearinfrared electromagnetic spectrum (wavelengths between 700 nm and 1 mm). In this case, the chromophores of interest are represented by the contributions of oxygenated and deoxygenated hemoglobin at the most superficial areas of the cerebral cortex. In fact, the absorption coefficient of water (the main constituent of biological tissues) within this spectral band is negligible compared to those for hemoglobin. Therefore, measuring differences in the absorption spectrum over time makes it possible to attribute almost entirely measured changes in light intensity to respective changes in hemo-

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globin concentration. ­ Conventionally, at least two different wavelengths are used, one above and one below the isosbestic point between oxygenated and deoxygenated hemoglobin within the near-infrared spectral band; however, it is possible, both theoretically and experimentally, to employ multiple wavelengths in order to achieve better discrimination of the concentrations thus measured or, likewise, to investigate the trend of additional chromophores [24]. 2. Ultraviolet radiation for bacterial fluorescence is a technique that exploits low intensity UV light (between 315 nm and 400 nm) in order to trigger the fluorescence phenomena of certain bacterial strains that can proliferate in the wound bed. In [25], it describes a new generation device (the MolecuLight™) which exploits this phenomenon and has shown the ability of obtaining high-standard results with bacterial detection and differentiation in wounds. These device implements a Wood’s lamp or black light which is a light source that emits electromagnetic radiation mainly in the UVA range and to a negligible extent in the visible light range. The Wood’s tube lamp, unlike ordinary fluorescent tubes, does not employ phosphor in the inner surface of the tube, but filters the ultraviolet emission of the gas by means of a Wood’s filter transmitting only the radiation in the UVA range. 3. Thermography is a noninvasive and nondestructive analysis technique that relies on IR (8–14 μm) image acquisition. The use of thermography allows the reading of radiation emitted in the infrared band by bodies subjected to thermal stress. Radiant energy is a function of the surface temperature of materials, which in turn is conditioned by thermal conductivity and specific heat, which express in quantitative terms the ability of the material itself to transmit heat or retain it: a material with high values of conductivity will heat quickly and just as quickly cool. An IR thermographic system consists of a camera connected to an image processing and recording system. The IR detectors are responsible for detecting the consistency of the radiation that

strikes them and for analyzing the radiating surface point by point to arrive at the definition of the heat map. Recently, this technique has been used in wound care in order to analyze the state of infection of inflammation of wounds, mostly on burns [26, 27].

30.2.2 Overview of Nonoptical Imaging Techniques in Wound Care As mentioned in Sect. 30.2, there is a class of technologies that incorporate the nonoptical imaging techniques. These differently from the optical imaging devices (described in Sect. 30.2.1) do not measure the intensity of a transmitted, refracted, or reflected light beam, but elaborate an image that comes from data gathered from the results of other chemical and physical phenomena. In last years, many different techniques, technologies, and devices that can be included in this field have been developed and brought to the market. Their main advantage is that by sensing physical phenomena and chemical reactions that are not associated with the emission of photons, these solutions render possible the elaboration of images given by a variety of different physiological factors that otherwise would not be able to analyze. In the field of wound care, two of these are the most relevant since they are used in order to detect mostly inflammatory pathways and hemodynamics and these are the ultrasonography and the magnetic resonance imaging (MRI). 1. Ultrasonography or more simply eco-­ Doppler (or rarely Doppler sonography) is a noninvasive therefore easily repeatable technique used in medicine to study the anatomical and functional status of blood vessels, arterial and venous, and the heart in real time and simultaneously (duplex scanner). It takes its name from its physical principle of operation, the Doppler effect. Used for more than three decades, it has considerable value in both diagnostic, prognostic, and therapeutic fields in cardiac and vascular disorders which

30  Imaging and Measurement


are one of the main causes of chronic wounds color persistence, or it is used to better [28]. With the use of ultrasonography, through visualize the internal vasculature of an B-mode images, the morphology of the walls, organ (liver, kidney, thyroid, spleen). their motility, the presence or absence of (c) Doppler flowmetry allows us to analyze endoluminal formations, and the structure of the flow pattern within vessels and thus the “atherosclerotic plaque” are studied, while highlight stenoses or closures. with pulsed Doppler, the hemodynamic situa- 2. MRI is an imaging technique used mainly for tion of the blood flow at that particular point is diagnostic purposes in the medical field, assessed through spectral analysis and the based on the physical principle of nuclear degree of purity of the sound, and thus, the magnetic resonance. The adjective “nuclear” various degrees of stenosis can be quantified, refers to the fact that the density signal in MRI distinguishing hemodynamically significant is given by the atomic nucleus of the element from non-hemodynamically significant stenobeing examined, whereas, in more widespread ses. The morphological characteristics of athradiological imaging techniques, X-ray denerosclerotic plaques can also be assessed, sity is determined by the characteristics of the based on their echogenic features. This methelectronic orbitals of the atoms hit by X-rays. odology is currently being supplemented with MRI is not harmful to the patient, and the blood flow staining for even more precise patient is not subjected to ionizing radiation information on blood flow. The exploitation as in the case of techniques making use of of the Doppler effect in ultrasonography can X-rays or radioactive isotopes. The informahave different characterizations, all used in tion given by MRI images is essentially of a the assessment of the vascular structure of the different nature than that given by other imaggiven body region. Among the most coming methods: In fact, discrimination between monly used we can find: tissues on the basis of their biochemical com (a) Color Doppler is indicated for the study position is possible. The principle of operaof vascular structures. In fact, thanks to tion is based on subjecting the patient to a the coloring performed by computer, the strong static magnetic field. The magnetic movement and direction of blood flow field strength can range from tenths of a tesla, can be studied. The principle is based on for small machines dedicated to the study of the real-time association of a two-­ joints, and up to 3 T for machines currently on dimensional ultrasound image with a the market for diagnostic purposes. The pulsed Doppler signal. Conventionally, importance of this examination lies in the fact red color is attributed to structures that it is possible to discriminate, for example, approaching the probe and blue for those between a liver tissue and a spleen tissue receding. The method has revolutionized (which with respect to X-rays have the same the diagnosis of vascular and cardiac distransparency), or healthy tissues from lesions, eases with the ability to detect and monigiven to the different relaxation times of the tor arterial and venous stenosis, molecules of the different tissues when exitaneurysms, deep venous thrombosis, and ing the spin given by the magnetic field of the chronic venous insufficiency over time. device. (b) Power Doppler is similar to color Doppler, but it measures the frequency energy of the structures being examined. 30.3 Wound Measurement This gives a more sensitive signal but no Techniques information about the direction of motion of these structures. It is applied when a “Good measurement derives from good samcomplex parietal lesion, such as an ulcer- pling” and “You can’t manage what you can’t ated plaque, is to be observed with greater measure” are the two main aphorisms that are


taught to students that enter the world of measurement, also known as metrology. Every expert in this field would state that both sayings are true. In wound care, measurement is still an area where a dominant standardized model is not yet consensually accepted by its key opinion leaders. This is due to the facts that are described in Sect. 30.1: There are too many variables to take into consideration in order to perform a precise assessment of a wound that ranges from its chemical to its morphological proprieties. There are some, though, that have to be taken into account. Historically speaking, wound assessment has always been performed primarily by the correct evaluation of its physical size through time. King Henry VIII Tudor of England (1491–1547) is also known for having suffered of a cutaneous ulcer in the right leg, which started after an injury during a hunting party. Nowadays, analyzing the historical evidence, we are able to state with certainty that his wound that seemed to be acute and traumatic has never healed since he suffered from Cushing’s syndrome. In any case, it is textually reported in the Encyclopaedia Britannica [29] that “[...] To soothe His Majesty’s pains the most learned physicians in the World were called in. [...] Assessing the extent of the wounds, new bandages were applied, but without being able to heal him completely [...]”. Though the methods that were used at the time to cure the King were essentially bloodletting, wraps with soothing herbs and removal of necrotic tissue, it is clear that the most comprehensible variable for his surgeons was the wound size. Secondly, different studies [16, 17] that state that the morphology of the wound is at least one of the key indicators of good healing process. Moreover, it is a fact that wound size measurement is one of the quickest and easiest ways to understand its clinical state, taking into account the means of imaging (data collection) described in Sects. 30.2.1 and 30.2.2. Taking into account the everyday good clinical practice, it is clear that the primary need of wound care specialists is to be equipped with tools that can help them render a good, quick, and precise wound assessment. Considering the features and capabilities of the technologies described in the previous sections of this chapter,

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the following discussion will be centered on the available techniques of wound measurement (i.e., optical imaging techniques) since it has been clinically proven that in this field are the most reliable, the most portable, and the most integrable in the normal wound care clinical procedures. Before parting with the description of the measurement means in the field of wound care, it is necessary to answer a fundamental question: What does measurement mean? In the mathematical, physical, and natural sciences, measurement is the assignment of a range of values (measure) to a particular physical property or chemical property called a measurand, defined through a physical or chemical quantity. Measurement is thus the process carried out to assign a measure, although in common parlance it is customary to use the term measure instead of measurand and presupposes the existence of a system of measurement. The term measurand does not refer to the object or phenomenon on which a measurement is being made, but to a specific quantity that characterizes them: For example, when we measure the temperature of a liquid, the measurand is not the liquid, but its temperature. Lord Kelvin, the famous physicist from which the International Standard gave the name to the universal unit of measurement of temperature, stated in 1883 “When you can measure what you are speaking about and express it in numbers you know something about it; but when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind.” Due to experimental and theoretical issues, the measurand is not, in reality, describable by a single numerical value, even assuming infinite measurement precision. Each measurement is thus defined as an interval of values within which it is likely to lie. The width of this range defines its precision: The larger the range, the lower the precision associated with the measurement. The development of metrology has led to definitions in statistical terms of the definition of measurands and to the introduction of the concept of measurement uncertainty. The latter, to a first approximation, can be defined as the width of the range of values: The larger the range, the greater the measurement uncertainty. In the

30  Imaging and Measurement

most common case, uncertainty is defined as the statistical distribution of a (virtually) infinite sample of measurements made on the measurand. The interval is associated with a numerical value identified with the mean of the measurements. Therefore, in metrology, a measurement is always defined with three components: 1. The numerical value. 2. The unit of measurement of the quantity, or the scale of the property. 3. The uncertainty associated with the measurement. The study of measurement and the understanding of standardized measurement system (i.e., metrology) is not new, and it is possible to extract its arbors from ancient times. With the French Revolution came a turning point: The metric system was born. Various thrusts from the world at that time led the constituent assembly to adopt a new system based on the meter, that is, based on a natural magnitude, the 40,000,000th part of the earth’s meridian. The platinum–iridium bar used as a sample of the meter from 1889 to 1960 (shown in Fig.  30.4a). From 1875 to 1889, the International Bureau of Weights and Measures made and distributed some 30 samples of the meter and kilogram. The metal chosen was an alloy of platinum with 10% iridium, refractory

Fig. 30.4 (a) Bar n. 27 that served as reference of the meter from 1889 until 1960. (b) The bar k. 4 that still serves as reference of the kilogram



metals that had not yet been manipulated in such quantities and whose purity and homogeneity were required to be very high for the time. Since then, the science of measurement, metrology, has made great strides, creating systems (including the SI) that have enriched and simplified the metric system, hand in hand with the evolution of science and technology. In other words measuring something parts, under a theoretic point of view, from the comparison of the measurand with a well-known reference. In Fig.  30.4 are shown both the bar n. 27 and the bar k. 4 that have served as reference of distance and weight measurements. Centering the discussion on wound care, EDIs (see Sect. 30.2.1 for further explanation of these systems) exploit three different techniques of wound measurement that are summarized hereafter and in Fig.  30.5: analog, digital, and the new neuromorphic. According to what has been just stated, each method implies one or more types of measurements errors. As in any other field of study, the best method to use is not only given by the absolute entity of the error, but also how the entity of the error effects the consequences of the measurement. In other words, the wound care specialists should ask themselves: “Is the measurement error of the method that I’m using leading to a clinically relevant outcome?”



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Fig. 30.5  Three different kinds of measurement techniques implied in wound care. In the figure are reported the different kinds of errors that these methods led to and that have to be taken into account in a diagnostic decision.

Although some errors might be the same for different techniques, their entity varies due to the technologies and the methodologies that are exploited when choosing one technique with respect to the other

30.3.1 Analog and Digital Measurement Methods

wound’s depth and volume. Though these techniques are becoming more and more popular, there is still a large number of specialists who uses analog measurement techniques that in some cases present a high degree of empiricality. Analog measurements in wound care were and are still usually performed with simple rulers for the calculation of the wound surface and with cotton swabs inserted in the wound bed in order to obtain a rough evaluation of the lesion’s depth. This technique presents several problems. First of all, it can be painful for the patient: The insertion of an object inside the wound bed or the simple touch of a ruler with the damaged skin can cause a high degree of discomfort. In this case, different discomforts are felt by both the patient and the operator, since the later has to perform an objective measurement, while the patient is moving in pain consequently increasing the degree of approximation of the measurement. Secondly, when measurements are taken by hand, the returned values have to be transferred to a clinical folder or a report that can be on paper or digital, increasing both the time consumption of the visit and the risk of losing the acquired data. Lastly, wounds have an irregular shape and their size is

The difference between analog and digital techniques of measurement basically resides in who is actually performing the comparison between the measurand and the measurement reference. Analog measurement implies a direct comparison between the two, and this is performed directly by the operator; one example can be the measurement of a line with the use of a ruler. In digital measurement, the comparison is performed by a dedicated device that acquires the information of the measurand and through fixed mathematical rules returns a number that should be equal to the entity that is to be measured. In the last ten years, the first EDIs hit the market and have been tested in standard clinical procedures regarding wound assessment and monitoring. These devices present different functionalities and perform measurements exploiting different techniques. The one thing in common is that they have all been designed to (also) perform morphological measurements of the wound. In some cases, these measurements are only bidimensional; in other cases, the solutions are able to measure the

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very difficult to calculate by hand without the aid of a computational mean, especially if it is measured with a linear ruler. Many operators try to go around the problem by “framing” the wound inside a regular shape such as a rectangle or a square and take the surface of the encircling shape as the wound’s area. This incorrect approximation error can lead to measurement inconsistencies that can be up to 30% as shown in the example in Fig. 30.6. Digital measurements in wound care are usually performed though EDIs that are devices that in the majority of the cases implement a CMOS camera in order to take the picture of the lesion and distance sensors (see Sect. 30.2.1 for further details on these devices). By taking a picture of the wound through the digital camera, the image is automatically discretized in a number of regular pixels given by the camera’s intrinsic resolution (the resolution depends on the camera’s sensor). By reading the distance of the camera from the plane on which the wound lays through the distance sensors, it is easy to understand the size of the physical area depicted by each pixel in the picture. The operator then, though the device’s screen or through other methods of interaction with the device, digitally traces the wound’s perimeter and the EDI easily calculates the wound’s surface. In some cases, the EDIs do not have distance sensors that can read the distance between the device and the wound, and so, other techniques are implied in order to have a correct match between the pixel and the size of the area that they depict. One simple technique that is

Fig. 30.6  A generic wound framed inside a rectangle. Due to the irregularity of the wound’s shape, the area of the rectangle and the area of the wound can have up to a 30% difference


used by different producers is the so-called blue dot technique. This procedure implies that the operator lays a physical reference (usually a sticker) that has a known color, size, and shape in the field of the image. The picture is taken with the device that recognizes the sticker thanks to its color and automatically calculates the number of pixels in the resulting image that shows it. Since the EDI has in its memory the actual size of the sticker, it can easily calculate the depicted area by each element. The rest of the procedure is the same as in the other EDIs: After tracing the actual contour of the wound in the image, the device counts the pixels and easily arrives to calculate its surface. There are different devices in the market that have been widely clinically validated which use the blue dot technique. The most common and well-known is the MolecuLight™, and its clinical study is reported in the work by Kleitjes et al. The blue dot technique offers also the possibility to implement measuring functionalities to devices without the use of added sensors (a part from the CMOS camera): This implies the development of mobile applications that can be installed on personal devices such as smartphones and tablets. One of the latest is represented by Imito™, an all-around smartphone application for ulcer management [30]. Imito, in particular, uses its token also as a color reference in order to easily discretize the tissues composing the analyzed wound bed. EDIs that perform a digital measurement of the wound have several advantages over the analog methods. First of all, the measurements are for sure more precise due to the possibility by the operator to easily calculate an irregular shape lake the ones of wounds. Secondly, EDIs are noninvasive devices; for this reason, the patient’s experience and quality of life during the assessments increase sensibly. In many cases though, both methods of measurement present several errors that can be due both by the operator and by the intrinsic characteristics of the devices as reported in Figure The same errors are briefly explained hereafter and in Table 30.1 are reported the mean entities of each measurement error for each measurement technique.

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Table 30.1  Comparison of the error entities with respect to the measurement techniques. These values have been calculated on average size wounds (between 1 cm2 and 10 cm2). The values reported in the table are the maximum expected errors on the total measurement Measurement technique Analog meas. Digital meas.

Positioning error Up to 20% Up to 10%

1. Positioning Error: This inconsistency occurs when the measurement device is not physically paced correctly on the measurand. This might happen when using a ruler and the reference tick does not coincide precisely with one of the ends of a wound. When using and EDI, this might occur when the picture of the wound is not taken precisely parallel to the wound’s plane. 2. Instrumental Error: No measuring device is 100% precise. There always are some inconsistencies between the real physical entity and the device’s actual scaling. Usually the entity of this error is reported by the producer, and in case of the EDIs is very low. In EDIs, this error is usually negligible. 3. Reading Error: This kind of error strongly depends on the operator when using an analog measurement technique. Even if the ruler is precisely placed with respect to the measurand, the reading can be subject to the position of the operator with respect to the ruler when performing the measurement. To help understanding this phenomenon, it is necessary to think of the reference tick of the same ruler. Each tick reports a distance from its previous one and the one after, but also the ticks have their own dimension such as a width. Depending whether the initial reference is taken from the beginning of the tick or at its end, the measure can change. This error is higher when the measurand has a dimension similar to the basic scaling of the ruler (i.e., when measuring entities that are less than one centimeter when using a normal linear ruler). 4. Continuous Reading Error: This kind of error refers to only digital measurement techniques. As mentioned before, a CMOS camera discretizes an image in a regular grid of pixels, and in an EDI, the operator must trace the perimeter of the wound on a screen. The

Instrumental error Up to 10% Up to 1%

(Continuous) reading error Up to 50% Up to 5%

tip of the operator finger or the cursor of a mouse or the tip of a pen usually has a size that is larger than the single pixel, and for this reason, some inconsistencies in the total measurement can occur. As for the reading error in analog techniques, this error decreases exponentially with the increase of the total size of the measurand.

30.3.2 Neuromorphic Solutions in Wound Care In the last few years, this new class of EDIs has proven its efficacy in the field of wound care for their high precision of measurement and of classification. Neuromorphic EDIs differ from the rest of the devices since they implement artificial intelligence algorithms that are able to analyze clinical images and automatically identify and classify the wound with respect to several clinical classification scores. Neuromorphic engineering (also called neuromorphic computing) is a concept that started at the beginning of the nineteen-seventies that had the scope to develop systems, both software and hardware, able to analyze large amounts of data mimicking the biological–neural architectures of the brain [31]. One of its branches is devoted to develope what are known artificial intelligence (AI) algorithms that are computational methods able to solve complex problems with large amounts of data. In the years, many different types of AI algorithms have been developed and used in different fields, but among the most commonly used we can find the artificial neural networks (ANNs) and their derivatives. ANNs are the computational structures that have to be designed in order to solve a given problem (i.e., classification, statistical inference). Their particular structure implements two basic elements that

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can be arranged accordingly to the given problem that has to be solved: 1. Nodes: These are the basic computational structures of the network and symbolize the input, transfer, and output data. They should work as biological neurons. 2. Links: The links, as the name suggests, represent the mathematical relations between two or more nodes. These elements simulate biological synapse. As in the biological brain, ANNs do not change their initial structure, but change the values associated with the different links and nodes that work as mathematical operators with which the input data are treated. Indeed, ANNs and in general AI algorithms vary from normal computational routines due to their evolution dynamics. In other words, while in classic informatics algorithms are coded in order to perform a predetermined sequence of actions on the data, AI algorithms are instead trained. Training a net-

Fig. 30.7  A “normal” training procedure of an AI algorithm. At first, the network is designed and coded. Then, a vector of examples (i.e., a group of initial data) is presented to the network as input. Then, the network evolves: its nodes and its links change their internal values in order to sort and analyze the data as required by the developer.


work means presenting an input set of data, and the elements of its structure change their internal values in order to treat the data according to the problem that has to be solved; this phenomenon is also known as machine learning (ML). An example of a general training process of an AI algorithm is represented in Fig. 30.7. Training the network, under an operational point of view, means extracting the features from the data that have to be analyzed. These features can vary, but in general they can be described as the characteristics that unite different groups of data for classification and correlation purposes. Due to their intrinsic proprieties, neuromorphic EDIs present several advantages with respect to the classic devices. First of all, measurement errors that are due to human factor are depleted: Neuromorphic EDIs, if well trained, are able to analyze images and distinguish automatically the desired objects. For this reason, the segmentation of wounds in the images taken by the device reaches the highest precision possible. Moreover, these devices are able to perform other analysis

Afterward, there is execution of the algorithm, where its computational efficiency is tested. If the results from the execution do not meet the required standards, other training sessions are performed until the optimal efficiency is reached


on the data, for instance, as they are capable to distinguish and segment a wound; they are also able to distinguish the different tissues that compose the wound bed and so able to perform a clinical classification of the lesion with respect to validated standards such as the WBP score. As all means of measurement though, these devices are still affected by two types of measurement errors:

J. Secco

a dedicated front end through a capacitive touchscreen display (Fig. 30.8). The ulcer analysis algorithm implemented in WV applies a discrete time cellular nonlinear network (DT-CNN) computing architecture in order to identify the wound, hence providing relevant measurements of its area, depth, and volume [33–35]. Those acquired measurements include the wound area expressed in squared cen 1. Instrumental Error: These devices suffer as timeters, the wound depth expressed in millimeall other EDIs suffer from the instrumental ters, and the wound granulation expressed errors given by the measurement components through the WBP score. DT-CNN is a parallel that they implement (e.g., any distance sensor computing paradigm, introduced by Chua and that is used to dimension the pixels that depict Itoh [36], similar to artificial neural networks for the wound through the distance of the device processing any dimensional signals. As any other from the lesion’s plane). bio-inspired neuromorphic algorithm, the 2. Interface Error: This error occurs during the DT-CNN goes through a learning phase and an training procedure of the algorithm. Its com- inference phase. The cellular nonlinear network putational efficiency (i.e., its actual capability in the WV algorithm, which processes a two-­ to correctly analyze the data, such as an dimensional color image, in the former phase is image) is given by the quality and the amount provided with statistical information about the of data used for the training of its algorithms. tissue forming the wound bed through a color If in such data there are mistakes, or it is lack- analysis. Those statistics are extracted from the ing intrinsic information, the algorithm will training set by a digital segmentation of wound erroneously learn the mistake or be imprecise areas in the images contained in the training set in its outputs. (more than 1500 wound pictures). The resulting statistical information takes the form of a mapOne of the newest devices that has been ping, hereafter named g (·), or in other words an recently clinically validated and is entering the ℝ3 function, between each of the 16,777,216 posgood clinical practice in wound assessment is the sible 24bit in the RGB color space [23]. Wound Viewer (WV), developed by Omnidermal The nonlinear processing units making up Biomedics (Italy) [32]. The WV is a skin wound DT-CNNs are often referred to as neurons or assessment tool designed to measure and collect cells. Those cells can be implemented, depending data regarding patients and their wounds. The on the underlying technology, as arbitrary indedevice is noninvasive, does not come into contact pendently computing units; this results in a very with applied and accessible parts, and can be fast parallel algorithm to run. When using a used for both ward and home visits. The device DT-CNN to perform an analysis of an image, like and the related software are to be considered as in the case of the WV algorithm, each cell of the an adjunct tool for wound care management that DC-CNN corresponds to a pixel of the digital is not intended for diagnostic purposes. This picture. Under a mathematical point of view, let I device was designed to run the proprietary artifi- be the two-dimensional RGB color image and O cial intelligence algorithm for wound measure- the computed black and white image underlying ment and assessment. The device is equipped the wound area (both having dimensions W × H, with a 5MP color CMOS camera sensor to Θ (·) be the Heaviside function and N an even acquire high-resolution pictures, 16 high-­ integer number. By appropriately setting the precision IR distance sensors, and 4 white LEDs. parameters θ and ρ, which are the cell’s and the Users are supposed to control the device through automata threshold levels, respectively, the image

30  Imaging and Measurement Fig. 30.8  WV device shown in its (a) top and (b) bottom view. The figure highlights its main elements such as the type-C IR sensor, the CMOS camera, the white LEDs, and the capacitive touchscreen




O can be computed by applying the formula in Equation 30.1, where (i, j) are the coordinates of a single pixel and Ii, j is the pixel RGB triplet code, while Oi, j is the pixel of the binary output image:   i + N2 j + N2  Oi , j = Θ  ∑ ∑ Θ g ( I i , j ) − θ − ρ  ,  h =1 w =1   





0 ≤ i ≤ H − 1  0 ≤ j ≤ W − 1.

As an example, the elaboration result of the wound is given in Fig. 30.9. The original image in (Fig. 30.9a) went firstly through a preprocessing phase and then presented to the trained DT-CNN.  Each automata part of the network,

using the statistical chromatic knowledge stored in g (·). Then, the output Oi, j was computed by counting the number of pixels in a given proximity (N + 1) of the input element Ii, j whose color appeared enough times (more than θ) in the wounds from the training set. The total number of pixels verified to be characteristic of a wound area is then compared to the threshold level ρ. If this critical value is lower than the weighted counted number of pixels, then the pixel Oi, j is reported to be part of a wound area (set to binary true, white in (Fig. 30.9b)), else it is rejected. Regarding the wound classification, the algorithm takes solely into account the pixels that were recognized as part of the wound (i.e., white elements in Fig. 30.9b). Once the whole surface of the wound is recognized, the highlighted elements are analyzed regarding their color scheme (RGB). The whole set of possibilities regarding the color of pixels forming the wound has been

J. Secco




Fig. 30.9 (a) Example of a wound image before being analyzed by the WV device’s algorithm. (b) Resulting binary image where it is possible to note that the edges of

the wound coincide with the borders of the binary mask given by the discrete time cellular nonlinear network (DT-CNN)

classified into four macrogroups: red, white, black, and yellow. The wound images in the training set have been classified through the WBP score (in granulation) and then matched taking into account the presence of the four macrogroups in the wound area. Through this training phase, the algorithm is able to analyze these color schemes and perform an automatic classification.

The study rationale parted from the fact that skin ulcers are treated with continuous and periodic dressings that are carried out by the specialist in charge. During a normal a normal assessment, the wound care specialist manually or with the help of an EDI measures the extent of the wound and applies a new dressing. As mentioned in Sect. 30.3, one of the main characteristics that are taken into account is the differences in the morphology of the lesion between two different assessments. Another variable that is usually taken into account is the wound bed and its composition, and a classification through a standard clinical scale (as the WBP) is performed. The standard EDIs can result in being time-­ consuming and less intuitive since there is no process of automatic analysis of the wound, on top of the fact that the operator actively participates in the wound measurement increasing the risk of errors. The purpose of the trial was therefore to verify the ease of use of WV in a normal wound assessment session, comparing its results with the other three EDIs. Regarding the wound bed, its correct classification is taken into account as a critical variable since it can be taken as a guide for therapeutic decisions. Before neuromorphic EDIs, such as WV, wound classification was the only prerogative of the specialists, and depending on the degree of its clinical experi-

30.3.3 Clinical and Economical Advantages Resulting from the Use of Neuromorphic EDIs In this Section neuromorphic EDIs have been described with respect to the previous generation of the same device class, describing its advantages in terms of measurement precision and classification capabilities. In particular, the WV device has been taken as an example for two reasons: first to provide a better understanding of the analysis that these kinds of devices perform in a wound assessment session and second because it underwent a clinical trial that proved its measurement efficiency as well as its ability to be integrated in the common good clinical practice described in [23].

30  Imaging and Measurement

ence, this can result in being subjective and difficult to standardize. WV and this class of devices aim to overcome the subjectivity inherent in the system through automatic evaluation through its AI algorithms. In details, the aim of the trial was to verify that the WV is able to automatically identify the wound in the image and perform a correct measurement and classification of the lesion, suitable for providing high standards of cure. The clinical trial has been performed at the Department of General Surgery at the Azienda Ospedaliera Universitaria San Luigi Gonzaga (Orbassano, Italy—protocol number OC15194). It has been conducted on 150 patients divided into three cohorts of 50 patients each according to the type of wound: lower limb ulcer, diabetic foot ulcer, and pressure ulcer. Once the patients were enrolled in the study and gave their informed consent to participate in the trial, their wound were measured with WV and with other three classic EDIs, whose measurement capabilities are universally known as precise. At the same time, the operator classified the wound through the WBP score in granulation and then compared its classification with the one returned automatically with WV and the one that resulted from the


Fig. 30.10 (a) Distribution and comparison of the morphological measurements performed by WV with respect to the other EDIs. (b) Comparison of the wound classifi-


classification of the wound bed tissues made by one of the another three EDIs. The measurement distribution of the patient population was compared through inferential statistical analysis in order to verify the similarity of the results obtained from all the devices used in the trial. Through a Kruskal–Wallis one-way ANOVA analysis, a p ‐ value = 0.9 proving that the distributions were in fact the same and therefore the automatic measurements of the WV could be considered precise (Fig. 30.10a). In addition in all the cases the WV device was able to correcly classify the assesd wounds with respect to the visual assessment of the physician performing the assessment and differently form the compared EDI whose classification capability proved to be unsatisfactory for clinical standards (Fig. 30.10b). The WV has proven in the years to be effectively integrable in the everyday clinical practice, not only inward, but also in telemedicine procedures. In many places of the world, and most importantly, after the COVID-19 pandemic, the capability to monitor a patient while at home instead of hospitalizing him has become more and more crucial. Telemedicine in wound care though presents different issues. First of all, the caregivers (i.e., physicians and nurses) that treat


cations (using the WBP in granulation) performed by the WV with ones performed by the physician and the employed EDI for this particular scope

J. Secco


the single patient may vary over time leading to inconsistencies in the therapeutic plans, in the prescriptions, and in the clinical assessments. These inconsistencies, a part from the fact that they can worsen the quality of life of the patients, consequently lead to a reduction in the cost-­ effectiveness of the various cures. The lack of a standardized mean of wound assessment and the incapability of the hospitals to centrally monitor the situation of their patients has become one of the major pains. In a hospital in Italy, the WV was uptaken for this specific reason and the data regarding the cost of cures between the year before the use of the technology and the following were compared (Fig. 30.11). It must be noted that the total cost is divided into three major expenditures that are the medication costs (i.e., the cost of the prescribed dressings, the visit costs (i.e., the cost of the single specialist traveling through the territory to perform a medication), and the cost for the therapeutic plan (i.e., the administrative costs for medical prescription). Surprisingly, thanks to the use of WV and its capability transmit, the information among the operators directly into the patient’s electronic medical record (EMR), the wound care specialists were able to administer the right therapy to the single patients according to their general clin-

Fig. 30.11  Reduction in the cost of cure (total and per single patient) in telemedical procedures regarding patients with chronic wounds. The values reported in the figure are in Euros [=C]

ical state. Moreover, it was possible to render efficiently the general operations regarding the patient management, concentrating the operators on the patients that required greater treatment and attention, lowering the number of visits to the ones that were going through a correct healing process. From these logical actions taken by the hospital through the use of his neuromorphic EDI, the total cost reduction for the hospital (with a population of around 850 patients per year) has reduced by 9%, while the cost of cure per single patient has reduced by 14%.

30.4 Conclusions Telemedicine is currently at the forefront of integrative technology with the goal of improving clinical care while reducing costs in all medical fields, such as wound care. In this chapter, an excursus of the most employed technologies in wound care has been presented and described. Many of the devices and techniques that have been reported were not available until ten years, others even less. These last years, under a technological development point of view, have proven to be the most interesting in this field, thanks to the effort of many researchers, clinicians, and companies that work with the sole goal to provide devices for accurate wound assessment. But the work is not yet done: Many more advancements in the field of imaging and measurement in wound care will come in the future years. This is mostly due to the fact the COVID-19 pandemic has shown the world that these kinds of devices can have a great positive impact on clinical practice. The last class of devices presented is the neuromorphic EDIs: These represent the most recent advancement in this particular field, and with the example given by the WV device, their efficacy is clearly proven. Acknowledgements  The author would like to thank the whole editorial board of this book. A special thanks is reserved Dr. Elia Ricci for this opportunity and his everlasting mentorship and cooperation in the author’s research work.

30  Imaging and Measurement



16. Khoo R, Jansen S. The evolving field of wound measurement techniques: a literature review. Wounds. 2016;28(6):175–81. 1. Vickers NJ.  Animal communication: when i’m 17. Haghpanah S, Bogie K, Wang X, Banks PG, Ho calling you, will you answer too? Curr Biol. CH.  Reliability of electronic versus manual wound 2017;27(14):R713–5. measurement techniques. Arch Phys Med Rehabil. 2. Graves N, Zheng H. The prevalence and incidence of 2006;87(10):1396–402. chronic wounds: a literature review. Wound Pract Res. 18. Falanga V. Classifications for wound bed preparation 2014;22(1):4. and stimulation of chronic wounds. Wound Repair 3. Tuttle KR, Bakris GL, Toto RD, McGill JB, Hu Regen. 2000;8(5):347–52. K, Anderson PW.  The effect of ruboxistaurin on 19. Albert H. A survey of optical imaging techniques for nephropathy in type 2 diabetes. Diabetes Care. assessing wound healing. Int J Intell Control Syst. 2005;28(11):2686–90. 2012;17:79–85. 4. Ferreira MC, Tuma Junior P, Carvalho VF, Kamamoto 20. Roobottom C, Mitchell G, Morgan-Hughes F. Feridas complexas. Clinics. 2006;61(6):571–8. G.  Radiation-reduction strategies in cardiac com5. Hersh WR, Hickam DH, Severance SM, Dana TL, puted tomographic angiography. Clin Radiol. Krages KP, Helfand M.  Diagnosis, access and out2010;65(11):859–67. comes: update of a systematic review of telemedicine 21. Duane W. Proceedings of the American physical sociservices. J Telemed Telecare. 2006;12(2 suppl):3–31. ety. On X-ray wave-lengths. Phys Rev. 1915;6:166. 6. Berkowitz L, Vyas S, Korolev IO, De Raeve P, 22. Kieser DC, Hammond C. Leading wound care techDorairaj P, Pillon S, Sakumoto M, Vasiliu-Feltes I, nology: The Aranz medical silhouette. Adv Skin Ashall-Payne L, Parker MB, et al. Predictions for teleWound Care. 2011;24(2):68–70. health in 2021: we can’t wait for it! Telehealth Med 23. Zoppo G, Marrone F, Pittarello M, Farina M, Uberti Today. 2021;6(1):1. A, Demarchi D, Secco J, Corinto F, Ricci E. Ai tech7. Bekara F, Vitse J, Fluieraru S, Masson R, De Runz A, nology for remote clinical assessment and monitorGeorgescu V, Bressy G, Labbe JL, Chaput B, Herlin ing. J Wound Care. 2020;29(12):692–706. C. New techniques for wound management: a system24. Fantini S, Frederick B, Sassaroli A.  Perspective: atic review of their role in the management of chronic prospects of non-invasive sensing of the human wounds. Arch Plast Surg. 2018;45(02):102–10. brain with diffuse optical imaging. Apl Photonics. 8. Wang C, Shirzaei Sani E, Gao W. Wearable bioelec2018;3(11):110901. tronics for chronic wound management. Adv Funct 25. Kleintjes W, Kotzee E. Moleculight i: X: A new tool Mater. 2022;32(17):2111022. for wound infection diagnosis. South Afr J Plast 9. Talal AH, Sofikitou EM, Jaanimagi U, Zeremski M, Reconstr Aesthetic Surg Burn. 2019;2:68–71. Tobin JN, Markatou M.  A framework for patient-­ 26. 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Izzetti R, Oranges T, Janowska A, Gabriele M, Ferrando J, Lopez-Torrecilla J. Looking for compleGraziani F, Romanelli M. The ap- plication of ultra-­ mentary alternatives to ctcae for skin toxicity in high-­ frequency ultrasound in dermatology and radiotherapy: quantitative determinations. Clin Transl wound management. Int J Low Extrem Wounds. Oncol. 2014;16(10):892–7. 2020;19(4):334–40. 12. Gethin G, et  al. The significance of surface ph in 29. E.  Britannica et  al.. “Encyclopaedia Britannica,” chronic wounds. Wounds. 2007;3(3):52. 1993. 13. Flanagan M.  Wound measurement: can it help us 30. Biagioni RB, Carvalho BV, Manzioni R, Matielo MF, to monitor progression to healing? J Wound Care. Neto FCB, Sacilotto R.  Smartphone application for 2003;12(5):189–94. wound area measurement in clinical practice. J Vasc 14. Gorin DR, Cordts PR, LaMorte WW, Menzoian Surg Cases Innov Tech. 2021;7(2):258–61. JO. The influence of wound geometry on the measure31. Monroe D.  Neuromorphic computing gets ready for ment of wound healing rates in clinical trials. J Vasc the (really) big time. Commun ACM. 2014;57:13. Surg. 1996;23(3):524–8. 32. Farina M, Secco J. “Live demonstration: 3d wound 15. Cukjati D, Rebersek S, Miklavcic D.  A reliable detection & tracking system based on artificial intelmethod of determining wound healing rate. Med Biol ligence algorithm,” in 2017 IEEE biomedical circuits Eng Comput. 2001;39(2):263–71.

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Wound Measurement


Valentina Dini and Giammarco Granieri

31.1 Introduction Wound measurement is important in monitoring the healing process of chronic wounds and in evaluating the effect of treatment. Several tools are available to support the caregivers in absence of consensus on which tools should be used to implement wound care. The tools should be easy to use by practitioners; at the same time, the measurements acquired should be accurate and reliable and user friendly. The research is increasingly focusing on methods that allow wound analysis and provide reproducible quantitative indications through devices that integrate multiple imaging methods leading to multiparametric analysis of the lesions. Instrument miniaturization and portability are a key point in wound imaging research. These new techniques have many potential major advantages such as: standardization of wound measurements, objective data to evaluate therapeutic procedures and protocols, and sequential comparisons.

31.2 Clinical Wound Assessment In the context of a holistic approach, the assessment of wound bed, wound edge, and perilesional skin is fundamental in wound management. The V. Dini (*) · G. Granieri University of Pisa, Pisa, Italy

triangle of wound assessment has been introduced to develop an integrated assessment tool that focus on these three aspects of wound to enhance patient outcomes, improving early identification of patients at risk of ulcer development and a proper and prompt treatment [1]. Wound bed, wound edge, and perilesional skin could be considered as three axes of a triangle, each with a specific importance in wound assessment. The evaluation of wound bed includes the assessment of the type of tissue and exudate, the signs of infection or inflammation, leading to the granulation tissue promotion. At the wound edge, the main objective is to reduce the barrier to healing identifying rolled, thickened, undermining, macerated, or dehydrated edges. The periwound area damage contributes to delayed wound healing and can cause pain reducing the quality of life of patient. The assessment of perilesional skin highlights the presence of maceration, excoriation, dry skin, hyperkeratosis, and eczema. The framework can be used to guide health professionals when evaluating a wound, setting management goals, and selecting treatment options. It has been showed how a Spanish hospital introduced the framework in the diabetic foot ulcer care pathway used in the region [2]. The triangle of wound assessment is a new tool that improves the concept of wound bed preparation [3] and time beyond the wound edges. The wound assessment charts are easy to use and useful to collect all relevant areas and is based on recent ­anthropological

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



research [4] that has shown integration of the periwound area within wound assessment is important to the patient, the clinician, for healing and for patient outcomes.

31.3 Wound Size Analysis The measurement of wound area is one of the most relevant prognostic indexes. It has been demonstrated that a 40% reduction in ulcer area after 4 weeks is a good predictor of wound healing [5]. The accuracy, agreement, reliability, and feasibility of wound assessment methods are a central issue in wound management. The focus in the last few decades has been on two-dimensional (2D) methods to measure wound area, which can be divided into contact methods (manual and digital planimetry) and non-contact methods [6]. Three-dimensional (3D) methods for measuring wound volume allowed to evaluate all dimensions including depth. A 3D approach provides a more accurate evaluation of the biological changes and thus results in more relevant data than a simple two-dimensional approach. However, none of the newer methods appear to be used on a routine basis, possibly due in part to the absence of valid comparative studies.

31.4 Wound Surface Area Measurement 31.4.1 Two-Dimensional Contact Methods Simple Ruler Method The simple ruler method is inexpensive and easy to use, it consists of multiplying the greatest length and width of the wound to obtain the surface area. Different studies demonstrated that the traditional linear measurement has the least accuracy especially in irregular wounds. It has been reported a 29–43% overestimation by the simple ruler method compared with manual planimetry [7]. Some authors found that the simple ruler method overestimated the wound area by an average of 41% compared with digital planimetry [8].

V. Dini and G. Granieri

The wound area can be calculated using standard mathematical formulae assuming that most wounds are spherical or elliptical. The most common approach is the elliptical method, in which the area is calculated by multiplying 𝜋 (𝜋 = 3.14) by the shortest and longest radii of the wound. Kantor and Margolis found a strong positive correlation between area measurements using the ellipse formula compared with digital planimetry [9], but the correlation was lower for wounds larger than 40  cm2. Other authors proposed an area measurement using a new area formula 0.73 × L × W (L = length, W = width) based on a shape factor, which is an index of wound circularity between 0 and 1 (1 is a perfect circle). This method was found to be more accurate than the elliptical model when compared with digital planimetry [10].

31.4.2 Planimetric Measurement Planimetric measurements can be manual or electronic. In the manual method, a transparent film is placed on the lesions and the wound border is traced with a pen. The tracing is placed on a metric grid and wound area is determined by counting the number of squares in the grid covered by the traced area. In digital planimetry, the margin of the wound is retraced onto a tablet computer that performs the same calculations [11]. Planimetric methods consider the body curvature and are relatively easy to learn, accurate, and reliable. Digital planimetry is slightly more accurate and reliable than manual planimetry. Both methods involve contact with the wound increasing the risk of infection.

31.4.3 Stereophotogrammetry A stereographical camera linked to a computer captures an image of the wound. The image is downloaded to the computer, and the wound perimeter is simply traced by moving the cursor on the monitor. The computer software calculates wound size and volume. This is an accurate, non-­ contact method, which reduces the risk of wound

31  Wound Measurement

contamination, but it is also time-consuming and expensive [12]. The device lacks the ability to accurately identify the epithelial age of the wound and is operator dependent.


establish the exact size of the skin lesions in each spatial axis [19]. By implementing digital photography with special analysis software, it is possible to perform a qualitative and quantitative analysis of the wound bed and wound edges to convert even colour scales into reproducible 31.4.4 Digital Imaging qualitative-quantitative measures. It is possible to quantify necrosis, fibrin, rate of re-­ An image of the wound is captured and trans- epithelialization, or a particular type of infection, ferred to a computer. The margin of the wound is providing a kind of global overview of the wound traced using a pointing device and the software with reliable and reproducible results even over uses a scale near the wound on the photo to cal- time and for different ulcers [20]. The use of staculate the area. Some authors evaluated a hand- tistical models allows to predict the evolution of held device provided by a laser scanner designed chronic wounds by monitoring the trend over to measure wound surface area and depth [13]. time. Standardization of any imaging method is The system was found to be fast and easy to han- the best way to consent the reproducibility of the dle and had high intra- and inter-rater reliability measurement. for large wound rather than small ulcers [14]. A The digital imaging method is equally accuhandheld wound measurement device, based on rate and reliable compared to the planimetric smartphone technology, seems to be accurate at approach and is a non-contact method, eliminatdifferent distances and angles. Digital imaging is ing the risk of wound contamination [21]. Digital a non-contact method that is equally accurate and images can be affected by the illumination, locareliable as planimetric methods [15]. Digital tion, and size of the wound, and variations in images are the most cost-effective [16], non-­ camera angle can lead to underestimation of the invasive, and the easiest approach for high-­ wound area [22]. The method is also time-­ resolution wound recording and size measurement consuming from the instant the image of the [17]. However, it is also time-consuming and can wound is captured by the camera until the wound be affected by the illumination, location, and size area is estimated by the software. of the wound. The high resolution of modern digital images allows us to have an accurate analysis, not only 31.4.5 Wound Volume Measurement the lesion morphology, but also the acquisition of colour images, that provides a qualitative esti- Several 3D techniques for measuring wound volmate of the various types of tissue present in the ume have been proposed. MAVIS (Measurement lesion and in the peri-wound skin [18]. Due to its of Area and Volume Instrument System) is a non-­ reliability, the acquisition of digital photographs invasive method using color-coded structured has become the gold standard for testing new light. The camera provides a serial photo used in imaging methods. A disadvantage of this method, a mathematical algorithm resulting in a 3D reconespecially those performed with cheaper sys- struction of the wound. It has been described a tems, is the inability to assess lesion depth in 2D. 3D optical scanner based on structured light inteModern systems provide the depth parameter grated with a thermal imager able to measure by means of algorithms for RGB images pro- wound size and detect the inflammation [23]. cessed by image-processing algorithms (segmen- LifeViz® (QuantifiCare, San Mateo, CA) is a 3D tation, edge detection, colour processing, active system with a high inter-rater reliability for volcontour, and volumetric information), allowing ume measurements (ICC = 0.9867; P 100 mmHg ≥0.80 0.60–0.79 70–100 mmHg 0.40–0.59 50–70 mmHg < 50 mmHg ≤0.39 Clinical manifestation of infection No symptoms or signs of infection Infection present, as defined by the presence of at least two of the following items: – Local swelling or induration – Erythema >0.5 to ≤2 cm around the ulcer – Local tenderness or pain – Local warmth – Purulent discharge (thick, opaque to white, or sanguineous secretion) Local infection involving only the skin and the subcutaneous tissue (without involvement of deeper Tissues and without systemic signs as described below) Exclude other causes of an inflammatory response of the skin (e.g., trauma, gout, acute Charcot Neuro-osteoarthropathy, fracture, thrombosis, venous stasis) Local infection (as described above) with the signs of SIRS, as manifested by two or more of the Following: – Temperature > 38C or  90 beats/min – Respiratory rate > 20 breaths/min or Paco2 12,000 or  60 mmHg 40–59 mmHg 30–39 mmHg < 30 mmHg

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35  Infected Wound Bed Management: The Diabetic Foot

from limb revascularization. For these reasons, both the IWGDF and the Global Vascular Guidelines [11] suggest its use when characterizing DF lesions, particularly when infected or ischemic, as well as PAD related lesions. On the other hand, the main limit of the WIfI classification is that it does not separately consider the loss of protective sensation (LoPS), a main pathogenetic factor of DF lesions. Also, for each of the three critical parameters (Wound, Ischemia, and foot Infection), four possible grades exist and must be ascertained to provide a final WIfI score. In the past, several other classifications have been used to classify DF ulcers. Among all, it is important to mention some whose use may still be found in non-specialist settings. –– Wagner classification [12], divides DF lesions into five grades ranging from no lesions to extensive gangrene. Its use is however limited because it does not consider separately the presence/absence of ischemia and/or infection. –– University of Texas Classification [13], defines DF ulcers according to their depth, the absence/presence of ischemia and the absence/presence of infection. This classification scheme, when applied to DF patients, resulted to be quite predictive of overall amputation risk. However, its major limit was to consider ischemia and infection as a yes/no diagnosis. –– SINBAD classification [14], considers the ulcer Site, presence/absence of Ischemia, presence/absence of LOPS (Neuropathy), Bacterial infection, wound Area and Depth. It is a quite easy to use tool, as it does not require use of any specialist equipment. However, its simplicity’s drawback is a poor definition of the degree of ischemia and infection; thus resulting in limited use in facilitating patient care. Its use should be dedicated only for communications among health professionals to optimize referral [9] as suggested in the IWGDF guidelines.


35.1 Clinical Approach to the Diabetic Foot 35.1.1 The Multidisciplinary Diabetic Foot Team The Diabetic Foot syndrome is characterized by an extremely variable array of clinical presentations as well as clinico-pathological factors involved in its pathogenesis. As no single specialty could ever take over its management as a whole, the DF has been considered as the “Cinderella” among all diabetes complications. Furthermore, it has been associated with considerable healthcare costs, morbidity, and mortality. While for other diabetes complications affecting the eyes, kidneys, nerves, or heart, there are specialists (e.g., ophthalmologists, nephrologists, neurologists, and cardiologists) with skills to assume the entirety of their care, this is not the case for DF syndrome. Rather, the diabetic foot and its complications requires the care of a combination of multiple medical and surgical branches. For these reasons, it has been proposed by several guidelines, as well as by experts in the field, the multidisciplinary diabetic foot team (MDT) as the best clinical model to approach diabetic foot care [15–17]. According to this view, the vast complexity of DF lesions can be safely and effectively managed in an economically sustainable way by a dedicated team including the following disciplines: (a) Vascular Team, whose main focus is the diagnosis and treatment of impaired blood supply to the affected foot. This team usually includes vascular surgeons with long standing experience in peripheral ischemia treatment as well as interventional cardiologists or radiologists with extensive experience in peripheral endovascular revascularization procedures. (b) Foot Surgery Team, whose main focus is the surgical treatment of diabetic foot lesions, from drainage of acute suppurative infections to reconstruction of deformed Charcot Foot to major amputations.

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(c) Medical Team, whose main focus is to cope with the medical side of diabetic foot problems (e.g., antibiotic therapy, adequate glucose control, hypertension and hyperlipidemia management etc.) as well as to deal with the wide range of medical co-­ morbidities that will invariably be encountered when admitting to a hospital ward (e.g., acute renal failure, sepsis, heart failure, anticoagulation management, etc.). (d) Outpatient Team, whose main task is to manage patients before and after hospital admission. This includes outpatient management of DFU not requiring hospitalization by performing a thorough evaluation and diagnosis of the present condition and by applying the principles of adequate wound care, ensuring adequate offloading and follow-up when in remission. This team will often include podiatrists, wound care specialist nurses, orthotic technician as well as medical doctors with a diabetic foot care background.

ropathy, deformities and LOPS in the absence of infection or critical ischemia. (b) Ischemic Foot, that includes lesions whose main cause is an insufficient blood supply to the affected area, mostly due to occlusive PAD, in the absence of active infection. (c) Neuro-Ischemic Foot, which encompasses both the characteristics of the neuropathic foot and those of the ischemic foot, in the absence of active infection. (d) Infected Foot, a condition in which a DF lesion is associated with any degree of active infection and may or may not be associated with some degree of ischemia.

Such multidisciplinary teams should be connected with several other specialists that may be involved in diabetic foot care like the dialysis team, the emergency medicine team, the cardiology team, and the infectious disease specialists. Moreover, a complete multidisciplinary DF team should be nested in a hub-and-spoke model of clinical care, with the MDT being the hub and smaller peripheral centers the spokes with a fast-­ track connection to the hub center for more complex cases.

35.3 Neuropathic Foot

35.2 Diabetic Foot Pathogenetic Factors In order to clinically frame a newly discovered DF lesion, it is mandatory to appreciate its main pathogenetic factors: neuropathy, arterial disease, and infection. According to the main pathogenetic factor, it is possible to divide DF lesions into four main classes: (a) Neuropathic Foot, that includes DF patients with ulcers associated with peripheral neu-

The main task of the first clinician approaching a patient with an active DF lesion is to understand in which of these categories the patient lies, as the subsequent steps in management and the specialists involved in treatment will be very different according to the pathogenetic class.

Diabetic neuropathy typically affects peripheral nerve fibers in a symmetrical distal-proximal way resulting in a gradual loss of sensation (both touch and pain), in motor deficits and consequent abnormal postures. Neuropathic feet often develop deformities such as metatarsal head prominence with dislocation of plantar fat pads as well as claw toes, hallux valgus or tailor’s bunion. Such deformed feet, in turn, develop high pressure points mainly over the plantar surface as well as the dorsum of toes, thus inducing the overlying skin to thicken and become hyperkeratotic. This process, which in the short term represents a compensation mechanism of skin tissues coping with elevated contact pressures, in the long term evolves to a failure pathway as the hyperkeratotic skin becomes a callus behaving as a foreign body pressing over underlying soft tissues. Repetitive mechanical stress, in the absence of protective pain sensation, leads to hemorrhages under the callus and eventually ­development of a full thickness skin ulcer. Such ulcers can be defined “neuropathic” as their main

35  Infected Wound Bed Management: The Diabetic Foot

pathogenetic factor is represented by foot deformities as well as by abnormalities in proprioceptive and motor nerve fibers and by the loss of protective pain sensation (LoPS). A particularly extreme complication of peripheral diabetic neuropathy is Charcot Neuroarthropathy. In this condition, the severe damage to peripheral nerve fibers results in deep tissues aseptic inflammation leading to bone fractures and dislocations. Such feet, if not promptly immobilized in a total contact cast, will inevitably develop severe deformities and eventually ulceration. Unfortunately, in later stages, this complex situation often leads to major amputations. Clinically, neuropathic foot ulcers, developed in high pressure areas, are usually surrounded by hyperkeratotic margins and, if not infected, show a healthy, viable ulcer bed. Foot pulses are often present and, even in those cases with a quite heavy arterial arteriosclerotic burden, distal perfusion can be preserved. However, it is not uncommon to develop neuropathic ulcers in severe PAD. This condition will be addressed in the Neuro-Ischemic foot section. The mainstay of neuropathic foot ulcer treatment is offloading, thus removing the main trigger to the neuropathic foot ulcer pathway. The gold standard for offloading non-infected purely neuropathic (i.e. non-ischemic) foot ulcers is still considered Total Contact Casting (TCC). This technique consists of applying plaster of Paris or fiberglass bandages covering the whole foot, ankle and most of the leg up to just below the knee. The TCC achieves a reduction in plantar pressures by reducing stride length, foot speed, and by immobilizing the ankle during the propulsive phase of gait. The main drawbacks of the TCC are that they can be time consuming to apply, poorly accepted by patients, and can be associated with an increased risk of falls and/or cast induced ulcers particularly when applied by operators with less experience in this technique. For these reasons, removable ankle-foot-orthoses have been developed and their efficacy tested with randomized controlled trials versus TCC [18]. Most trials show that the healing rate in patients with foot


ulcers treated with TCC is overlapping with that of patients treated with a removable cast walker (RCW) even though the time-to-healing might be longer in the RCW treated group. The efficacy overlap is maximal when RCW are rendered irremovable by application of a security lace that discourages patients from removing the walker at home. At the same time, the RCW allows for emergency checks of foot skin in case of dressing staining or should the patient develop other signs of concern. The RCW achieves offloading by using custom made insoles applied in tall (i.e., knee high or mid-leg high) walkers with a rocker rigid sole, thus reducing both the peak plantar pressure and the time the ulcer bed is exposed to such pressure. Besides offloading, neuropathic foot ulcers’ treatment should be coupled to surgical debridement and appropriate wound care. Surgical debridement aims to remove all non-­ viable and possibly infected tissue as well as to activate the wound bed that in turn switches from chronic to acute. This means that wound bed cells are induced by the mechanical trigger to switch their secretory profile and their gene expression from a quiet inert one typical of chronic wounds to a more active one, typical of acute wounds, and aiming at tissue restoration. Moreover, appropriate wound care must be ensured in order to control edema, balance moisture, facilitate margin proliferation, and hamper bacterial or fungal growth. Nevertheless, when neuropathic foot ulcers do not resolve despite appropriate offloading, debridement, and wound dressings it is necessary to re-consider the original diagnosis (i.e., are there any even subtle signs of infection that have been originally overlooked? Is there any ischemia preventing tissues from receiving adequate blood supply to drive re-epithelization?). In those cases with a correct diagnosis and a neuropathic ulcer resistant to standard treatment, surgical offloading might be considered. Surgery in this case aims at removing bony prominences or correcting foot deformities responsible for high pressure points. Finally, it must be kept in mind that after a neuropathic foot ulcer undergoes re-­epithelization


there will still be a very high risk of re-ulceration. Therefore several guidelines [19] recommend that patients in secondary prevention use shoes with rocker or semi-rocker rigid soles and custom made total contact multilayer insoles. The customized insoles can achieve further offloading using inserts of softer material like latex in areas of known higher plantar pressure. The relationship between likelihood of developing a neuropathic foot ulcer and risk factors can be described by the following formula L  =  (P  ×  T)/S with L  =  lesion risk, P  =  Peak Pressure, T = time of pressure acting on foot tissues, and S  =  Surface of the area on which the weight force is acting. Therefore, the ideal preventive shoe will have a total contact shape to redistribute forces through a wider plantar surface, an offloading insole to reduce peak pressures on known high-risk areas, and a rocker sole to reduce the time that pressure acts on a specific foot area.

35.4 Ischemic Foot A diabetic foot can be defined “ischemic” when there is evidence of insufficient arterial blood supply to allow for ulcer healing. While uncommon causes of poor arterial blood supply to the foot do exist (like peripheral embolization, arterial dissection, arterial trauma, vasculitis, etc.) the large majority of diabetic foot ischemic lesions are caused by Peripheral Artery Disease (PAD). This condition consists of the progressive occlusion of lower limb arteries stemming from a chronic arteriosclerotic disease. Classically, PAD has been considered a mainly atherosclerotic disease. However, recent research has shown that while atheromas and typical atherosclerotic plaques represent the main pathologic feature of PAD affecting the suprainguinal and femoropopliteal region, calcific arteriosclerosis represents a prominent pathologic feature of infrapopliteal disease particularly in diabetic patients and is associated with higher amputation risk [20]. The clinical approach to follow when facing a suspected ischemic foot is well described in the recently developed Global Vascular Guidelines. This document focused on the management of

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critical limb-threatening ischemia (CLTI) in general but that adapts very well to the subpopulation of diabetic CLTI patients that, nowadays, represents the vast majority. The diagnostic pathway starts with a clinical exam performed because of a patient reported sign/symptom or as part of the periodic screening for diabetic foot complications that diabetic patients should undergo according to international consensuses[21, 22]., Patients with an ischemic foot may access medical care because of distal skin ulcers, mostly located at the toe-tip or on the heel area, or because of foot pain with ischemic clinical features (i.e., worse with limb elevation or with exercise, particularly at night, and improving with a dependent position). These conditions may be associated with skin gangrene, a condition of tissue necrosis associated with blackened discoloration of affected tissues and that may be dry (i.e., non-infected) or wet (i.e., infected). The clinical examination of the suspected ischemic foot aims at answering the following question:” Is the arterial blood flow to this foot enough to allow for ulcer healing and to avoid ischemic pain or does it need to be improved?” Answering this question is not always an easy task; however, in addition to pedal pulse palpation, in most cases, it can be done starting with a quantification of the degree of arterial disease with simple bedside tests. These include Ankle-­ Brachial-­Index (ABI) measurement and/or systolic Ankle Pressure (AP) measuring and/or Trans-cutaneous Oxygen partial pressure (TcPO2) and/or systolic Toe Pressure (TP). Cut-­ off values for any of these parameters are provided in the GVG guideline and allow for establishing the degree of ischemia a patient is affected by. It has to be kept in mind, however, that medial arterial calcifications (MAC) are very frequent in patients with long standing diabetes as well as renal failure. MAC may falsify ABI, AP, and TP measurements as a higher pressure needs to be generated to compress the rigid ­arterial vessel, thus providing a falsely elevated pressure reading. On the other hand, an ABI, AP, or TP in the CLTI range is to be considered valid until proven otherwise as calcification will only give falsely high readings. Caution must be


35  Infected Wound Bed Management: The Diabetic Foot

advised when interpreting ostensibly normal pressure readings, however, since MAC in the ischemic limb can actually elevate arterial pressures to what would ostensibly be considered normal levels. Hence, it is always recommended to obtain several different measures of arterial perfusion to corroborate the validity of ankle or toe pressures. The clinical evaluation is usually completed by an imaging test, particularly if a revascularization strategy is considered. This is usually represented initially by a color-Doppler ultrasound imaging as it allows for safe, inexpensive and quick anatomic and velocimetric evaluation of the whole lower limb arterial tree. If further imaging is needed, MRA or CTA may be considered. However, if an endovascular revascularization will be attempted, imaging might be completed with the diagnostic angiography that precedes the angioplasty attempt. If the complete clinical evaluation shows that the arterial blood flow to the affected foot is insufficient, a diagnosis of Critical Limb Threatening Ischemia (CLTI) is done and the next step in management consists in deciding if a revascularization procedure is to be attempted and with which strategy. The GVG guideline suggest a clinical approach based on the acronym PLAn that stands for P = Patient risk estimation, L = Limb staging, and An = Anatomic pattern of disease.

are achieving ulcer healing, pain control, and functional limb salvage. However, revascularization procedures are associated with periprocedural risks that must be balanced with the likelihood of achieving the revascularization goals. If periprocedural risks turn out to outweigh the potential benefits, patients may be better served with palliative medical care or with a primary major amputation. A model for estimating procedural risks and expected life-expectancy has been proposed by the Vascular Quality Initiative (VQI) that evaluated a cohort of more than 38,000 patients undergoing infra-inguinal revascularization procedures [23]. There are also available free online calculators that allow clinicians to quickly estimate these risks [24].

35.4.1 Patient Risk Estimation

The definition of the anatomic pattern of disease is to be done based upon angiographic data, best supported by pre-angiographic imaging with colorDoppler ultrasound scanning as well as any other imaging technique used in the pre-op evaluation.

Patients with a diabetic ischemic foot are usually frail, with advanced age and affected by multiple comorbidities. The main goals of CLTI treatment

35.4.2 Limb Staging Limb evaluation aiming to define the disease severity is crucial in deciding whether a revascularization procedure could be beneficial or not. The GVG suggests the use of WIfI classification (Table 35.2) derived matrixes to relate the ischemia degree with infection severity and wound extension. Generally speaking, the worse the ischemia grade and the WIfI stage the greater are the benefits of a revascularization attempt.

35.4.3 Anatomic Pattern of Disease

Table 35.2  Staging and Grading of limb ischemia according to the Global Vascular Guidelines and corresponding expected clinical benefit from a limb revascularization [11] WIfI Ischemia Grade

3 2 1 0

N/A N/A Very Low benefit Very Low benefit 1 WIfI stage

High benefit Low benefit Low benefit

High benefit Moderate benefit Moderate benefit

High benefit High benefit Moderate benefit

Very Low benefit 2

Very Low benefit

Very Low benefit



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The GVG suggests defining the anatomic pattern and the possible revascularization strategy using a standardized staging system like the Global Limb Anatomic Staging System whose main advantage is to define a Target Arterial Path, i.e., the optimal anatomic route that might be followed to restore blood supply to the foot, thus allowing evaluation of its feasibility. The above clinical pathway is suggested by the GVG for evaluation and treatment of any patient with a foot lesion associated with CLTI. However, it has to be kept in mind that any time a diabetic patient is to undergo any kind of foot surgery, it is good clinical practice to ensure adequate vascularity to the foot. In cases of arterial insufficiency, preliminary restoration of pedal blood flow can better ensure healing of the operative site.

35.5 Neuro-Ischemic Foot A neuro-ischemic foot is the result of a combination of neuropathic and ischemic features. They represent roughly 25–30% [25] of all diabetic foot lesions and are characterized by a very variable clinical appearance with attributes of both neuropathic as well as ischemic appearing lesions. It is crucial to correctly detect neuro-ischemic feet as they will not heal if only one of the two concomitant pathogenetic factors is addressed. Therefore, a patient with a neuro-ischemic foot ulcer that correctly utilizes the appropriate cast walker device will not see a relevant clinical improvement unless revascularization of the limb occurs as well. At the same time, neuro-ischemic patients with digital or calcaneal necrosis that receive adequate restoration of blood flow to the affected foot area will not heal unless adequate offloading is ensured. In consideration of all this, the IWGDF guidelines recommend thorough vascular evaluation also in DFU with a typical neuropathic appearance as well as ensuring adequate offloading also in lesions with a typical ischemic appearance.

35.6 Infected Foot Diabetic Foot Infections (DFI) result from the invasion and proliferation of bacteria or fungi within foot tissues causing an inflammatory response by the host as well as tissues breakdown. Clinically, DFI manifests with the typical signs and symptoms of inflammation whose detection is used as the main diagnostic criteria. As the vast majority of DFI develop in skin ulcers or open wounds, they are to be considered colonized by bacteria until proven otherwise. The diagnosis of DFI therefore cannot be done on isolated culture data, as cultures will be positive in most cases of simple wound colonization. Hence, the diagnosis of infection is based primarily on clinical signs and symptoms [26]. Moreover, it has to be kept in mind that peripheral neuropathy as well as PAD may increase the risk of developing DFI while, at the same time, mask the appearance of clinical signs of inflammation. For example, an infected ischemic foot will hardly appear hot or hyperaemic as the arterial blood impairment will not allow an increase in blood flow to the affected area. As a multi-national panel of experts in the field of DF care, the International Working Group on the Diabetic Foot (IWGDF) has developed solid guidelines on the management DFI based on a systematic review of the available literature [27]. The diagnostic criteria recommended by the IWGDF (Table 35.3) for DFI have been validated by at least 2 large prospective cohort studies and have subsequently been included in the Society for Vascular Surgery WIfI classification for the foot infection (fI) component. While approaching a DF lesion for the first time, it is essential to evaluate the infective status according to the aforementioned diagnostic criteria as well as the vascular status and the presence/ absence of neuropathy or deformities. Patients with severe infections must be hospitalized as soon as possible for emergent surgical drainage. While some national guidelines, as the English NICE Guidance [28], report a 24-h time limit within which a patient with a DFI should be referred to the multidisciplinary foot care team,

35  Infected Wound Bed Management: The Diabetic Foot Table 35.3  Classification of foot infections according to the International Working Group on Diabetic Foot [27] Clinical definition/classification of infection Uninfected No systemic or local signs of infection Infected Presence of at least 2 of the following criteria: – Local swelling or induration – Erythema >0.5 cma around the wound – Local tenderness or pain – Local increased warmth – Purulent discharge No other possible explanations are present for the detected inflammatory changes (e.g., trauma, gout, acute Charcot neuro-osteoarthropathy, fracture, thrombosis or venous stasis) Absence of systemic manifestations (see below) but presence of both the following criteria: – Involvement of only skin or subcutaneous tissue (not any deeper tissues), – Erythema does not extend >2 cma around the wound Absence of systemic manifestations (see below) but presence of at least one of the following criteria: – Erythema extending>2 cma from the wound margin, – Tissue deeper than skin and subcutaneous tissues (e.g., tendon, muscle, joint, bone) Any DFI associated to manifestations of systemic inflammatory response syndrome (SIRS), and thus with at least 2 of the following criteria: – Temperature > 38 °C o  90 bpm – Respiratory rate > 20/min or PaCO2 12.000/mm3 o 10% Infection involving boneb

IWGDF grade 1 (uninfected)

2 (mild infection)


several other reports have shown that purulent collections, particularly when associated with rapid systemic deterioration or signs of elevated compartmental pressure, necessitate an urgent drainage, typically within a few hours from first access to medical care [7, 8, 29, 30]. This “as-­ soon-­ as-possible” approach, based on a rapid multidisciplinary diabetic foot team referral, has been demonstrated to perform particularly well also for DFI of moderate and mild severity both in terms of final outcomes [31] and in terms of costs [32] . The expression “time is tissue” has been proposed to emphasize the importance of time management in determining the final fate of the limb [33].

35.7 Diabetic Foot Life- or LimbThreatening Infections Several pathologic entities may be responsible of an infective life or limb threatening condition. We report herein the most common causes of moderate to severe DFI.

3 (moderate infection or limb threatening)

4 (severe infection or life threatening)

35.7.1 Deep Suppurative Infections This category includes mainly foot abscesses (Fig.  35.1) and phlegmons (Fig.  35.2). The former are defined as purulent collections localized within a cavity that has formed de-novo from destruction or mechanical dissection of surround-

Add “O” after grade 3 or 4

Inflammatory changes can be present in any foot area, not necessarily contiguous to the skin ulcer b If osteomyelitis is demonstrated in the absence of≥2 signs/symptoms of local or systemic inflammation, classify as either grade 3(O) (if 90%

Suggested Management Treat for DFO

Likely osteomyelitis (i.e., “more yes than no”)


Consider starting treatment but further tests might be needed

Possible osteomyelitis


Treatment may be started but further tests are usually necessary

Unlikely osteomyelitis

 70 mm/h with no other plausible causes – Ulcer not improving despite adequate offloading and vascular supply – Ulcer associated to infection for more than 2 weeks No sign or symptom of infection Negative imaging Superficial ulcer from less than 2 weeks

Modified from Berendt AR, et al. Diabetic foot osteomyelitis: a progress report on diagnosis and a systematic review of treatment. Diabetes Metab Res Rev. 2008;24:S145-S61


35  Infected Wound Bed Management: The Diabetic Foot Table 35.5  Factors to consider and potential empiric antibiotic regimens for diabetic foot infections Infection severity IWGDF grade 2

IWGDF grade 3 or 4

Additional factors No complicating features ß-lactam allergy or intolerance Recent antibiotic exposure High risk for MRSA No complicating features Recent antibiotics

Usual pathogen(s) GPC

Potential empirical regimens S-S pen; first gen ceph


Clindamycin; FQ; T/S; macrolide; doxy


ß-l-ase-1; T/S; FQ


Linezolid; T/S; doxy; macrolide


ß-l-ase 1; second/third gen ceph


Macerated ulcer or warm climate Ischaemic limb/ necrosis/gas forming MRSA risk factors

GNR, including pseudomonas GPC ± GNR ± anaerobes

ß-l-ase 2; third gen ceph; group 1 carbapenem (depends on prior therapy; seek advice) ß-l-ase 2; S-S pen + ceftazidime; S-S pen + cipro; group 2 carbapenem ß-l-ase 1 or 2; group 1 or 2 carbapenem; second/ third gen ceph + clindamycin or metronidazole

Risk factors for resistant GNR



Consider adding, or substituting with, glycopeptides; linezolid; daptomycin; fusidic acid T/S (±rif)b; doxycycline Carbapenems; FQ; aminoglycoside and colistin

ß-l-ase, ß-lactam ß-lactamase inhibitor, ß-l-ase 1 amoxicillin/clavulanate, ampicillin/sulbactam, ß-l-ase 2, ticarcillin/ clavulanate, piperacillin/tazobactam, doxy doxycycline, ESBL extended-spectrum ß-lactamase-producing organism, FQ fluoroquinolone with good activity against aerobic Gram-positive cocci (e.g., levofloxacin or moxifloxacin), gen generation, GNR Gram-negative rod, GPC Gram-positive cocci (staphylococci and streptococci), Group 1 carbapenem ertapenem, Group 2 carbapenem imipenem, meropenem, doripenem, ceph cephalosporin, MRSA methicillin-resistant Staphylococcus aureus, Pip/tazo piperacillin/tazobactam, S-S pen semisynthetic penicillinase-resistant penicillin, cipro antipseudomonal fluoroquinolone, e.g., ciprofloxacin, T/S trimethoprim/sulfamethoxazole, rif rifamp(ic)in Modified from Lipsky BA, et al.; International Working Group on the Diabetic Foot (IWGDF). Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update). Diabetes Metab Res Rev. 2020 Mar;36 Suppl 1:e3280. doi: 10.1002/dmrr.3280. PMID: 32176444

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5. Lavery LA, Armstrong DG, Wunderlich RP, Tredwell J, Boulton AJ.  Diabetic foot syndrome: evaluating the prevalence and incidence of foot pathology in Mexican Americans and non-Hispanic whites from a diabetes disease management cohort. Diabetes Care. 2003;26:1435–8. 6. Iversen MM, Tell GS, Riise T, et al. History of foot ulcer increases mortality among individuals with diabetes: ten-year follow-up of the Nord-Trøndelag health study, Norway. Diabetes Care. 2009;32:2193–9. 7. Faglia E, Clerici G, Caminiti M, Quarantiello A, Gino M, Morabito A.  The role of early surgical debridement and revascularization in patients with diabetes and deep foot space abscess: retrospective review of 106 patients with diabetes. J Foot Ankle Surg. 2006;45:220–6. 8. Nickinson ATO, Bridgwood B, Houghton JSM, Nduwayo S, Pepper C, Payne T, Bown MJ, Davies RSM, Sayers RD. A systematic review investigating the identification, causes, and outcomes of delays

402 in the management of chronic limb-threatening ischemia and diabetic foot ulceration. J Vasc Surg. 2020;71(2):669–681.e2. 9. Monteiro-Soares M, Russell D, Boyko EJ, Jeffcoate W, Mills JL, Morbach S, Game F. International working group on the diabetic foot (IWGDF). Guidelines on the classification of diabetic foot ulcers (IWGDF 2019). Diabetes Metab Res Rev. 2020;36(Suppl 1):e3273. 10. Mills JL Sr, Conte MS, Armstrong DG, Pomposelli FB, Schanzer A, Sidawy AN, Andros G.  Society for Vascular Surgery Lower Extremity Guidelines Committee. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg. 2014;59(1):220–34. e1–2. Epub 2013 Oct 12. 11. Conte MS, Bradbury AW, Kolh P, et  al. Global vascular guidelines on the management of chronic limb-­ threatening ischemia. Eur J Vasc Endovasc Surg. 2019;58(1S):S1–S109.e33. ejvs.2019.05.006. Epub 2019 Jun 8. Erratum in: Eur J Vasc Endovasc Surg. 2020 Mar;59(3):492– 493. Erratum in: Eur J Vasc Endovasc Surg. 2020 Jul;60(1):158–159. PMID: 31182334; PMCID: PMC8369495. 12. Calhoun JH, Cantrell J, Cobos J, Lacy J, Valdez RR, Hokanson J, Mader JT.  Treatment of diabetic foot infections: Wagner classification, therapy, and outcome. Foot Ankle. 1988;9:101–6. 13. Lavery LA, Armstrong DG, Harkless LB.  Classification of diabetic foot wounds. J Foot Ankle Surg. 1996;35(6):528–31. https://doi. org/10.1016/s1067-­2516(96)80125-­6. 14. Ince P, Abbas ZG, Lutale JK, Basit A, Ali SM, Chohan F, et  al. Use of the SINBAD classification system and score in comparing outcome of foot ulcer management on three continents. Diabetes Care. 2008;31(5):964–7. 15. Rogers LC, Andros G, Caporusso J, Harkless LB, Mills JL Sr, Armstrong DG.  Toe and flow: essential components and structure of the amputation prevention team. J Vasc Surg. 2010;52(3 Suppl):23S–7S. 16. Patel N, Tan TW, Weinkauf C, Rice AH, Rottman AM, Pappalardo J, Goshima K, Zhou W. Economic value of podiatry service in limb salvage alliance. J Vasc Surg. 2022;75(1):296–300. jvs.2021.07.126. Epub 2021 Jul 24. PMID: 34314830; PMCID: PMC8900989. 17. Ferraresi R, Casini A, Caminiti M, Losurdo F, Clerici G.  Multidisciplinary approach to diabetic foot: a challenge of expertises. G Ital Cardiol (Rome). 2018;19(9):495–503. https://doi. org/10.1714/2951.29668. 18. Elraiyah T, Prutsky G, Domecq JP, Tsapas A, Nabhan M, Frykberg RG, Firwana B, Hasan R, Prokop LJ, Murad MH.  A systematic review and meta-analysis of off-loading methods for diabetic foot ulcers. J Vasc

G. Clerici et al. Surg. 2016;63(2 Suppl):59S–68S.e1–2. https://doi. org/10.1016/j.jvs.2015.10.006. 19. Bus SA, Armstrong DG, van Deursen RW, Lewis JE, Caravaggi CF, Cavanagh PR, International Working Group on the Diabetic Foot. IWGDF guidance on footwear and offloading interventions to prevent and heal foot ulcers in patients with diabetes. Diabetes Metab Res Rev. 2016;32(Suppl 1):25–36. https://doi. org/10.1002/dmrr.2697. 20. Losurdo F, Ferraresi R, Ucci A, Zanetti A, Clerici G, Zambon A. Association of infrapopliteal medial arterial calcification with lower-limb amputations in high-­ risk patients: a systematic review and meta-analysis. Vasc Med. 2021;26(2):164–73. 7/1358863X20979738. 21. American Diabetes Association Professional Practice Committee, Draznin B, Aroda VR, Bakris G, Benson G, Brown FM, Freeman R, Green J, Huang E, Isaacs D, Kahan S, Leon J, Lyons SK, Peters AL, Prahalad P, JEB R, Young-Hyman D. 12. Retinopathy, neuropathy, and foot care: standards of medical care in diabetes-­2022. Diabetes Care. 2022;45(Suppl 1):S185–94.­S012. 22. National Evidence-Based Guideline on Prevention, Identification and Management of Foot Complications in Diabetes (Part of the Guidelines on Management of Type 2 Diabetes). 2011. Melbourne Australia. 23. Simons JP, Schanzer A, Flahive JM, Osborne NH, Mills JL Sr, Bradbury AW, Conte MS. Survival prediction in patients with chronic limb-threatening ischemia who undergo infrainguinal revascularization. Eur J Vasc Endovasc Surg. 2019;58(1S):S120–S134. e3. Epub 2019 May 28. 24.­ infrainguinal-­revascularization-­open-­or-­pvi-­for-­clti-­ 30-­day-­and-­2-­year-­survival. 25. Prompers L, Huijberts M, Apelqvist J, Jude E, Piaggesi A, Bakker K, Edmonds M, Holstein P, Jirkovska A, Mauricio D, Ragnarson Tennvall G, Reike H, Spraul M, Uccioli L, Urbancic V, Van Acker K, van Baal J, van Merode F, Schaper N. High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study. Diabetologia. 2007;50(1):18–25.­006-­0491-­1. Epub 2006 Nov 9. 26. Lipsky BA, Senneville É, Abbas ZG, Aragón-Sánchez J, Diggle M, Embil JM, Kono S, Lavery LA, Malone M, van Asten SA, Urbančič-Rovan V, Peters EJG, International Working Group on the Diabetic Foot (IWGDF). Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update). Diabetes Metab Res Rev. 2020;36(Suppl 1):e3280. dmrr.3280. 27. Senneville É, Lipsky BA, Abbas ZG, Aragón-­ Sánchez J, Diggle M, Embil JM, Kono S, Lavery LA, Malone M, van Asten SA, Urbančič-Rovan V, Peters EJG. Diagnosis of infection in the foot in dia-

35  Infected Wound Bed Management: The Diabetic Foot betes: a systematic review. Diabetes Metab Res Rev. 2020;36(Suppl 1):e3281. dmrr.3281. 28. National Institute for Health and Clinical Excellence (NICE). Diabetic Foot Problems. Inpatient management of diabetic foot problems. London: National Institute for Health and Clinical Excellence (NICE); 2011. 29. Uçkay I, Aragón-Sánchez J, Lew D, Lipsky BA.  Diabetic foot infections: what have we learned in the last 30 years? Int J Infect Dis. 2015;40:81–91. 30. Edmonds M.  Body of knowledge around the diabetic foot and limb salvage. J Cardiovasc Surg. 2012;53(5):605–16. 31. Smith-Strøm H, Iversen MM, Igland J, Østbye T, Graue M, Skeie S, Wu B, Rokne B. Severity and duration of diabetic foot ulcer (DFU) before seeking care as predictors of healing time: a retrospective cohort study. PLoS One. 2017;12(5):e0177176. https:// PMID: 28498862; PMCID: PMC5428931. 32. Joret MO, Osman K, Dean A, Cao C, van der Werf B, Bhamidipaty V. Multidisciplinary clinics reduce treatment costs and improve patient outcomes in diabetic foot disease. J Vasc Surg. 2019;70(3):806–14. https:// Epub 2019 Mar 6. 33. Setacci C.  Time is tissue. J Endovasc Ther. 2012;19(4):515–6. https://doi. org/10.1583/12-­3933E.1. 34. Ledermann HP, Morrison WB, Schweitzer ME, Raikin SM. Tendon involvement in pedal infection: MR analysis of frequency, distribution, and spread of infection. AJR Am J Roentgenol. 2002;179(4):939–47. 35. Mismar A, Yousef M, Badran D, Younes N. Ascending infection of foot tendons in diabetic patients. Int J Low Extrem Wounds. 2013;12(4):271–5. https://doi. org/10.1177/1534734613493290. Epub 2013 Sep 16. 36. Khanna AK, Tiwary SK, Kumar P, Khanna R, Khanna A.  A case series describing 118 patients with lower limb necrotizing fasciitis. Int J Low Extrem Wounds. 2009;8(2):112–6. https://doi. org/10.1177/1534734609334809. 37. Tarricone A, Mata K, Gee A, Axman W, Buricea C, Mandato MG, Trepal M, Krishnan P.  A systematic review and meta-analysis of the effectiveness of LRINEC score for predicting upper and lower extremity necrotizing fasciitis. J Foot Ankle Surg. 2022;61(2):384–9. jfas.2021.09.015. Epub 2021 Sep 20. 38. Schmitt SK. Osteomyelitis. Infect Dis Clin N Am. 2017;31(2):325–38. idc.2017.01.010. 39. Garwood CS, Kim PJ. Relevance of osteomyelitis to clinical practice. In: Boffelli TJ, editor. Osteomyelitis


of the foot and ankle. 1st ed. Switzerland: Springer; 2015. p. 1–11. 40. Chihara S, Segreti J.  Osteomyelitis. Dis Mon. 2010;56(1):5–31. disamonth.2009.07.001. 41. Hawkins BK, Barnard M, Barber KE, Stover KR, Cretella DA, Wingler MJB, Wagner JL.  Diabetic foot infections: a microbiologic review. Foot (Edinb). 2022;51:101877. foot.2021.101877. Epub 2021 Oct 25. 42. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. 3. Osteomyelitis associated with vascular insufficiency. N Engl J Med. 1970;282(6):316–22. NEJM197002052820606. 43. Cierny G 3rd, Mader JT, Penninck JJ. A clinical staging system for adult osteomyelitis. Clin Orthop Relat Res. 2003;414:7–24. blo.0000088564.81746.62. 44. Buckholz JM. The surgical management of osteomyelitis: with special reference to a surgical classification. J Foot Surg. 1987;26(1 Suppl):S17–24. 45. Keel SB.  Pathologic diagnosis of osteomyelitis. In: Boffelli TJ, editor. Osteomyelitis of the foot and ankle. 1st ed. Switzerland: Springer; 2015. p. 49–53. 46. Cecilia-Matilla A, Lázaro-Martínez JL, Aragón-­ Sánchez J, García-Morales E, García-Álvarez Y, Beneit-Montesinos JV.  Histopathologic characteristics of bone infection complicating foot ulcers in diabetic patients. J Am Podiatr Med Assoc. 2013;103(1):24–31. 47. Newman LG, Waller J, Palestro CJ, Schwartz M, Klein MJ, Hermann G, Harrington E, Harrington M, Roman SH, Stagnaro-Green A.  Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by leukocyte scanning with indium in 111 oxyquinoline. JAMA. 1991;266(9):1246–51. https:// 48. Kosmopoulou OA, Dumont IJ. Feasibility of percutaneous bone biopsy as part of the management of diabetic foot osteomyelitis in a 100% neuropathic, grade 3 IDSA/IWGDF population on an outpatient basis. Int J Low Extrem Wounds. 2020;19(4):382–7. https://doi. org/10.1177/1534734620902609. Epub 2020 Jan 30. 49. Féron F, de Ponfilly GP, Potier L, Gauthier DC, Salle L, Laloi-Michelin M, Munier AL, Jacquier H, Vidal-­ Trécan T, Julla JB, Carlier A, Abouleka Y, Venteclef N, Grall N, Mercier F, Riveline JP, Senneville É, Gautier JF, Roussel R, Kevorkian JP.  Reliability and safety of bedside blind bone biopsy performed by a Diabetologist for the diagnosis and treatment of diabetic foot osteomyelitis. Diabetes Care. 2021;44(11):2480–6.­ 3170. Epub 2021 Sep 2.


Osteomyelitis Giovanni Vicenti, Guglielmo Ottaviani, and Biagio Moretti

36.1 Introduction Osteomyelitis is characterized as bone inflammation brought on by an infectious agent [1]. Understanding the etiology of the disease, the common and uncommon etiological agents, the principles of anti-infective therapy, and when and how to perform surgical debridement and reconstructive techniques are all necessary for the successful management of osteomyelitis. It is difficult to determine the pathophysiology, imaging, and classification of osteomyelitis because it depends on the patient’s age (child vs. adult), the duration and intensity of the infection (acute vs. chronic), the route of spread (hematogenous vs. contiguous focus), the patient’s immune and vascular status, as well as the affected area.

36.2 Classification Osteomyelitis has historically been categorized using the Waldvogel classification, which was introduced in 1970 [2]. The source of the infec-

G. Vicenti · G. Ottaviani (*) · B. Moretti U.O.C Ortopedia e traumatologia, Policlinico di Bari, Università degli studi di Bari “Aldo Moro”, Bari, Italy e-mail: [email protected]

tion (hematogenous or contiguous), the existence of generalized vascular disease, and the length of the infection were all included in this descriptive classification system (acute, sub-acute, and chronic). The 1977 publication of Ger’s classification recognized the role of the soft tissue situation in the surgical decision-making process. This classification categorizes soft tissue conditions as simple sinus, chronic superficial ulcer, multiple sinuses, multiple skin-lined sinuses, or multiple sinuses. Through the publication of a classification system that emphasized a more comprehensive approach to the patient and acknowledged the significance of immune competency and the physiological ability of the host to effect healing, Cierny and Mader revolutionized our understanding of osteomyelitis in 1984 [3]. This system included categorization based on the disease’s anatomical characteristics and the physiological state of the host (Fig. 36.1). The Cierny and Mader classification however failed to provide specific, objective criteria according to which the C-host, whom they deemed unsuitable for surgery, should be defined. McPherson et al. attempted to address the shortcomings of the Cierny and Mader host classification system by modifying it to include specific objective criteria [4]. But several and more articulated classifications have been developed.

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,


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406 Fig. 36.1 Cierny– Mader Classification: (a) medullary osteomyelitis (early hematogenous); (b) superficial osteomyelitis (early contiguous); (c) localized osteomyelitis; and (d) diffuse osteomyelitis





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36.3 Pathogenesis Invasion of the bone by pathogens leads to an acute reaction by the body and inflammatory factors. Microscopic examination of the bone demonstrates the presence of areas of suppurative inflammation in which bacteria and inflammatory cells are deposited. The inflammation causes progressive destruction of the bone matrix and subsequent occlusion of blood vessels. As a result, areas of ischemia are created that contribute to tissue necrosis. Ischemia also makes it impossible for other inflammatory cells and antibiotics to reach the site of infection. A hypervascularized rim forms around these areas, which increases the activity of osteoclasts and osteoblasts resulting in  localized osteoporosis and apposition of new exuberant osseous tissue [5].

36.4 Anatomo-Pathological Lesions Four anatomopathological lesions typical of osteomyelitis are recognized in this process and deserve to be described (Fig. 36.2). Brodie’s abscess represents a purulent intraosseous collection, often surrounded by a hypervascular orb [6]. It is considered a typical lesion of acute osteomyelitis even though it manifests over a period ranging from 1 week to 1 year and often



the typical symptoms are not associated. By MRI, a fluid lesion, frequently metaphyseal, surrounded by a vascularized orb can be visualized. Sequestrum, on the other hand, represents the typical lesion of chronic osteomyelitis [1]. It is an area of devascularized bone surrounded by an area of necrosis. As explained earlier this makes treatment with antibiotics ineffective, as they cannot reach the site of infection. It can be found on plain radiographs and, even better, on CT. Involucrum is the sclerotic area surrounding the sequestrum [7]. Cloaca, on the other hand, is the break in the sequestrum that allows communication with the periosteum and in some cases with the outside, taking the name fistula.

36.5 Pathogens Osteomyelitis are frequently polymicrobial infections, especially when caused by contiguity with an ulcer. Hematogenous osteomyelitis, on the other hand, is usually caused by a single pathogenic organism. The most frequently isolated pathogen is Staphylococcus aureus. This is probably due to its numerous virulence factors. Adhesins allow colonization of implanted tissues and materials. The pathogen has the ability to evade host defenses and invade cells. It can also remain viable within host cells, which


Fig. 36.2  Anatomopathological lesions: (a) acute hematogenous osteomielitys (1. nidus); (b) subacute osteomielytis (2. Brodie’s abscess); and (c) chronic osteomyelitis (3. sinus; 4. sequestrum; 5. fistula)

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would explain the high rate of recurrence of infections [8]. Staphylococcus aureus, along with other bacterial species, is capable of producing biofilm, a highly structured community of sessile bacteria surrounded by a polymeric extracellular matrix. This structure, which is difficult for antibiotics to penetrate, surrounds colonies of bacteria that are metabolically inactive and therefore less sensitive to their effect [9]. Although some antibiotics have a greater effect against biofilm, the best therapy is surgical debridement.

36.6 Diagnosis The diagnosis of osteomyelitis is using a multidisciplinary approach involving laboratory medicine, imaging, and pathology. Symptomatology is highly variable and nonspecific. Acute osteomyelitis may be characterized by more obvious symptoms such as fever, pain, and swelling. Chronic forms, on the other hand, have more subtle symptomatology; fever may not be present, bone pain, local swelling, and, in some cases, fistulae are manifest. Confirmation of osteomyelitis requires several diagnostic procedures as described below.

36.6.1 Microbiology and Histopathology In any type of osteomyelitis, the identification of the pathogen is crucial. This can be done by several tools. Blood cultures are diagnostic only in hematogenous osteomyelitis. The use of local swabs is now considered obsolete, collecting samples from the surface of an ulcer or even from the depth of the ulcer often results in contamination by nonpathogenic microorganisms that have colonized the site. The suggestion is to take five biopsy samples of the deep perilesional tissue, around the implant or debridement site [10]. All samples should be analyzed for Gram + and Gram −.

36.6.2 Laboratory Studies The use of laboratory tests can be helpful in the diagnosis and follow-up of osteomyelitis. Erythrocyte sedimentation rate (ESR) is frequently high but its changes are too slow to allow adequate follow-up. In contrast, the concentration of C-reactive protein (CRP) is highly sensitive and its kinetics allow the evaluation of the effectiveness of therapy. In fact, it increases as early as the first hours following the acute phase and decreases in about a week after the start of effective treatment. The use of these parameters in combination makes it possible to exponentially increase the sensitivity and specificity of the tests, moreover with the addition of local sampling the sensitivity reaches 100% [11]. The white blood cell count (WBC) may also be normal in chronic osteomyelitis [12]. However, all of these values, despite being particularly sensitive, are highly nonspecific and, by themselves, do not allow for a definite diagnosis.

36.6.3 Imaging Procedures All imaging procedures can be used to complete the diagnosis of osteomyelitis. Plain radiography is the basis of diagnosis and follow-up (Fig.  36.3). It allows visualization of local swelling that occurs as early as 2–3  days; after about 10–12  days, on the other hand, the presence of a bone defect can be assessed. Sonography is a useful tool for the evaluation of osteomyelitis in the acute phase. It allows excellent visualization of soft tissues, and because of its low invasiveness it can be used for the diagnosis of pediatric osteomyelitis [13]. CT allows detailed visualization of bone structures and surrounding soft tissues, consequently it is a valuable tool for the study of chronic osteomyelitis. However, it often suffers from artifacts caused by the simultaneous presence of metal implants [14] (Fig. 36.4).MRI, on the other hand, is ideal for the study of the early stages of the disease and allows an even more accurate study of the soft tissues. The presence of bone edema is a typical sign of osteomyelitis, but

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Fig. 36.3  Plain radiography of chronic osteomyelitis showing diffuse osteolysis, periosteal reaction, and soft tissues involvement

Fig. 36.4  CT-scan of chronic osteomyelitis showing diffuse osteolysis, osteoporosis, sequestrum, and air bubbles inside soft tissue

on the other hand, it does not allow for adequate follow-up as it may persist for months after the resolution of the disease [15]. Bone scintigraphy can be used with different types of radiopharma-

ceuticals. Leukocytes labeled with indium-111 or technetium-99 m can be used for early diagnosis of acute osteomyelitis with high specificity and high sensitivity.

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Positron emission tomography (PET) labeled with fluorine-18-fluoro-D-deoxyglucose (FDG) is a highly sensitive and specific test that combined with CT allows accurate visualization of lesions [16].

36.7 Treatment The goal of treatment is always the definitive eradication of the pathogen, however the options available are different if the osteomyelitis is acute or chronic.

36.7.1 Acute Osteomyelitis The first line of treatment for acute osteomyelitis (Fig.  36.5) is always antibiotic therapy [17]. As mentioned earlier, successful therapy depends on correct diagnosis and, most importantly, isolation of the pathogen. To avoid the emergence of resistance, a consultation with an infectiologist is always recommended and usually the combination of two antibiotics is chosen. The parameters to be evaluated in the choice of antibiotics are bone-wide distribution, adverse effects, cost, and duration. a


36.7.2 Chronic Osteomyelitis Regarding chronic osteomyelitis, it is now known that antibiotic therapy alone cannot completely eradicate the infection. Surgery has therefore become the cornerstone of treatment. Fundamental turns out to be the study of the patient and classification of the disease. The classification most commonly used nowadays is the Cierny–Mader classification, which in addition to local conditions, allows us to divide the host into three classes: host-A healthy patients with low perioperative risk; host-B patients with local or systemic immunologic changes; and host-C patients in whom treatment may be more dangerous than the disease. After accurately studying the location of the disease and the patient’s comorbidities, one should try to correct the immunological status of the patient: nutritional status should be optimized, and metabolic alterations and anemia should be corrected. To allow proper wound healing after surgical resection, one must ascertain the patient’s vascular status (by pulsoximetry, Doppler, or CT angiography) and correct it when possible.Salvage surgery involves an extensive debridement of bone and soft tissue, and resection surgery tries to maintain c

Fig. 36.5  Clinical progression of acute osteomyelitis: (a) 1 day; (b) 3 days; and (c) 4 days

36 Osteomyelitis

bone stability. Resection of the osteomyelitis focus should be radical and include healthy margins (“tumor-like resection”), it is always better to remove a few more segments than less [18]. However, the extent of resection may cause instability of the treated skeletal segment, leading to an advancement in the Cierny–Mader classification from stage III to IV, in which case additional therapies are necessary. The various options allow the bone defect to be filled acutely or by multi-step treatments. In acute, it is possible to fill the defect by the placement of an autologous graft, this can be taken from numerous anatomical sites and may or may not be associated with vascularized pedicles and soft tissue flaps. If, however, a high risk of acute recurrence remains, it is possible to reclaim the osteomyelitis focus by placing a cement spacer to fill the defect, as described by Masquelet [19]. The technique describes the use of a simple poly-methyl-­ methacrylate (PMMA) spacer; however, it can be fortified with antibiotics to increase its eradicating power and decrease the rate of recurrence. Retention of the PMMA spacer within the defect for at least 4–6  weeks causes a “foreign body reaction” that leads to the formation of a highly vascularized “pseudomembrane.” The second step involves the incision of the “pseudomembrane,” the removal of the PMMA spacer, and placement of bone grafts in what is called a “biological chamber.” A 2016 meta-analysis by an Italian group of 17 papers (between 2000 and 2016) analyzed variables from 427 patients. An 89.7% union rate was reported with 91.1% eradication of infection in bone defects between 0.6 and 26 cm [20]. Another technique, described by Ilizarov [21] in the 1970s, allows for the simultaneous treatment of bone and soft tissue defects and is called distractional osteogenesis. Through the use of a circular external fixation system, devised by the author himself, it is possible to resect large bone segments while still maintaining limb stability and still allowing load bearing.


Then an osteotomy is made at the metaphyseal site, and again thanks to Ilizarov’s “apparatus,” it is possible to fill the defect by progressive distraction of the bony callus, creating a “regenerate” following the principles of distraction osteogenesis. The most recent meta-analyses report a cure rate of 97.26%, with unsatisfactory results in less than 10% of cases [22]. The refracture rate reported in the literature is less than 5%, but increases as bone deficit increases [23].

36.7.3 Foot Infections Diabetes frequently results in foot infections. About 20% of diabetic foot infections are complicated by the involvement of the underlying bone, which typically results from contiguous spreading from overlaying soft-tissue infection. This significantly raises the risk of lower extremity amputation. Deep wounds, peripheral neuropathy, Charcot’s arthropathy, vascular insufficiency, poor glycemic control, and immunological dysfunction are among the risk factors for diabetic foot osteomyelitis (Fig. 36.6). The choice of treatment is influenced by the presence of an associated vascular disorder and the presence of adjacent ulcers. Antibiotic treatment following debridement has demonstrated good outcomes in patients with good tissue oxygenation [24]. Pressure-off-loading surgical techniques such as hammertoe correction or Achilles tendon lengthening can help prevent ulcers and decrease their recurrence. If the extent of osteomyelitis requires larger resections, minor amputations (digit, trans metatarsal, and Chopart joint) may be opted for to continue to allow loading on the residual limb. Amputations below the knee or thigh may be considered in severe cases complicated by severe vascular insufficiency. Of great importance is the correct staging of the host (A, B, or C) and proper patient information.

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Fig. 36.6  Clinical and radiographic assessment of chronic osteomyelitis of the foot

36.8 Conclusions Osteomyelitis is a common clinical problem with an increased incidence correlated mainly with diabetes-related foot infections. Successful treatment depends on accurate diagnosis, correct staging of the disease and the host, and collaboration of multiple specialists. Antibiotic therapy is first line in the treatment of acute osteomyelitis, while it is adjuvant in the treatment of chronic disease in which surgery is still the gold standard.

References 1. Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med. 1997;336(14):999–1007. NEJM199704033361406. 2. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. N Engl J Med. 1970;282(4):198–206. NEJM197001222820406. 3. Cierny G, Mader JT.  Adult chronic osteomyelitis. Orthopedics. 1984;7(10):1557–64. https://doi. org/10.3928/0147-­7447-­19841001-­07. 4. McPherson EJ, Woodson C, Holtom P, Roidis N, Shufelt C, Patzakis M. Periprosthetic total hip infec-

tion: outcomes using a staging system. Clin Orthop Relat Res. 2002;403:8–15. 5. Klosterhalfen B, Peters KM, Tons C, Hauptmann S, Klein CL, Kirkpatrick CJ.  Local and systemic inflammatory mediator release in patients with acute and chronic posttraumatic osteomyelitis. J Trauma. 1996;40(3):372–8. https://doi. org/10.1097/00005373-­199603000-­00008. 6. Brodie B.  Pathological and surgical observations on the diseases of the joints. Washington: D. Green; 1834. 7. Jennin F, Bousson V, Parlier C, Jomaah N, Khanine V, Laredo J-D. Bony sequestrum: a radiologic review. Skelet Radiol. 2011;40(8):963–75. https://doi. org/10.1007/s00256-­010-­0975-­4. 8. Baumert N, von Eiff C, Schaaff F, Peters G, Proctor RA, Sahl H-G. Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants. Microb Drug Resist. 2002;8(4):253–60. https://doi. org/10.1089/10766290260469507. 9. Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM. Microbial biofilms. Annu Rev Microbiol. 1995;49:711–45. annurev.mi.49.100195.003431. 10. Jacobson IV, Sieling WL.  Microbiology of secondary osteomyelitis. Value of bone biopsy. S Afr Med J. 1987;72(7):476–7. 11. Fleischer AE, Didyk AA, Woods JB, Burns SE, Wrobel JS, Armstrong DG.  Combined clinical and laboratory testing improves diagnostic accuracy for osteomyelitis in the diabetic foot. J Foot Ankle Surg. 2009;48(1):39–46. jfas.2008.09.003.

36 Osteomyelitis 12. Ertugrul BM, Savk O, Ozturk B, Cobanoglu M, Oncu S, Sakarya S.  The diagnosis of diabetic foot osteomyelitis: examination findings and laboratory values. Med Sci Monit Int Med J Exp Clin Res. 2009;15(6):CR307–12. 13. Shahid M, Holton C, O’Riordan S, Kraft JK. Sonography of musculoskeletal infection in children. Ultrasound. 2020;28(2):103–17. 10.1177/1742271X20901736. 14. Fayad LM, Carrino JA, Fishman EK. Musculoskeletal infection: role of CT in the emergency department. Radiographics. 2007;27(6):1723–36. https://doi. org/10.1148/rg.276075033. 15. Xu Z, Koo A, Shah A. The utility of MRI for the diagnosis of osteomyelitis in the pressure ulcer patient. J Plast Reconstr Aesthetic Surg. 2017;70(2):289–91. 16. Casali M, Lauri C, Altini C, et al. State of the art of (18)F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation. Clin Transl imaging. 2021;9(4):299–339.­021-­00445-­w. 17. Senneville E, Lombart A, Beltrand E, et  al. Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study. Diabetes Care. 2008;31(4):637–42. https://doi. org/10.2337/dc07-­1744. 18. Simpson AH, Deakin M, Latham JM, Chronic osteomyelitis. The effect of the extent of surgical resection on infection-free survival. J Bone

413 Joint Surg Br. 2001;83(3):403–7. https://doi. org/10.1302/0301-­620x.83b3.10727. 19. Masquelet AC, Fitoussi F, Begue T, Muller G. Reconstruction des os longs par membrane induite et autogreffe spongieuse. Ann Chir Plast Esthet. 2000;45(3):346–53. 20. Morelli I, Drago L, George DA, Gallazzi E, Scarponi S, Romanò CL.  Masquelet technique: myth or reality? A systematic review and meta-analysis. Injury. 2016;47:S68–76. S0020-­1383(16)30842-­7. 21. Ilizarov GA.  Basic principles of transosseous compression and distraction osteosynthesis. Ortop Travmatol Protez. 1971;32:7. 22. Yin P, Ji Q, Li T, et  al. A systematic review and meta-analysis of Ilizarov methods in the treatment of infected nonunion of tibia and femur. PLoS One. 2015;10(11):1–12. pone.0141973. 23. Papakostidis C, Bhandari M, Giannoudis PV.  Distraction osteogenesis in the treatment of long bone defects of the lower limbs. Effectiveness, complications and clinical results; a sistematic review and meta-analysis. J Bone Jt Surg. 2013;95(B(12)):1673–80. 24. Pittet D, Wyssa B, Herter-Clavel C, Kursteiner K, Vaucher J, Lew PD.  Outcome of diabetic foot infections treated conservatively: a retrospective cohort study with long-term follow-up. Arch Intern Med. 1999;159(8):851–6. archinte.159.8.851.

Part VII Plastic Surgery: When and How

Grafting and Micrografting in Wound Care


Alberto Bolletta, Davide Di Seclì, Mirco Pozzi, and Emanuele Cigna

37.1 Introduction Chronic wounds represent a challenging problem and wound care is becoming of primary importance for plastic surgeons. Many strategies have been tested to treat chronic wounds, such as advanced wound dressings, negative-pressure wound therapy (NPWT), and surgical procedures, with good results in terms of enhancing the healing process. The use of autologous skin grafts, either full thickness or split thickness, represents a valuable option in wound healing, even though the extension of donor sites is limited. Allograft and xenograft, but also tissue-engineered artificial skin, provide prompt but temporary coverage. An ideal graft should be immediately available, non-­ immunogenic, permanent, and associated with low morbidity [1]. As previously stated, autologous skin grafts represent a good choice in wound care, as they are immediately available and non-immunogenic, but donor areas for skin grafts are limited, even when meshing techniques are used. The use of micrografts, on the other side, offers all the aforementioned characteristics as it is autologous tissue, immediately available for

coverage, which uses a minimal amount of donor skin [1].

37.2 Skin Grafts 37.2.1 History Skin grafting is an important technique in reconstructive surgery, being an essential procedure in patients who have suffered burns, traumas, and non-healing or large wounds. It was first described in India approximately 3000 years ago, where full-thickness grafts harvested from the gluteal region were used for nasal reconstruction after amputation. The use of this surgical technique was introduced in Europe in the nineteenth century: in 1817, Sir Astley Cooper used a full-thickness skin graft from an amputated thumb to provide coverage for the remaining stump. In 1823, Buenger performed a successful nasal reconstruction using a skin graft. In 1874, a full-­ thickness skin grafting procedure was published by Wolfe and made popular by Krause, so the technique became known as Wolfe-Krause [2].

37.2.2 Classification A. Bolletta (*) · D. Di Seclì · M. Pozzi · E. Cigna Unit of Plastic Surgery and Microsurgery, University of Pisa, Pisa, Italy

A skin graft consists of the entire epidermis with a dermal component of variable thicknesses. If

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



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ing the type of graft. When harvesting a splitthickness skin graft, the donor site heals by secondary intention, whereas the harvest of a full-thickness graft requires a primary closure of the donor site. Therefore, the amount of skin needed and the healing process of the donor site should be taken into consideration: if a larger skin graft is required, a split-thickness skin graft would probably be the best choice. Moreover, a split-­thickness skin graft can be expanded via meshing techniques. Another aspect to consider is the fact that thicker skin grafts have a greater metabolic demand on the Fig. 37.1  Manual dermatome is used to harvest split-­ wound bed during healing. Thus, it is advisable thickness skin grafts to choose split-thickness grafts in the management of chronic wounds [4]. the entire thickness of the dermis is included, the graft is known as full-­thickness skin graft (FTSG). If not, the graft is referred to as a split-thickness 37.2.3 Meshing Techniques skin graft (STSG). STSGs are then classified as thin (0.005–0.012 Meshing techniques can be used to expand the in), intermediate (0.012–0.018 in), or thick surface of the skin graft. Many techniques have (0.018–0.030 in), based on the thickness of the been described: from a manual incision of the graft [3] (Fig. 37.1). skin graft using a scalpel blade (No. 11) to a The choice between a split- or full-thickness hand-powered meshing device (mesher). The use skin graft for wound coverage depends on many of meshers is the most common and preferred factors, including contraction, location of the technique. The mesher applies multiple slits at wound, type of wound, and size of the graft. regular intervals on the skin graft and in preset Contraction represents an important factor in ratios. Commonly used ratios include 1:1, 2:1, the healing process of skin grafts. Primary con- 3:1, and even 6:1. (Fig. 37.2) Once meshed, the traction is caused by elastin fibers within the der- skin grafts can be stretched, increasing the area mis and occurs immediately after harvesting. The of coverage. The higher the meshing ratio, the amount of primary contraction that a graft experiences is proportional to the amount of dermis in the graft; therefore full-thickness skin grafts exhibit more primary contraction than split-­ thickness ones. Secondary contraction is a process that occurs during graft healing and its rate is higher in grafts with a thinner dermal component. Secondary contraction can cause significant limitations in the stretch and mobility of the graft; therefore, full-thickness grafts are the first choice in specific areas such as joint surfaces. After healing, grafts with a thicker dermal layer are more resistant to subsequent trauma. The size of the graft needed is another Fig. 37.2  A meshed split-thickness skin graft is used to important parameter to consider before choos- cover a large skin defect

37  Grafting and Micrografting in Wound Care

Fig. 37.3 Dressing over meshed split-thickness skin graft with hyaluronic acid gauze

larger the area of the wound that can be covered. But a higher ratio is also related to a longer healing time, due to the reduced area of the wound covered by the meshed skin grafts. In meshed skin grafts, in fact, holes are formed within the graft between thin skin bridges, from which the epithelialization process will start. These holes allow fluid drainage, preventing blood or serum accumulation between the recipient wound bed and the graft, which could cause graft failure [3, 5] (Fig. 37.3).

37.2.4 Preparation of the Wound Bed The characteristics of the wound bed are of primary importance in the healing process of the skin grafts. To avoid failure of the procedure, surgeons must prepare a suitable wound bed. Debridement of the wound bed can be performed using different techniques, such as the scalpel, the dermatome, or the hydrosurgery device until the wound bed shows a healthy bleeding tissue. Nonviable tissue must be removed also from the wound edges. If the wound bed is not clean, the skin graft cannot undergo the normal healing process [6]. NPWT can be used to prepare the wound bed before skin graft application, and also on the skin graft to improve its survival (Fig.37.4).


Fig. 37.4  The possibility of applying negative-pressure wound therapy over the skin graft in order to improve graft survival

37.2.5 Indications for the Use of Skin Grafts Skin grafting is a fundamental element of reconstructive procedures. It is usually performed when a simpler method of wound closure, such as secondary wound healing or primary closure, is not indicated [5–7]. The use of skin grafts is a safe and simple procedure in patients with large wounds that would otherwise be difficult to treat. Reestablishing skin continuity is essential to prevent infections and reduce fluid loss, as well as allowing the patient to return to everyday activities. Split-thickness skin grafting is the current gold standard for the treatment of traumatic losses of skin, especially in burn injuries [8, 9]. In fact, the use of skin grafts is associated with reduced wound contraction and extracellular matrix deposition, compared to non-grafted full-­ thickness wounds [10]. Requirements for skin grafting include an available donor site and a recipient site that is well-vascularized and clean. Typically, skin grafts are used to cover deep partial-­thickness skin defects and full-thickness skin defects, or can be placed directly over muscles. However, skin grafts can potentially survive on any wound bed with good vascularization, including tendon with intact paratenon (forearm, hand, fingers), cartilage with intact perichon-


drium (ears), and bone with intact periosteum (skull). On the other hand, if vascularized tissue in the wound bed is absent, the grafting procedure will fail [7].

37.2.6 Contraindications Contraindications to the use of skin grafts are limited. Active infection, active bleeding, and persistence of cancer are absolute contraindications to a skin grafting procedure. Also, wounds with exposed bone, tendons, nerves, or blood vessels without appropriate coverage by a vascularized tissue represent a contraindication to the use of skin grafts. The location of wounds over joints or key anatomical areas, in which contraction could reduce mobility and/or aesthetic appearance (i.e., wrist, elbow, eyelid), can be considered as relative contraindications. Surgeons should consider individual factors such as tobacco use, chronic steroid use, malnutrition, or previous radiotherapy on a case-by-­ case basis [10].

37.2.7 Epidermal Grafts The harvest of a split-thickness skin graft determines a variable donor site morbidity, as the donor site usually heals by secondary intention, and the process may take a longer time, with a risk of infection and hypertrophic scarring. Epidermal grafting (EG) is an alternative method of autologous skin grafting which requires the harvesting of only the epidermal layer of the skin. Dermatologists first used epidermal grafting in 1964 and subsequently for the treatment of hypopigmented lesions. EG is obtained by applying continuous negative pressure on the normal skin to raise blisters [11]. The roof of the blister, which is the epidermis, is then excised and transferred onto the wound. As the dermis in the donor site remains intact, the skin regenerates without scars. This procedure is also painless as the pain fibers in the dermis are unstimulated, allowing autologous skin grafting in the outpatient setting without the

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administration of anesthesia and with minimal donor site morbidity [12]. The epidermal grafts are commonly used to treat chronic wounds. EG promotes wound healing by expressing growth factors that accelerate wound healing and the migration of cells from the wound edges [11].

37.2.8 Wound Healing and Fat Graft Chronic wounds are one of the most challenging conditions for plastic surgeons and have been a topic of great interest in the field of regenerative medicine for years. Recently, the focus of regenerative medicine has moved to fat grafting as a healing procedure, being able to promote faster wound closure and pain reduction. In reality, free fat graft autotransplantation is an old topic in plastic surgery: since the nineteenth century, fat grafting has been used in the treatment of a variety of soft-tissue defects. An important role in the healing process was given to a “fibroblast-like” cell of mesenchymal origin, called pre-adipocyte, which was able to differentiate in adult adipocytes when replanted [13]. An important breakthrough in this field was given by Coleman in the late 90 s, who described the principal technique to harvest an adequate amount of fat tissue able to guarantee its survival after grafting [14] (Fig. 37.5). During the last 15 years, scientific investigations on the use of fat tissue as a bioactive material through fat grafting or micro/nano-fat techniques have significantly increased, gaining an important role in wound treatment. Nowadays it is known that most fat graft regenerative capacity depends on the autologous adipose-derived mesenchymal stem cells (AD-MSCs), typically suspended in the stromal vascular fraction (SVF) of fat tissue. AD-MSCs have a multi-potent differentiation potential and can proliferate and differentiate into skin cells (endothelial cells, dermal fibroblasts, and keratinocytes) and mediate tissue regeneration and wound healing, via paracrine and autocrine pathways [15]. The biological properties and the capability of AD-MSCs to differentiate and interfere with the

37  Grafting and Micrografting in Wound Care

Fig. 37.5  Decantation after fat graft harvesting. The separation of fat components is noted: blood and fluids are located on the lower part of the syringe, while the upper part is mainly composed of fat

wound healing process are modulated by the microenvironment of the tissue, through the action of different cytokines: AD-MSCs act on amplifying fibroblasts, macrophages, and skin cells via the secretion of growth factors (TGF-β and GDF11) and on promoting cell proliferation and angiogenesis via VEGF, PDGF, and IGF.  TGF-β plays the most important role by activating ADSCs’ differentiation, increasing their ECM secretion, regulating melanin production, and more importantly, promoting the upregulation of GDF11, involved in accelerating skin cell production and maturation after injury. Moreover, in association with MMP-9, TGF-β plays a key role in remodeling and wound closure [16]. Multiple studies have verified the role of autologous fat grafting as a procedure for the treatment of diabetic foot: infiltrations along the edges and the wound bed have shown an improvement in the depth and size of the ulcers, and also


an improvementin the surrounding skin conditions [17, 18]. On the same topic, further studies demonstrated how the application of platelet gel combined with centrifuged fat tissue in sequential treatments can restore the superficial characteristics of the injured tissues [19]. Repeated sessions of fat grafting may also improve dermal scars and keloids, resulting from traumatic injuries or severe burns: collected data suggest that fat grafting promotes epidermal cell proliferation associated with an improvement in the structure of ECM (new collagen disposition and increased vascularisation) and trophism of the local tissue, which results in remodeling of the scar tissue toward the quality of normal skin [20–22]. Moreover, recent studies have further analysed the role of the ultrafiltered fat graft injected in chronic wounds in reducing pain: through the secretion of growth factors that create a favouable microenvironment, it seems that nerve regeneration is stimulated, with a resultant reduction of pain and improvement in the patient’s quality of life [23] (Fig. 37.6). Data available so far suggest a non-inferior role of fat grafting compared to the standard treatment of chronic wound healing. However, further studies are needed in order to better evaluate the action of fat grafting and to define standard protocols of treatment.

Fig. 37.6  Fat grafting in small aliquots into perilesional skin promotes healing of a vascular ulcer of the lower limb

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37.3 History and Development of Micrografting Technique The first method of grafting small pieces of skin was first described by Jacques-Louis Reverdin in 1869 [1]. His method consisted of grafting small, full-thickness pieces of skin to promote wound healing. These little islands of skin would promote healing and epithelization of the wound. The concept is that, by creating small skin islands within the wound, a large area of the wound bed comes in contact with an epithelial surface, promoting epithelial migration between micrograft islands. Since then, various techniques have been developed, with many advantages and disadvantages, but nowadays the Meek technique represents the most popular and used technique of harvesting micrografts.

skin graft, from one-sixth to one-ninth the size of the wound, placing the dermis up on a sheet of sticky paper and then cutting it into strips. After that, the skin graft is placed on another sheet of paper and cut again horizontally into small squares. This technique introduced the concept of using a sheet of paper to help placing the skin graft on the wound bed in a more uniform manner. Eventually, also the use of this technique was gradually abandoned with the advent of meshed skin grafts.

37.3.3 The Intermingled Technique

The intermingle technique is a procedure used to cover extended burn wounds when skin donor sites are limited. It was introduced in the early 80 s. The procedure involves using allografts and autografts together. The surgical technique consists of wrapping the wound with allografts and then punching them, creating holes of about 37.3.1 The Pinch Graft 1 cm. After that, autografts are harvested and cut 2 The pinch graft by Jacques-Louis Reverdin into 0.25  cm pieces and placed into the holes (1869) represents the first attempt at micrograft- created in the allografts. The procedure and healing process induced by ing. It involves harvesting small pieces of skin, only the epidermis, and applying them on the the intermingled grafts were later studied by wound bed, allowing epithelization from the Yang et al. [24] and a particular phenomenon was documented: the “sandwich phenomenon.” This edges of the skin grafts and of the wound [1]. Pinch grafts were widely used for treating phenomenon is characterized by the migration of chronic leg ulcers, but after the rise of split-­ the autograft in between the allograft dermis and thickness skin grafts, this technique was gradu- epidermis. After the migration, the allograft degenerates, thanks to the endogenous process of ally abandoned. This technique offers a simple and low-cost rejection, leaving the autograft intact, thus allowstrategy in wound healing, resistant to infections ing, during the healing process, the protection of and pressure, especially when the skin grafts are the autograft. This procedure demonstrates less harvested full-thickness, but it is associated with contractures of the skin graft compared to the a poor cosmetic result, due to the uneven disposi- other techniques, but it can be tedious and it can tion of the skin islands, and to the disadvantage be associated with the rejection of the skin graft, of a donor site that cannot be used again for due to the use of allografts. future grafts.

37.3.4 Microskin Graft 37.3.2 Patch/Postage Stamp Graft Another attempt at developing a micrograft technique was made by Gabarro in 1943. His technique, known as patch graft, consisted of using a

The microskin graft is a micrografting technique developed by Zhang and co-workers [25–27]. It involved the use of allograft and autograft, incorporating the theories behind the patch and the

37  Grafting and Micrografting in Wound Care

intermingled grafting. In this technique, after harvesting the autograft, it is cut with scissors into small pieces, smaller than 1  mm3 and then immersed in a saline solution, which theoretically allows the grafts to orient themselves with their epidermal sides facing upwards. After that, the skin grafts are put on a silk cloth and, lastly, on a sheet of split-thickness allograft overlayed on the silk cloth. The combined skin graft (minced autograft and the sheet of allograft) is allowed to dry for a certain period of time before being transferred to the wound bed. The small pieces of autograft are placed on the wound bed without any regard for the orientation, because, in the authors’ opinion, the skin grafts are so small that they still have their dermal appendages in contact with the wound bed, even if they are placed with their dermal side up. Although the technique is easy to perform, cost-efficient, and provides resistance to infection and to trauma; it is associated with an increased rate of contracture [28]; and to an uneven orientation of the skin graft.

37.3.5 Microscopic Split-Skin “Diced” Graft The microscopic split-skin graft, also known as diced graft, is a peculiar technique of harvesting skin graft developed by Blair and co-workers [29] with the particularity of creating an expansion ratio up to 26:1. The technique involves the use of a histological tissue slicer that creates diced graft of 200 μm2 in surface. Then the diced grafts are spread into the wound bed with a knife and covered with a hydrocolloid dressing. A positive aspect of this technique is represented by its possible and theoretical use in outpatient settings.

37.3.6 Fine-Particle Graft (Autologous Skin Suspension) The autologous skin suspension represents a controversial technique of historical interest, originally described by Najarian and McCorkle [30,


31]. In this technique, a sheet of split-thickness skin graft was reduced into small pieces with a blender and then applied onto the wound bed of an animal model (rabbit). It was applied, without any difference in outcome, on granulation tissue, fascia, or denudes skin and it demonstrated a complete epithelization in 92.5% of the rabbits, but hyperplastic, hyperkeratotic, and contractions of the scars were noted, with poor cosmetical results.

37.3.7 Micrograft Spray This technique is an innovative method which involves spraying micrografts onto the wound bed after cutting the skin graft into pieces of 0.2– 0.5  mm in size, with a final expansion of 110–150:1. This technique showed a reduction of wound healing time compared to conventional microskin grafting (29.7 days vs 37.3 days, p 30% TBSA) and where the donor site for harvesting skin grafts is not available [33]. Often, the expansion ratio required is more than 1:6 and this kind of expansion cannot be

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reached with meshed skin graft. The limitations of meshed grafts, due to the discrepancy between the theoretical expansion rate and what is actually obtained after the procedure (probably due to the shrinking of STSG and its elasticity) [35], have raised the interest in the Meek Micrografting technique. According to a study by Kok et al. comparing the “mesh” with the “Meek” technique, patients treated with the latter underwent fewer surgeries (10 vs 19.75), had a shorter length of hospital stay (51 vs 120.5  days), and less allograft used for TBSA% burn (115.7 cm2 vs 356.5 cm2), with an overall lower cost [36]. Moreover, a faster re-­ epithelialization and a higher viability rate are seen after the use of the Meek technique, compared to the mesh technique [36, 37]. Micrografting has a higher success on poor wound beds, with infection or a poor vascular supply. This is due to poor metabolic demand and a greater skin coverage expansion ratio (1:12). The disadvantage of the Meek technique includes a “polka dot” appearance once healed which is not seen in the mesh technique.

37.4.1 The Modified Meek Graft Procedure The Meek technique, as he published it in the 1950s, was later modified. The modified Meek technique was first published in 1993 by Kreis et  al. [33, 38]: it involves the harvesting of a split-­thickness skin graft which is placed, after being sprayed with a special glue, on a cork plate of 42 × 42 mm, dermal side down. Then, it is soaked with 0.9% saline solution and placed in a cutting machine that contains 13 circular blades. The cork plate passes through the machine which cuts the graft but not the cork plate. After this first step, the cork plate is rotated 90° and passes again through the cutting machine. What is obtained is 196 square pieces (14 × 14) of the skin graft. The epidermal surface of the graft is then sprayed with a special glue and allowed to dry for 5–10 min. Then the cork plate is pressed onto a prefolded polyamide gauze on an aluminum foil backing into 14 × 14

square pleats. The cork plate is then gently removed, leaving the skin graft islands on the gauze. After that, the gauze is pulled from the four angles, until the pleats become completely unfolded and then the aluminum backing is removed, leaving the expanded gauze with separated autograft islands ready for grafting. The gauze is then applied, side down, on the wound bed and secured with staples. It is removed only after six days when the grafts have grown sufficiently into the wound bed. After removal, the wound bed with the skin islands is covered with non-adherent sheeting to prevent any movement during daily dressing changes, which continue daily until re-epithelialization is completed. The healing process in the micrografting procedure is driven by the proliferation and migration of the keratinocytes. Micrografts of a certain size (0.8 × 0.8 mm) initially survive by the diffusion of fluid from the wound bed rather than neovascularization [33].

37.5 Fields of Application of Micrografts 37.5.1 Burns Major burns represent dangerous injuries associated with high disability and mortality. Survival rates in major burns in low- and middle-income countries are compromised by a deficit of autograft donor skin to obtain definitive wound coverage [39]. The principal treatment of burns is the timely removal of necrotic tissue and effective wound closure, but usually, when burns are extended, there is a lack of autologous skin. Burn environment, in fact, is suitable for bacteria growth and the necrotic tissue in the wound tends to stimulate the production of a variety of inflammatory mediators, which can cause many complications (internal disorders, wound infection, shock). In this case, prompt debridement and skin grafting to achieve wound healing reduce the risk of infection and help maintain the organ function, improving the outcomes [40].

37  Grafting and Micrografting in Wound Care

Standard meshed grafts require the presence of approximately an equal surface of the donor site to cover the burn wound and some sites are inappropriate as donor sites (face and hands). In this scenario, the use of the Meek micrografting technique offers an alternative to cover large areas in the absence of other forms of coverage. It is a reliable method to achieve wound healing, reaching greater expansion ratio compared to meshed skin grafts. The technique has been recently readopted and its use in burn wound healing is of primary importance especially when TBSA >30% and in children. The use of this technique and its fields of application have been studied by many authors. A retrospective study by G. Hu et al. evaluated the efficacy of the two-stage Meek micrografting technique comparing it with the one-stage procedure in patients with severe burns. In this study, prompt micrografting after an early debridement was compared with delayed micrografting after several days (3–5) of early debridement and the results showed a significantly higher survival rate of the two-stage Meek grafting than that of the one-stage group. In the authors’ opinion, this is due to a more adequate resuscitation in the two-­ stage micrografting group, which contributes to better wound preparation and higher levels of serum protein and albuminemia. Many factors can affect the survival of Meek micrografting in burn wounds. Zhang et al. demonstrated that the burn severity index, Meek skin graft area, duration of anesthesia, pre-operative nutrition status, and post-operative infections are important factors affecting the survival of micrografting. Albumin should be maintained at a high level, infection should be actively controlled, especially in the first 1–3 days after surgery and operation time should be shortened as much as possible [41].

37.5.2 Chronic Wounds Chronic wounds can be defined as wounds with multifactorial pathogenesis that do not follow the normal healing process, remaining unhealed for


at least 12  weeks [42]. The healing process in these wounds is completely different from acute healing, as it underlies cellular dysfunction and abnormal prolongation of inflammatory and proliferative stages of healing [43]. Among chronic wounds, non-healing ulcers, especially venous ulcers in the lower extremity, occur very frequently [44]. The role of micrografts in the treatment of ulcers has been demonstrated in several studies, in which micrografts promoted the healing of chronic leg ulcers of different etiologies, including venous, diabetic, and post-traumatic ulcers [44]. In treating chronic wounds, the micrografting procedure can be used as an option, as it was effective and less invasive than main grafting procedures [1]. A particular technique of skin micrografting preparation has the objective of disaggregating, in a mechanical way, autologous tissue, obtaining pieces of skin of 80  μm. This approach allows also the collection of autologous micrografts enriched in progenitor cells, growth factors, and particles of extracellular matrix derived from the patient’s own tissue [44]. In vitro studies have demonstrated that micrografts obtained mechanically by selecting particles with a cut-off of 80  μm show positive results for MSC markers such as CD73, CD90, CD115, and CD146 and negative results for hematopoietic markers such as CD34 and CD45. These data support the regenerative potential of micrografts, and several studies have reported the ability of micrografts to differentiate into chondrocytes, osteocytes, and adipocytes [45–48]. In vitro studies have shown that micrografts exhibit a fibroblast-like morphology when cultured, and have confirmed the expression of MSC markers. When combined with collagen sponges, micrografts can form a viable and proliferative bio-complex, enhancing their regenerative potential [49] and this is one advantage of using a micrograft suspension. Micrografts obtained by mechanical disaggregation of autologous tissue have also been widely used in the management of post-surgical dehiscence. Post-surgical wound dehiscence can arise as a complication in different types of procedures, such as the transplantation of the lung and

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kidney, colon resection, following a laparotomy procedure with an incidence of about 0.5% and gynecological procedures, such as Caesarean section and total abdominal hysterectomy with an incidence of 15%. Orthopedic surgical complications can lead to longer hospitalization, increased patient morbidity, and higher costs. Different studies showed the effectiveness of treatment with autologous micro-grafts in ameliorating the healing of post-­ surgical orthopedic dehiscence in patients who previously underwent a primary surgical intervention, such as tibial-tarsal fracture and ­ forefoot alignment, offering an efficient and promising alternative to the already existing approaches, to improve wound healing in patients who exhibit wounds hard to heal. Another advantage, with respect to NPWT, is the fact that it does not require dressing changes at 48 or 72 h. In fact, the application of micro-grafts is performed only once without particular precautions or other dressings for the patient [50].

37.5.3 Treatment of Scars Hypertrophic scars and keloids are aberrant expressions of pathological wound healing with an excess of extracellular matrix (ECM), mainly driven by fibroblasts. Keloids and hypertrophic scars pose a clinical challenge in scar-related cosmetic dysfunctions and are highly prevalent in trauma and burns. In the treatment of pathological scars, several methods have been implemented to improve hypertrophic scars using both surgical and nonsurgical approaches. The use of corticosteroids, laser therapy, 5-fluoruracil, botulin toxin A, and Interleukin-10 are some examples. However, identifying an optimal universal treatment for all types of scars still remains a challenge. Moreover, in the treatment of scars, autologous micrografts can be a new approach. A study by Svolacchia et  al. demonstrated the potential efficacy of dermal autologous micrografts, used alone, to treat hypertrophic and keloid scarring as a result of burns or traumatic injuries [51]. The authors suggest that the effectiveness of dermal

micrografts could be related to the immunomodulatory effect of MSCs, which secrete a combination of growth factors and cytokines to promote wound repair. In fact, the combination of growth factors and cytokines successfully induces angiogenesis, reduces inflammation, and promotes fibroblast migration and collagen production.

References 1. Biswas A, Bharara M, Hurst C, Armstrong DG, Rilo H.  The micrograft concept for wound healing: strategies and applications. J Diabetes Sci Technol. 2010;4:808–19. 2. Hauben DJ, Baruchin A, Mahler D. On the history of the free skin graft. Ann Plast Surg. 1982;9:242–6. 3. Adams DC, Ramsey ML. Grafts in dermatologic surgery: review and update on full- and split-thickness skin grafts, free cartilage grafts, and composite grafts. Dermatol Surg. 2006;31:1055–67. 4. Lindenblatt N, Calcagni M, Contaldo C, Menger MD, Giovanoli P, Vollmar B.  A new model for studying the revascularization of skin grafts in vivo: the role of angiogenesis. Plast Reconstr Surg. 2008;122:1669–80. 5. Elseth A, Lopez ON. Wound grafts. Treasure Island, FL: StatPearls Publishing; 2023. https://pubmed.ncbi. 6. Oosthuizen B, Mole T, Martin R, Myburgh JG.  Comparison of standard surgical debridement versus the VERSAJET plus™ hydrosurgery system in the treatment of open tibia fractures: a prospective open label randomized controlled trial. Int J Burns Trauma. 2014;4:53. pmc/articles/PMC4212881/. Accessed 22 Jul 2022. 7. Janis JE, Kwon RK, Attinger CE.  The new reconstructive ladder: modifications to the traditional model. Plast Reconstr Surg. 2011;127:205S. https:// 8. Brusselaers N, Pirayesh A, Hoeksema H, Richters CD, Verbelen J, Beele H, Blot SI, Monstrey S. Skin replacement in burn wounds. J Trauma. 2010;68:490–501. 9. Profyris C, Tziotzios C, Do Vale I.  Cutaneous scarring: pathophysiology, molecular mechanisms, and scar reduction therapeutics. J Am Acad Dermatol. 2012;66:1–10. 10. Earlc P.  Skin grafting and the “Hree-quarter”thickness skin graft for prevention and correction of Cicatricial, formation. Ann Surg. 1941;113:1034–49. 11. Gabriel A, Sobota RV, Champaneria M. Initial experience with a new epidermal harvesting system: overview of epidermal grafting and case series. Surg Technol Int. 2014;25:55–61. https://www.ncbi.nlm. 12. Hachach-Haram N, Bystrzonowski N, Kanapathy M, Smith O, Harding K, Mosahebi A, Richards T. A prospective, multicentre study on the use of epidermal

37  Grafting and Micrografting in Wound Care grafts to optimise outpatient wound management. Int Wound J. 2016;14:241–9. 13. Billings E, May JW.  Historical review and present status of free fat graft autotransplantation in plastic and reconstructive surgery. Plast Reconstr Surg. 1989;83:368–81. 14. Coleman SR.  Long-term survival of fat transplants: controlled demonstrations. Aesthet Plast Surg. 1995;19:421–5. 15. Gentile P, Sterodimas A, Calabrese C, Garcovich S. Systematic review: advances of fat tissue engineering as bioactive scaffold, bioactive material, and source for adipose-derived mesenchymal stem cells in wound and scar treatment. Stem Cell Res Ther. 2021;12:318.­021-­02397-­4. 16. Mazini L, Rochette L, Admou B, Amal S, Malka G.  Hopes and limits of adipose-derived stem cells (adscs) and mesenchymal stem cells (mscs) in wound healing. Int J Mol Sci. 2020;21:1306. 17. Stasch T, Hoehne J, Huynh T, De Baerdemaeker R, Grandel S, Herold C.  Débridement and autologous lipotransfer for chronic ulceration of the diabetic foot and lower limb improves wound healing. Plast Reconstr Surg. 2015;136:1357–66. 18. Luu CA, Larson E, Rankin TM, Pappalardo JL, Slepian MJ, Armstrong DG. Plantar fat grafting and tendon balancing for the diabetic foot ulcer in remission. Plastic and Reconstr Surg. 2016;4:e810. https:// 19. Cervelli V, Gentile P, Grimaldi M. Regenerative surgery: use of fat grafting combined with platelet-rich plasma for chronic lower-extremity ulcers. Aesthet Plast Surg. 2009;33:340–5. 20. Maroesjka Spiekman | MD/phd-student | MD, Phd researchgate. Maroesjka-­Spiekman. 21. Klinger M, Marazzi M, Vigo D, Torre M. Fat injection for cases of severe burn outcomes: a new perspective of scar remodeling and reduction. Aesthet Plast Surg. 2008;32:465–9. 22. Nicoletti G, Brenta F, Jaber O, Laberinti E, Faga A. Lipofilling for functional reconstruction of the sole of the foot. Foot. 2014;24:21–7. 23. Cuomo R, Giardino FR, Nisi G, Han J, Diluiso G, Tresoldi MM, Pieretti G, Brandi C, Grimaldi L.  Fat graft for reducing pain in chronic wounds. Wound Repair Regen. 2020;28:780–8. 24. Chih-Chun Y, Tsi-Siang S, Te-An C, Wei-Shia H, Shou-Yen K, Yen-Fei C. The intermingled transplantation of auto- and homografts in severe burns. Burns. 1980;6:141–5. 25. Ming-liang Z, Zhi-de C, Xun H, Ming Z. Microskin grafting. I.  Animal experiments. Burns. 1986;12:540–3. 26. Ming-liang Z, Chang-yeh W, Zhi-de C, Da-xin C, Xun H. Microskin grafting. II. Clinical report. Burns. 1986;12:544–8. 27. Zhang M-L, Chang Z-D, Wang C-Y, Fang C-H. Microskin grafting in the treatment of extensive burns. J Trauma. 1988;28:804–7.

427 28. Yeh FL, Yu GS, Fang CH, Carey M, Alexander JW, Robb EC.  Comparison of scar contracture with the use of microskin and Chinese-type intermingled skin grafts on rats. J Burn Care Rehabil. 1990;11:221–3. 29. Blair S.  Microscopic split-skin grafts: a new technique for 30-fold expansion. Lancet. 1987;330:483–4. 30. Najarian JS, Mccorkle HJ. Experimental grafting of a suspension of skin particles. Surg Forum. 1957;30:43. 31. Najarian JS, Crane JT.  An experimental study of the grafting of a suspension of skin particles. Plast Reconstr Surg. 1957;20:342. 32. Xie W, Wang L, Tan H, Wang D, Liu J, Hu B, Huang W, Ren S, Sun K. Microskin grafting by spraying in burn management. Chin J Burns. 2002;18(1):26–8. 33. Quintero EC, Machado JF, Robles RA. Meek micrografting history, indications, technique, physiology and experience: a review article. J Wound Care. 2018;27:S12. sup2.s12. 34. Ottomann C, Hartmann B, Branski L, Krohn C. A tribute to Cicero Parker meek. Burns. 2015;41:1660–3. 35. Peeters R, Hubens A.  The mesh skin graft—true expansion rate. Burns. 1988;14:239–40. 36. Kok YO, Chong SJ, Liang WH, Tan BK, Tan KC.  Revolutionizing major burns management with micrografting—improved healthcare costs, time and burns resources. Plast Reconstr Surg. 2015;136:64. 37. Hackl F, Bergmann J, Granter SR, Koyama T, Kiwanuka E, Zuhaili B, Pomahac B, Caterson EJ, Junker JP, Eriksson E.  Epidermal regeneration by micrograft transplantation with immediate 100-fold expansion. Plast Reconstr Surg. 2012;129:443e. 38. Kreis RW, Mackie DP, Vloemans AWFP, Hermans RP, Hoekstra MJ.  Widely expanded postage stamp skin grafts using a modified meek technique in combination with an allograft overlay. Burns. 1993;19:142–5. 39. Rode H, Martinez R, Potgieter D, Adams S, Rogers AD.  Experience and outcomes of micrografting for major paediatric burns. Burns. 2017;43:1103–10. 40. Hu G, Zhang P, Chen Y, Yuan Z, Song H. Efficacy of two-stage meek micrografting in patients with severe burns. J Burn Care Res. 2021;43:1081. https://doi. org/10.1093/jbcr/irab241. 41. Zhang P, Wang W, Hu G, Yuan L, Ma S, Luo J, Song H, Huang Y, Xiang F.  A retrospective study of factors influencing the survival of modified meek micrografting in severe burn patients. J Burn Care Res. 2020;42:331–7. 42. Mustoe TA, O’ Shaughnessy K, Kloeters O. Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg. 2006;117:35S. prs.0000225431.63010.1b. 43. Ennis WJ, Meneses P.  Wound healing at the local level: the stunned wound. Ostomy Wound Manage. 2000;46:39S. https://pubmed.ncbi.nlm.nih. gov/10732639/.

428 44. Astarita C, Arora CL, Trovato L. Tissue regeneration: An overview from stem cells to micrografts. J Int Med Res. 2020;48:030006052091479. 45. Zanzottera F, Lavezzari E, Trovato L, Icardi A, Graziano A.  Adipose derived stem cells and growth factors applied on hair transplantation. Follow-up of clinical outcome. J Cosmet Dermatol Sci Appl. 2014;04:268–74. 46. Purpura V, Bondioli E, Graziano A, et al. Tissue characterization after a new disaggregation method for skin micro-grafts generation. J Vis Exp. 2016;109:e53579. 47. Monti M, Graziano A, Rizzo S, Perotti C, Del Fante C, d'Aquino R, Redi CA, Baena RRY.  In vitro and in  vivo differentiation of progenitor stem cells obtained after mechanical digestion of human dental pulp. J Cell Physiol. 2016;232:548–55. 48. Senesi L, De Francesco F, Farinelli L, Manzotti S, Gagliardi G, Papalia GF, Riccio M, Gigante

A. Bolletta et al. A.  Mechanical and enzymatic procedures to isolate the stromal vascular fraction from adipose tissue: preliminary results. Front Cell Dev Biol. 2019;7:88. 49. De Francesco F, Graziano A, Trovato L, Ceccarelli G, Romano M, Marcarelli M, Cusella De Angelis GM, Cillo U, Riccio M, Ferraro GA. A regenerative approach with dermal micrografts in the treatment of chronic ulcers. Stem Cell Rev Rep. 2016;13:139–48. 50. Marcarelli M, Trovato L, Novarese E, Riccio M, Graziano A.  RIGENERA protocol in the treatment of surgical wound dehiscence. Int Wound J. 2016;14:277–81. 51. Svolacchia F, De Francesco F, Trovato L, Graziano A, Ferraro GA. An innovative regenerative treatment of scars with dermal micrografts. J Cosmet Dermatol. 2016;15:245–53.

Surgical Debridement in Wound Care


Stefano Bottosso, Silvia Pasquali, Riccardo Ricci, and Zoran M. Arnež

38.1 Introduction Wound bed preparation has been defined as “a changing paradigm that links treatment to the cause and focuses on three components of local wound care: debridement, wound-friendly moist interactive dressings and bacterial balance” [1]. The acronym TIME, created from this concept, was first published in 2003 [2]: • • • •

lution, this concept can be extrapolated in a more detailed pathway. In this chapter, we will focus on the D, the debridement, in particular the surgical one in order to differentiate this from the other types of debridement: autolytic, enzymatic, and mechanic.

38.2 Definition

T: Tissue nonviable or deficient. I: Infection/inflammation. M: Moisture balance. E: Epidermis, nonmigrating (later modified).

We can define debridement as the process of removing devitalized and/or contaminated tissue from a traumatic or infected lesion until the achievement of surrounding healthy tissue and also the removal of the foreign material that has The last component was then changed to E for become embedded in the wound. In particular, the edge of the wound, nonadvancing, or under- when talking about chronic wounds, debridemined because this is not necessarily related to a ment is the process of removing necrotic tissue problem of the migration of epidermal cells [3]. [5]. Debridement can be considered the first This concept then evolved to the acronym necessary step for the healing process because it DIME [4], where D stands for the Debridement is able to provide a good substrate for the subseof the nonviable tissue within the wound. The quent healing of the tissues [6]. In fact, the prespurpose was to underline the surgical action that ence of slough inhibits the migration of should be practised in order to support the re-­ epithelial cells and also hard eschar prevents epithelialization of a chronic wound. epidermal cell migration and epithelialization. Of course, the DIME approach is just a global In addition, devitalized or dead tissue can also concept that stresses the key points for chronic predispose the clinical infection of the wound wound management but, to reach a wound reso- because it provides an ideal environment for many microorganisms. Due to these reasons, the S. Bottosso · S. Pasquali · R. Ricci · Z. M. Arnež (*) removal of the devitalized tissue can be considPlastic Surgery Clinic, University of Trieste, ered the most effective method to stimulate the Trieste, Italy healing process [7]. e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,


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38.3 Surgical or Sharp Debridement We have to distinguish surgical debridement from sharp debridement.

38.3.1 Surgical Debridement Surgical debridement changes a chronic wound into an acute one and it is achieved, thanks to surgical techniques by the excision, sometimes also in an aggressive way, of all the dead or devitalized tissues. Surgical debridement can also involve the amputation of a necrotic digit as well as the opening of sinus tracts and wound pockets in order to drain pus or exudate [8, 9]. This procedure can be painful and extensive and requires a skilled surgeon. It is better performed in an operating theater under anesthesia. A local anesthesia directly infiltrated into the wound bed can be enough for some patients in case of smaller wounds. In others, it is better to use a regional anesthesia with a nerve block, spinal, or epidural anesthesia, or in the most extreme cases general anesthesia. We also have to consider that some patients may be insensitive if they have diabetic neuropathy, whereas other neuropathic patients may have hyperesthesia and may be hypersensitive [10]. An example of surgical debridement is portrayed in Fig. 38.1.

38.3.2 Sharp Debridement On the other hand, sharp debridement requires a particular equipment, this procedure can damage the blood vessels below and it also requires a skilled practitioner. Bleeding complications are more frequent in this practice, especially in those patients who take anticoagulant agents or with bleeding disorders or clotting abnormality. In such a case a ligature or a suture is required of the bleeding point but more often a local pressure may be sufficient, especially if combined with hemostatic dressing. Sharp debridement (or con-

Fig. 38.1  Example of surgical debridement in chronic ulcer of the foot

servative debridement) is a selective procedure that will not result in total debridement because it consists of the removal of loose avascular tissue by excising small quantities of dead or devitalized tissue by using scissors or scalpel in a clinical setting. So, for the purpose of obtaining an adequate result, many sessions of debridement are required. We also have to underline that it may not be easy to identify correctly the devitalized tissue, especially if there is a muscle at the base of the wound. In this case, it may be useful to remember the four “C”s: • • • •

color, contraction, consistency, capacity to bleed.

In these cases, it is better to limit or delay debridement and consider other procedures [11]. An example of sharp debridement of a leg ulcer can be seen in Fig. 38.2.

38  Surgical Debridement in Wound Care


Fig. 38.3  Example of debridement with Versajet

Fig. 38.2  Example of sharp debridement in leg ulcer

38.4 Instruments To perform an adequate debridement some instruments are mandatory: a high-quality scalpel with a blade size of 10 or 15 (both reusable or disposable), sharp scissors, and forceps that can hold and grasp necrotic tissue. In addition, a probe can be useful to check the depth and the track of the wound [9]. Curettes can be useful to scrape small cavities, bone, or granulation tissue. Other, more sophisticated, instruments that can be used for surgical debridement are Hydrocision, Versajet ® (Smith-Nephew, Hull, UK), and the Ultrasound system [12, 13]. Hydrocision is particularly useful for soft tissue debridement: it permits contemporary cutting and removing of tissue with water, thanks to the high-pressure opening used by the device. Versajet (Fig. 38.3) seems to cause less damage to vital tissues compared to conventional surgical debridement and seems to be equally or more effective. In addition, it reduces surgical

time and hospitalization. Studies conducted on wound biofilms in a polymicrobial porcine model show how this tool is able to reduce inflammatory neutrophil markers and bacterial colonies about 1000 times [14, 15]. Finally, low-frequency and low-dose ultrasounds are able to break down dead tissue. These methods are all useful, painless, and capable of reducing the bacterial load, but they require several treatments [16, 17].

38.5 Aim of the Debridement Debridement accelerates the healing process. Necrotic tissue impedes the recovery of the wounds because of high bacterial counts. High bacterial load wounds are an obstacle to healing [18]. After the removal of the dead tissue, the wound can granulate and then epithelialize. The body is able to eliminate the necrotic tissue by itself, but it takes much longer [10]. Open skin wounds are all colonized by bacteria and if the bacterial load is >105 bacteria/g of tissue, healing is hindered. With quantitative cultures, it is possible to estimate the bacterial load of a wound [19]. With wide debridement we can eliminate the tissue most colonized by bacteria,

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and this reduces the necessity to perform quantitative cultures. An important obstacle to wound healing is tissue infection. Usually, infected tissues show some inflammation signs such as induration, warmth, pain with motion, erythema, and tenderness. However, these signs can be reduced or absent in immunocompromised patients and those who take corticosteroids. Another advantage of debridement is that it offers the possibility to take a piece of deep tissue that can be used for cultures and to determine its sensitivity to antibiotics. This is the best way to find the bacteria responsible for the infection: from the deepest area of the debridement or from the pus. In fact, the dry surface swab is not very reliable, usually, it results in skin contaminants; indeed, the correlation between the cultured bacteria of a surface swab and the bacteria responsible for cellulitis is really low [10]. With debridement, it is also possible to reduce the odor of an infected wound, evacuate the pus, and drain unroofed pockets. Another important advantage of debridement is that it helps to identify osteomyelitis that may be suspected during the physical examination with a positive probe to the bone [20]. Indeed, osteomyelitis is present in 85% of cases when a sterile cotton-tipped applicator is able to touch the bone; in the other 15% of cases, a layer of normal tissue usually overlies the bone and it is better not to remove it. In the operating room, during a general examination, the infected bone can be easily recognized: it usually does not bleed when biopsied and it is softer than the normal bone. When debriding bone, it is important to reach the solid and bleeding bone. A significant proof of the importance and the benefit derived from surgical debridement comes from the study of Steed et  al. [21] about a randomized blinded trial of PDGF (Regranex; Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) in the treatment of diabetic neurotrophic foot ulcers. In this study five centers enrolled more than ten patients and five centers enrolled less than or equal to ten patients each. The patients of these last five centers were put together to facili-

tate the analysis of the data. Patients of both groups received the same good wound care and the same saline-moistened gauze with or without PDGF. Before entering into the trial, every patient received a wide debridement and all the granulation and necrotic tissues and the calluses were removed. Likewise, during the ulterior follow-up visits, these tissues were removed. From this study it was noticeable that in both, the PDGF-treated group and in the control group, there was a direct relation between the incidence of debridement and healing rate: the more the wounds were debrided, the better they healed. It is important to stress that in every center, the group with PDGF showed a healing rate that was about twice higher compared to the control group. This means that clearly, PDGF helps in the process of wound healing independent of the level of care. Anyway, when PDGF was used in the context of wound care, the best healing rates were achieved. To start from a similar starting point at the beginning of the trial, before entering the study, patients with chronic wounds were treated with complete excision. This could have affected the excellent healing rates but, on the other hand, without this step, comparisons between patients may not have been possible. Another limitation of the study was the difference in the age of the wound which could have led to a different healing rate causing a bias in the system.

38.6 Wounds to Debride All patients with necrotic tissue present in their wounds or/and with pus draining from the wound are eligible for debridement. Also, pale granulation tissue should be debrided. Some evidence shows how senescent fibroblasts of chronic wounds are less capable of producing proteins and of replication. In fact, removing granulation tissue from a chronic wound permits the repopulation of young fibroblasts that are capable to control and improve the healing process better than the senescent ones; in addition, it also gives a normal aspect to the wound.

38  Surgical Debridement in Wound Care

Another tissue that should be removed is the callus at the margins of the wound: in this tissue, the blood supply is poor and it does not help the healing process, especially in areas like the plantar surface of the foot. In this area, where bony prominence is poorly padded with muscle, the perfusion of the skin comes from the rich collateral network of vessels within the skin itself. Whereas, in other tissues, skin perfusion usually comes from small vessels that arise from the muscle bed under the skin and that perforate the myofascia to perfuse the skin directly. In the foot, the callus that surrounds the wound can compress these vessels when pressure is applied to the plantar surface. For this reason, removing the callus can improve the perfusion of the wound. Debridement needs a specific method at a specific time. Ischemic wounds may require debridement, but ischemic tissue usually desiccates after debridement. Once debridement is carried on for normal tissue, the tissue dries and dies. In patients who need a revascularization procedure, it is better to perform a new blood supply into the wound as the first step and only later the debridement can be conducted, even days or weeks later. For instance, it may be necessary to perform a limited debridement with the drainage of the pus at first, followed by a bypass surgery, and finally a more extensive debridement once the new blood supply has been established. When a wound is covered by a dry and black eschar, usually this needs to be removed. Anyway, sometimes, thanks to this eschar, the wound below is kept humid and it also works as an antibacterial barrier, in addition, if the wound heals, the eschar will fall off. Here, we can see some cases when the eschar does not need to be excised [10]: • if there is no drainage from the wound, • if the patient is afebrile, • if the tissue all around the wound is not tender, • if it is firmly adherent, • if there is no inflammation around the wound.


38.6.1 Contraindications We can also identify some contraindications to wound debridement. This can be in the case of dry and intact eschars without clinical evidence of an infection below, this often happens in the unstageable pressure ulcer (grade 0) with undamaged eschar of the heel, sacrum, or buttock [22]. Other examples of wounds where debridement should be avoided are pathergy and wounds with pyoderma gangrenosum. In these cases, debridement worsens the wound unless there is undrained pus.

38.6.2 Debridement in Diabetic Foot [22] Sharp debridement can be considered a key point of wound control in patients with neuropathic and neuro-ischemic ulcers. In fact, this can probably be considered the best way to remove the associated biofilm that contains many species of bacteria and that forms communities of polymicrobial species. An example of surgical debridement in a diabetic foot is shown in Fig. 38.4. We are going to see these mechanisms in detail: Neuropathic Ulcer As we stressed above, debridement is the most important component of wound control. It is able to remove all the dead and senescent cells that cover the wound bed. Debridement is also very useful in ulcers because it supports and accelerates the process of wound healing, especially if it is practised regularly at every visit. The steps requieredfor this procedure are the following: • The removal of all calluses that surround the ulcer by a sterile scalpel. • All the necrotic tissue and the slough should be cut away. With a pair of forceps, it is possible to grip the material that needs to be removed, then gentle traction should be applied (if too much strength, the tissue can be torn and some dead material may remain on


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Fig. 38.4  Example of surgical debridement in diabetic foot

the surface) in order to keep the material under tension and to facilitate the cutting. Without this passage and only with the use of a scalpel blade, it is practically impossible to remove the moist slough. Forceps can also be used to probe an ulcer, in this way we can better estimate the true dimensions and depth of the ulcer itself. In addition, with dry gauze directly applied on the moist slough, it is possible to remove the moisture and so to facilitate the grip of the material to be removed. • Probe ulcer: if the probe reaches the bone there could be osteomyelitis. • It is important to send for culture a deep swab and tissue samples taken from the ulcer, but not from the surface callus because it is not very significant. • Ulcer should be cleaned with normal sterile saline or with an antiseptic such as Prontosan.

• Sterile dressing should be applied and held in place with a light bandage, a tubular one can be useful but it should not be too tight. • The patient should be reviewed every week, and every time these steps need to be repeated in order to maintain a correct debridement of the ulcer. Of course, if there are some problems before the planned control, the patient should return immediately for a visit. Neuroischemic Ulcer For neuroischemic ulcer, the procedures to follow are • First, evaluation needs to be done about the vascular status of the limb, which should be estimated with the ABPI score, only after that we can eventually proceed with debridement. In fact, if the foot is very ischemic, with an

38  Surgical Debridement in Wound Care

ABPI inferior to 0.5, only very cautious and gentle debridement should be performed. • Sometimes, ischemic ulcers develop a halo of thin glassy callus, this one can dry out and then become hard and curl up. In such cases, it can be useful to smooth off these areas because they can eventually catch on dressing and cause trauma to the tissue below. • Some precautions should be taken in patients with a very sensitive foot: it can be useful to anchor with forceps the tissue to debride while it is cut away. In this way, the painful dragging of the scalpel blade through the slack tissues can be avoided. • If in front of a thickened toenail we suspect a subungual ulcer, the nail should be cut off very gently or, alternatively, only some layers of the nail can be cut with a scalpel so that it is possible to expose and drain the ulcer below. Infected Neuropathic Ulcer Considering the neuropathic foot, the most changelling condition is the diabetic foot. Diabetic foot infections are very complicated. In fact, they often are more extensive than they seem at the beginning, from an initial examination and from the appearance of the surface. The best thing to do in this case is to perform an initial debridement in a clinical setting in order to understand the real dimensions of the lesion and to obtain a good tissue sample that can be analyzed for culture. Frequently, in the diabetic foot, over the ulcer we can find some calluses; only by removing these calluses we can reveal the real extension of the ulcer below, and then we can drain the pus and remove the infected sloughy tissue. With intravenous antibiotics, this kind of infection should heal, but it is necessary to follow the patients every day to detect the evidence of spread. Another useful trick is to draw on the foot an outline of the cellulitis area so that any variation (both extension or reduction) can be easily and quickly detected. If the infection is severe, in addition to the ulcer we can also find extensive infected sloughing subcutaneous tissues, including tendon and fascia. In this case, the tissue starts to break down and liquefy, but it does not result in frankly


necrotic tissue. For correct treatment of this kind of lesion, this tissue should be removed with an operation. Here are the indications for urgent surgical operation in patients with infected neuropathic ulcers: • Large area of infected sloughy tissue. • The presence of pus and some localized fluctuance. • X-ray that shows the presence of crepitus gas in the soft tissue. We also have to consider that the air in an ulcer can mean the presence of gas in the deep tissue of the foot or leg, which is the worst option, but it also can mean that some air has entered into the foot through the ulcer, that is a less bad option. • Purplish discoloration of the skin that usually stands for subcutaneous necrosis. • Osteomyelitis that does not respond to conservative measures of therapy. • The development of fluid collections of pus that are improbable to detect clinically. MRI has an important role in the identification of the last two indications of surgery. Indeed, it can help both in detecting fluid collection and identifying the presence of osteomyelitis. The contrast agent that is used, gadolinium, is injected intravenously and it tends to concentrate in the area of inflammation, in this way MRI is useful in increasing the sensitivity of the diagnosis of these clinical features. Nevertheless, we also have to remember that MRI can show some false-­positive diagnoses, so it has some limitations. Infected Ischemic Ulcer A procedure of surgical debridement can also be necessary for severely infected wounds. In this case, when we have to decide to operate a patient, we tend to use criteria that are very similar to those used for the neuropathic foot. Of course, considering that these patients have an ischemic substrate, surgical debridement also needs a study of the arterial perfusion of the foot in order to estimate the potential of the surgical wound to heal. For this reason, all these patients need urgent vascular investigation before a surgical plan.

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436 Additional Surgery Sometimes debridement can be insufficient and other procedures such as digital or ray amputation is necessary to establish a drainage. The techniques that can be performed are the following: • For apical infection or apical osteomyelitis, a partial digital amputation can be performed. In the case of the infected toe, the wound can be left temporarily open and the closure can be delayed. Alternatively, the toe can be disarticulated at the interphalangeal joint and a skin flap of the plantar and the dorsal part of the foot can be considered. • According to the Faraboeuf procedure, the amputation of the hallux may also include the removal of the metatarsal head and part of the shaft in order to facilitate the closure and to reduce as much as possible future ulceration of the skin. • On the other hand, for the lesser toes the amputation should be performed through the metatarso-phalangeal joints. • If there is an infection of the toe that spreads only to the forefoot, a ray amputation should be performed that includes the removal of the toe and part or all of its corresponding metatarsal. • In case of extensive forefoot infection, the amputation performed can be an open transmetatarsal one or a Lisfranc and Chopart’s partial foot amputation.

38.7 Larvatherapy In particular cases such as neuroischemic foot, in order to debride ulcers we can also use the larvae of the green bottle fly (Lucilia sericata). With the larvae, it is possible to achieve an atraumatic physical removal of the necrotic material. In addition, they are also able to produce secretions rich in antimicrobial activity against Gram-­ positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA).

Furthermore, from a medical maggot farm, sterile maggots can be obtained that can be used for these purposes [22]. Take Home Messages

• Debridement consists of the removal of the necrotic area, dead tissues, and eventually the drainage of wound pockets with pus. • It can be radical or conservative, the choice is related to the ability to distinguish vital and nonvital tissues. • Debridement is not only a procedure of wound cleaning but it is a fundamental step in the wound healing process. • Removing necrotic tissue helps to reduce bacterial load and the risk of infection. • It is important to pay attention when it is executed in patients with ischemic problems.

References 1. Sibbald R, Williamson D, Orsted H, Campbell K, Keast D, Krasner D, Sibbald D. Preparing the wound bed—debridement, bacterial balance and moisture balance. Ostomy Wound Manage. 2000;46:9. 2. Schultz G, Sibbald R, Falanga V, Ayello E, Dowsett C, Harding K, Romanelli M, Stacey M, Teot L, Vanscheidt W.  Wound bed preparation: a systematic approach to wound management. Wound Repair Regen. 2003;11:S1. 3. Chin G, Schultz G, Stacey M. Principles of wound bed preparation and their application to the treatment of chronic wounds. Primary Intention. 2004;11:171–4. 4. Sibbald R, Orsted HL, Coutts PM, Keast DH.  Best practice recommendations for preparing the wound bed: update 2006. Adv Skin Wound Care. 2007;20:406. 5. Vowden KR, Vowden P.  Wound debridement, Part 1: Non-sharp techniques. J Wound Care. 1999;8(5):237–40. 6. Fowler E, van Rijswijk L. Using wound debridement to help achieve the goals of care. Ostomy Wound Mange. 1995;41(7A Suppl):23s–35s. 7. Milward PA.  Common problems associated with necrotic and sloughy wounds. Br J Nurs. 1995;4(15):896–900.

38  Surgical Debridement in Wound Care 8. Smith F, Dryburgh N, Donaldson J, Mitchell M.  Debridement for surgical wounds. Cochrane Database Syst Rev. 2011;11, no. 5:CD006214. 9. Vowden KR, Vowden P. Wound debridement, Part 2: Sharp techniques. J Wound Care. 1999;8(6):291–4. 10. Steed DL.  Debridement. Am J Surg. 2004;187(5A):71S–4S. 11. Sculley RE, Artz CP, Sako V. An evaluation of the surgeon criteria for determining viability of muscle during debridement. Arch Surg. 1956;73:1031–5. 12. Klein MB, Hunter S, Heimbach DM, Engrav LH, Honari S, Gallery E, Kiriluk D, Gibran NS.  The Versajet water dissector: a new tool for tangential excision. J Burn Care Rehalbil. 2005;26(6):483–7. 13. Pascone M, Papa G, Ranieri A. Use of a novel hydrosurgery device in surgical debridement of difficult-to-­ heal wounds. Wounds. 2008;20(5):139–46. 14. Allan N, Olson M, Nagel D, Martin R.  The impact of Versajet hydrosurgery debridement on wounds containing bacterial biofilms. Wound Rep Regen. 2010;18:A88. 15. Sainsbury DC.  Evaluation of the quality and cost-­ efectiveness of Versajet hydrosurgery. Int Wound J. 2009;6(1):24–9.

437 16. Gray D, Stang D. Ultrasound-assisted wound debridement. Wounds. 2010;6(4):152–62. 17. Strohal R, Dissemond J, O'Brien JJ, Piaggesi A, Rimdeika R, Young T, Apelqvist J. EWMA document: debridement. An updated overview and clarification of the principle role of debridement. J Wound Care. 2013;22(1):S1. 18. Robson MC, Stenberg BD, Heggers JP. Wound healing alterations caused by infection. Clin Plast Surg. 1990;17(3):485–2. 19. Robson MC.  Wound infection. A failure of wound healing caused by an imbalance of bacteria. Surg Clin North Am. 1997;77(3):637–50. 20. Grayson ML, Gibbons GW, Balogh K, Levin E, Karchmer AW.  Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis in diabetic patients. JAMA. 1995;273(9):721–3. 21. Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic ulcer study group. J Am Coll Surg. 1996;183(1):61–4. 22. Edmonds ME, Foster AVM. Managing the diabetic foot, 3rd edition. Wiley Blackwell.

Reconstructive Options in Wound Care: From Simplest to Most Complex


Marco Pappalardo, Francesca Lolli, Melba Lattanzi, and Giorgio De Santis

39.1 Introduction Management of chronic ulcers is one of the major challenges to healthcare systems worldwide. In the United States alone chronic ulcers affect around 2.4–4.5 million people [1, 2]. It is mainly a condition of the elderly, and it is associated with high treatment costs due to the difficulty in treating [3, 4]. In the United States, around $26.8 billion is the total annual cost of chronic injuries [1, 5]. In the UK, a range from £1.4 to 2.1 billion per annum represents the estimated cost for pressure injuries to the NHS [6]. Chronic ulcers can be categorized as venous or arterial vascular ulcers, diabetic ulcers, and pressure ulcers [7]. These conditions present similar features, including prolonged inflammation, infections, the presence of drug-resistant microbial biofilms producing hypoxia, ischemia, and necrosis. Pressure ulcers are linked with particular positions giving protracted pressure on the skin and underlying soft tissue, such as sacral pressure ulcers in the supine position and ischial pressure M. Pappalardo (*) · F. Lolli · M. Lattanzi · G. De Santis Division of Plastic and Reconstructive Surgery, Department of Medical and Surgical Sciences, Policlinico University Hospital, University of Modena and Reggio Emilia, Modena, Italy e-mail: [email protected]; giorgio. [email protected]

ulcers in the sitting position, occurring most frequently in patients with long-term immobilization [8]. Indeed, during the COVID-19 pandemic, patients presenting severe acute respiratory distress syndrome (ARDS) requiring prone positioning to maximize mechanical ventilation frequently suffered pressure sores in atypical locations such as forehead, chin, shoulders, chest, iliac crest, pelvis, genitalia, knees, dorsal feet, and toes [9, 10]. Increased awareness, improved preventive measures, and earlier diagnosis and intervention remain the mainstay in the management of chronic pressure ulcers. Then, reducing further progression and deterioration of ulcers are, indeed, important. For grade I and II pressure sores, conservative treatment is suggested aiming to remove and address any influencing risk factor. In patients with grade II or above pressure ulcers, debridement of devitalized tissue from the wound bed is necessary to promote wound healing. Wound care includes several tools, including growth factors, extracellular matrices, engineered skin, and negative pressure wound therapy (NPWT) [4]. Reconstructive surgical procedures may be indicated in grade III–IV pressure ulcers. Many reconstructive surgery options are available for the treatment of such ulcers, from simple interventions such as direct closure and skin grafting with or without skin substitutes to more complex procedures such as soft tissue flap reconstruction.

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,



No clear guidelines are reported regarding one particular soft tissue flap for the reconstruction of pressure sores at different stages. This chapter provides a brief overview of the treatment of chronic and pressure ulcers and soft tissue injury in several anatomical locations, with particular emphasis on proper reconstructive surgical procedures.

39.2 Management of Chronic and Pressure Ulcers A multidisciplinary approach is crucial for the appropriate treatment of patients with chronic wounds, including clinicians, infectious disease doctors, plastic surgeons, orthopedic surgeons, anesthetists, physiotherapists, nutritionists, tissue viability nurses, and social workers [11, 12]. The goals of treatment for patients with chronic pressure wounds are preventing complications, especially infection; preventing the wound from increasing in size; and preventing the injuries from going to other locations, and closure of the wound [13]. However, the surgical closure of chronic pressure injuries is often complicated by high recurrence rates reported in the literature. Before considering a patient a potential candidate for surgery, several considerations need to be taken into account. Assessment of the patient is fundamental, including his overall health and physical, nutritional, social, psychological status, and education. Then, assessment proceeds with ulcer evaluation, wound care, management of infection, and surgical procedures in selected patients [14]. Preoperative imaging modalities such as computed tomography and magnetic resonance during preoperative workup can be helpful for the diagnosis of osteomyelitis; however, bone biopsy and culture are required to confirm the diagnosis. Experienced doctors should consider the patient’s social status and his compliance when deciding the appropriate treatment for a chronic pressure injury [15]. Factors that predispose patients to pressure-induced injuries are sometimes the same factors associated with recurrence

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after surgical reconstruction; hence, patient selection and preoperative preparation are crucial. The clinical stage is fundamental for the individualized management of pressure ulcers and soft tissue injuries. The most adopted staging system is the National Pressure Sore Advisory Panel Consensus Development Conference 2007 [16]. Stage I and II injuries are generally treated conservatively with proper wound care and the removal of factors causing the initial injury. Treatment of stage III and IV ulcers often requires surgical management to achieve wound closure, significantly improving the quality-of-life of these patients [17, 18].

39.3 Conservative Treatment and Wound Care For all patients with chronic ulcers, the principles of wound care should be applied. Surgical debridement of devitalized tissues and dressing care to provide control of the wound are paramount in wound care [19]. Grade II chronic pressure ulcers showing a necrotic or shedding wound can be treated with debridement at the bedside to increase the wound healing and, indeed, precisely stage the ulcer. The necrotic eschar is surgically debrided, and healing is achieved by secondary intention from the periphery. For extensive grade III or IV chronic pressure ulcers, proper surgical debridement in the operating room is safer and more effective due to pain and discomfort of the patients, risk of bleeding, and not adequacy of debridement. Indeed, accurate hemostasis is imperative due to the high propensity of these wounds. There is a plethora of available dressings, growth factors, and adjunctive therapies without evidence that any type of wound care protocol is superior [19]. Appropriate wound care using dressings are able to keep a clean moist environment and maintaining the surrounding skin dry. Indeed, patients with poor clinical conditions or where extensive soft tissue reconstruction is

39  Reconstructive Options in Wound Care: From Simplest to Most Complex

not possible are generally treated with in-bed debridement and conservative management of the wounds. In such instances, minimal-serial debridement with secondary-intention healing is attempted, and it is considered an acceptable option. However, this method can impact the cosmetic result leaving scarring areas. Alternative therapies, such as negative pressure wound therapy (NPWT) may be considered for certain types of ulcers. This tool offers controlled, continuous-intermittent sub-atmospheric pressure over an open wound, improving the local wound environment, and speeding healing and wound closure. NPWT is able to facilitate the production of granulation tissue and gradual healing of less complex defects. Recently, NPWT has been used for the temporization of traumatic wounds, as well as the management of chronic wounds [20, 21]. NPWT is able to approximate skin flaps, increase tissue perfusion, decrease the dead space, and favor marginal apposition of the wound edge, improving wound healing, especially in patients treated with direct closure or skin graft. Hence, this method is very useful for older patients not able to tolerate surgical treatment, as well as for patients with a paucity of local reconstructive options [22]. NPWT can also deliver instillation of antiseptics to the wound bed. It has been reported that approximately 75% of grade II pressure ulcers heal with proper conservative treatment [23]. We generally prefer to treat grade II pressure ulcers using paraffin gauze together with hyaluronic acid and collagenase ointment monitoring the healing process. In patients with infection and a large amount of fibrin, we prefer chemical debridement with chloramphenicol and collagenase. Instead, grade III and IV chronic pressure ulcers more frequently require surgical treatment [24].

39.4 Surgical Indications Indications for the surgical management of chronic wounds include substantial necrosis, osteomyelitis, wounds producing systemic infec-


tion, sepsis, or bacteriemia, as well as the deterioration of patient’s functional status [25].

39.5 Surgical Debridement The aim of surgical debridement is to achieve a viable wound bed removing all potentially contaminated and devitalized tissues as initial management. In the wound-healing process, debridement should be performed aggressively, also referred to as radical wound debridement [26]. Osteotomy of bony prominences should also be performed to leave a smooth surface and decrease local pressure. During debridement, microbiological swabs and tissue biopsy should be taken to rule out any bacterial growth. Patients with deep pressure ulcers involving the bone need bone biopsies to exclude osteomyelitis [27]. Following initial debridement, definitive reconstruction of the defect is performed at the same stage or later in a second-stage, depending on the amount of necrotic tissue, the ability to perform proper debridement, the nutritional status of the patient, general condition, and the surgeon’s decision. In the literature, there are advocates for both approaches to pressure ulcer reconstruction: single-stage (debridement plus reconstructive surgery) and multiple-stage; however, no randomized trials have been reported comparing the two methods regarding complications and recurrence rates [28]. Delayed reconstruction is generally preferred in infected wounds to achieve microbiological diagnosis and proper antibiotic treatment. Single-­ stage procedure may be performed in case a wound is not grossly contaminated [29]. We generally prefer a multiple-stage approach to achieve a meticulous debridement, an appropriate antibiotic therapy due to the availability of swabs culture for the reconstructive stage of the procedure. Indeed, multiple wound debridements may be necessary in some cases to achieve adequate wound bed, remove necrotic tissue, and control infection before planning a definitive surgical reconstruction.

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39.6 Reconstruction Methods

39.6.3 Flaps

Following thorough debridement and wound bed preparation, several reconstruction options can be chosen depending on the defect. Plastic and reconstructive surgeons used to follow the “reconstructive ladder” to manage complex defects. The aims of reconstructive procedures are to achieve adequate wound coverage, offer proper soft tissue padding to protect the area from the pressure forces, prevent recurrence, and increase wound closure and healing, with minimal donor-site morbidity [30].

Several flap options have been introduced for chronic ulcer reconstruction depending on the defect type and size. Many types of musculocutaneous, fasciocutaneous, and perforator-based flaps have been reported in ulcer surgery [34]. Using a well-vascularized local or a free soft tissue flap with adequate padding in the pressure points and tension-free closure [35], the reconstructive surgeon can provide better form and functional results. Indeed, additional tools such as tissue expansion and NPWT can provide further help in the reconstruction of ulcer defects [36]. Locoregional flaps, including skin, fascia, or muscle, are the most common techniques used for this purpose. Historically, musculocutaneous flaps were favored due to their reliability, good vascularity, and their bulk with the ability to fill large deep defects. More recently, fasciocutaneus and perforator flaps also gained popularity for the reconstruction of ulcer defects [37]. However, muscle flaps have a low tolerance for ischemia. On the other hand, fasciocutaneous flaps present several advantages including less sensitivity to ischemic injury, higher mechanical resistance to pressure forces, less functional morbidity in mobile patients, and with preservation of muscle flaps for recurrences [38, 39]. Fasciocutaneous flaps have been used for the reconstruction of grade III and IV pressure injuries. Recently, fasciocutaneous and perforator flaps have been performed in patients with underlying osteomyelitis, with a flap survival of 95.8% [40]. A systematic review comparing musculocutaneous, fasciocutaneous, and perforator flaps did not find any significant difference regarding complication rates or recurrences between the flap types [34]. Chronic ulcers needing microsurgical reconstruction are those that cannot be closed by local flaps or skin grafts, complex wounds with exposed tendons and bones, or wounds with prolonged infections, skin necrosis, and osteomyelitis [41]. Hence, when a chronic wound is stalling, complex, and challenging to treat with local tissues, microsurgical reconstruction together with

39.6.1 Primary Closure Primary closure is the simplest method and depends on the availability of skin following the debridement of the wound. In pressure ulcers, this method is rarely possible due to the amount of underlying soft tissue injury [25]. Since pressure-induced injuries are frequently large, direct excision and primary closure of them can produce wound dehiscence, especially when the patient moves due to the tension across the wound edge. Indeed, a high recurrence rate has been reported after the direct closure of chronic pressure ulcers [31]. Hence, primary closure is only suggested in small non-contaminated and superficial ulcers.

39.6.2 Skin Grafting Skin grafts may be used only in small and superficial chronic wounds. Skin grafts require an accurate wound bed preparation, and it is performed only in wounds without exposure of vital structures such as the bone or tendons [32]. A skin graft after granulation over an exposed bone can still achieve skin coverage but it can lead to complications, including further soft-tissue defects, unstable wounds, osteomyelitis, functional loss, and increased costs. It is a suboptimal reconstructive treatment for pressure injuries due to the inability to provide enough bulk to bony prominences, often leading to recurrence [33].

39  Reconstructive Options in Wound Care: From Simplest to Most Complex

a multidisciplinary team can provide adequate and timely reconstruction. Free flaps such as latissimus dorsi (LD), anterolateral thigh, and tensor fascia lata flaps, among others, have been reported for the reconstruction of chronic pressure ulcer defects. Free latissimus dorsi (LD) flap is generally not performed in paraplegic patients, as they rely on upper-body strength for mobilization. Using a


partial split latissimus dorsi flap is an adequate option to preserve muscle function if the defect is not too large [42]. Flap selection clearly is different according to the ulcer location (Table  39.1). Most pressure ulcers are located in the sacral and ischial regions in the back part of the body. Hence, reconstruction of these regions requires a prone position except for the trochanteric region.

Table 39.1  Reconstructive modalities of pressure ulcers in various anatomical locations Ulcer Location Sacral

Cause Prolonged position without proper pressure relief or mobilization


Prolonged sitting without proper pressure relief or cushion


Direct pressure from a prominent greater trochanter in insensate and sensate patients


Pressure in the posterior aspect of the heel in immobile or bedridden patients

Elbow (Olecranon)

Continuous mechanical shearing and pressure forces in the periolecranon region

Reconstructive procedure following surgical debridement Flap Reconstruction with: • Gluteus Maximus Myocutaneous Flap (rotation, V–Y advancement, sliding island, splitting • Superior Gluteal Artery Perforator (SGAP) Flap • Inferior gluteal artery perforator (IGAP) flap Flap Reconstruction with: • Gluteus Maximus Myocutaneous Rotation Flap (rotation, split) • V-Y Hamstring Muscle Advancement Flap • Tensor Fasciae Latae Musculocutaneous Flap • Combined Gracilis Muscle Flap for Ischial coverage and Medial Thigh Rotation Fasciocutaneous Flap • Rectus Abdominis Flap • Gluteal Fasciocutaneous Flap (rotation) • Medial thigh Fasciocutaneous Flap • Posterior thigh Fasciocutaneous Flap V-Y • IGAP flap Flap Reconstruction with: • Tensor Fasciae Latae (TFL) Flap (V-Y advancement, rotation, transposition, islanded, perforator) • Anterior Lateral Thigh Flap and Vastus Lateralis Flap • Distal Gluteus Maximus Myocutaneous Rotation Flap • Rectus Femoris Muscle Flap Skin grafts Flap Reconstruction with: • Medial Plantar Flap • Reverse Sural Flap • Perforator-­Propeller flaps • Free Gracilis Flap • Free Radial Forearm Flap • Free Anterior Lateral Thigh Flap Flap Reconstruction with: • Lateral Arm Fasciocutaneous Flap • Radial Forearm Flap • Oblique External Fasciocutaneous Flap • Anconeus Muscle Flap • Brachioradialis Musculocutaneous Flap • Flexor Carpi Ulnaris Muscle Flap • Extensor Carpi Radialis Longus Musculocutaneous Flap • Perforator Flaps (from the dorsal aspect of the upper forearm) (continued)

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444 Table 39.1 (continued) Ulcer Location Posterior Scalp (Occiput)


Cause Direct pressure from special head stabilization equipment in patients with prolonged immobilization requiring mechanical ventilation Prone positioning to maximize mechanical ventilation in COVID-19 patients

Reconstructive procedure following surgical debridement Secondary treatment of alopecia with tissue expansion and local flaps Skin grafts Flap Reconstruction with: • Scalp Flaps (transposition or rotation) Local Flaps Secondary autologous fat grafting to reduce the patient’s pain, improve chin contour and scar contracture

39.7 Reconstructive Procedures by Site 39.7.1 Sacral Ulcers Local flaps, such as musculocutaneous and fasciocutaneous, can be used for the reconstruction of sacral defects. Flaps can be designed as advancement, rotation, or in islanded fashion. They can be unilateral or bilateral, depending on the size of the defect. Musculocutaneous and muscle flaps are preferred for large-deep sacral defects in thin patients for whom fasciocutaneous flaps may not be adequate to provide wound coverage and padding. Gluteus maximus musculocutaneous flap based on one or both the superior gluteal or inferior gluteal vessels is the main flap used for sacral coccygeal defects. It can be designed as a rotation [43], V-Y advancement [44, 45], or transverse-­ splitting partial gluteal flaps [46]. The flap choice depends on the ulcer size and if it is primary or recurrent ulcer. A primary ulcer can be closed with a simple flap, whereas a recurrent ulcer requires a large-complex flap. In ambulatory patients, it is not suggested to totally detach the gluteus maximus inferiorly to prevent a functional deficit, using the muscle only after exhausting other surgical options. Fasciocutaneous options include the superior gluteal artery perforator (SGAP) flap and inferior gluteal artery perforator (IGAP) flap, [47, 48] and are useful especially in ambulatory patients. They can be designed as V-Y advancement, rotation, Limberg, hatchet, transverse lumbar, or combinations of flaps. The SGAP flap was first

described in 1993 by Koshima et  al. for the reconstruction of a sacral pressure defect [49]. This perforator flap shows good vascularity and is generally performed as an alternative choice for microsurgical breast reconstruction [50]. It has also been described for sacral and lumbar reconstruction [51, 52]. Overlapping tissue layers by partially de-epithelializing and burying the V-Y advancement flap are commonly performed to avoid a single weak suture line between the skin and areas of bony debridement with long-­ term durability. However, these areas can require longer healing time and further surgery in the case of complications.

39.7.2 Ischial Ulcers Ischial pressure ulcers are the most frequent ulcers in paraplegic patients on the pelvis, presenting a high incidence of recurrence [53]. The main cause of this injury is prolonged sitting without proper pressure relief or cushion. Ischial pressure sores often show small skin defects with a large-penetrating cavity underneath. There are various types of flaps available to reconstruct an ischial pressure ulcer. Reconstruction of ischial defects should be planned considering that the patient needs hip flexion to facilitate sitting. Fasciocutaneous flaps include gluteal rotation, medial thigh, posterior thigh V-Y, hatchet advancement flaps, and IGAP flaps [54, 55]. Musculocutaneous options described most commonly include inferior gluteus maximus musculocutaneous rotation flap based on inferior gluteal perforators vessels [56], V-Y hamstring muscle

39  Reconstructive Options in Wound Care: From Simplest to Most Complex





Fig. 39.1 A 58-year-old paraplegic woman with an ischial pressure sore measuring 13 × 9 cm2 after failure of a 5-month conservative treatment (a). Patient underwent surgical debridement followed by dual-plane closure of the defect combining a pedicled gracilis muscle flap with

a V-Y fasciocutaneous thigh flap vascularized by two perforator vessels coming from the profunda femoris artery, assessed preoperatively by Doppler-US (b). Intraoperative view at the end of the surgical intervention (c)

advancement flap [57], transversely split gluteus maximus advancement, TFL musculocutaneous, gracilis muscle based on medial femoral circumflex artery [58], biceps femoris advancement/folding based both on profunda femoris perforators, and rectus abdominis flaps (Fig. 39.1) [59].

39.7.3 Trochanteric Ulcers Trochanteric pressure ulcers, although less frequent, often are higher-grade pressure ulcers due to the mobility and direct pressure of the greater trochanter and a large amount of soft tissue


undermined. Skin ulceration is often accompanied by the extension into the trochanteric bursa. Musculocutaneous flaps are generally preferred over fasciocutaneous flaps due to the significant bony prominence of the trochanter regions as well the paucity of the fasciocutaneous tissue available with adequate thickness providing durable padding. The most commonly performed musculocutaneous flap for trochanteric defect coverage is the tensor fasciae latae (TFL) flap based on the lateral femoral circumflex artery. The TFL flap presents several advantages, such as predictable and reliable blood supply, minimal donor-site morbidity, and minimal effect on lower extremity motor strength. TFL can be harvested as a V-Y advancement flap, as a rotation flap, transposition flap, or islanded in a perforator fashion [60]. Indeed, anterior lateral thigh, vastus lateralis, distal gluteus maximus myocutaneous rotation flap, and rectus femoris muscle flaps are also used for trochanteric defect coverage [60].

39.7.4 Heel Ulcers The posterior heel is particularly predisposed to the development of pressure injuries in bed-­ bound patients. The posterior aspect of the heel has thinner skin and small fat overlying; hence, defects at this level with tendon and/or bone exposure represent a challenge for surgeons due to the lack of local tissue available. Traditionally, upper-middle third of the lower leg can be managed with locoregional muscle flaps such as gastrocnemius and soleus muscles or with local perforator-propeller skin flaps. However, in the lower third of the leg and in the foot, due to the scarcity of available local tissues, microsurgical reconstruction is warranted when the defect is moderate or large in size. Pressure ulcers in this region require a durable and well-­ vascularized soft tissue flap with adequate volume. Heel ulcers with stage I or II are commonly treated conservatively by pressure off-loading with specially designed boots and attentive wound care. Factors associated with the forma-

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tion of heel pressure ulcers are prolonged immobilization, diabetes mellitus, reduced perfusion (peripheral artery disease) of the lower extremity, and poor physiological condition [61, 62]. Wound healing may lead to wound dehiscence and rapid recurrence in poorly vascularized limbs. Hence, it is fundamental to check the limb vascularity when considering flap reconstruction of heel ulcers. Preoperative evaluation includes radiographic imaging to rule out osteomyelitis. A vascular mapping of lower limbs is highly suggested before attempting a microsurgical reconstruction to evaluate the patency of recipient vessel. The first surgical step for heel ulcers is debridement, also involving the calcaneal bone if necessary. Flap options for reconstruction of heel defects include locoregional flaps such as medial plantar artery [63], reverse sural artery [64], perforatorspropeller flaps, and rarely transposition flaps [65]. Microsurgical flap reconstruction is more needed for this region compared with other anatomic areas [66].

39.7.5 Elbow Olecranon Ulcers Elbow pressure ulcers may involve the olecranon or medial elbow bony prominences in patients with continuous mechanical shearing and pressure forces in the periolecranon region. Injuries in this area are often associated with chronic bursitis [67]. For small, simple injuries, conservative management with or without direct closure is performed. In case of more complex wounds, flap options include local rotation, transposition or island fasciocutaneous flaps [68], perforator flaps from dorsal aspect of upper forearm [86], radial forearm flap [69], or reverse lateral arm flap [70], and muscle flaps [71, 72].

39.7.6 Posterior Scalp (Occiput) Ulcers Posterior scalp pressure ulcers can be found in patients requiring mechanical ventilation in

39  Reconstructive Options in Wound Care: From Simplest to Most Complex

intensive care unit due to prolonged immobilization or head stabilization equipment, such as neck collars or intracranial pressure monitoring [73]. The management of these injuries is mostly conservative with wound care, and improvement usually depends on the patient’s clinical condition and removal of head equipment. A long-term sequela of posterior scalp pressure ulcers is alopecia [74]. Secondary treatment of alopecia includes excision and primary skin closure, or in case of large defect tissue expansion and local flaps may be used. In case of extensive, more complex scalp chronic pressure injuries following debridement and wound care, skin graft or local flaps are warranted. Deep pressure ulcers exposing the cranial bone or with concomitant osteomyelitis require extensive debridement and reconstruction with locoregional transposition or rotation scalp flaps.

39.7.7 Atypical Locations of Pressure Ulcers during COVID-19 Pandemic Due to the spread of the COVID-19 pandemic, many patients required intensive care treatment with prone therapy to maximize mechanical ventilation due to severe acute respiratory distress syndrome (ARDS) [75, 76]. Although prone positioning is recommended by critical care guidelines for patients with ARDS, COVID-19-­ related, long periods (>16  h per day) in this position may induce several complications [77]. The most frequent complication of this rescue treatment is pressure ulcers in highrisk and uncommon body areas [78]. Etiological factors of these pressure-induced injuries involve duration and quantity of pressure with the long-term exclusion of blood flow to tissues, friction and shearing forces on soft tissues, and bony prominences with tissue perfusion pressure for a long period of time. In patients requiring prone positioning, pressure ulcers can be found in forehead, chin, shoulders, chest, iliac crest, pelvis, genitalia, knees, dorsal feet, and


toes. Pressure-induced necrosis of the chin has rarely been described complication in routine practice [79]. Ibarra et al. reported that the total number of days in prone positioning for more than 24 h is the most important risk factor associated with pressure-induced injuries [80]. It is critical to roll the patient regularly to reduce pressure forces in high-risk areas and use proper pressure-redistribution surfaces. Recently, we have reported five COVID-19 patients treated in the ICU with prone mechanical ventilation who developed pressure ulcer necrosis of the chin [81]. The plastic surgery team treated these injuries with initial in-bed surgical debridement on an average of 1 week after the ulcers became necrotic, followed by conservative treatment. Complete healing was achieved in around 2.5 months, however, leaving an area of patchy alopecia and scar. Although local flaps can have advantages such as faster healing, better cosmetic result, and less number of medications needed, however, COVID-19 patients affected are very fragile and, hence, conservative management of the wounds was adopted. Secondary autologous fat grafting (AFG) [82, 83] was performed in patients with secondarily healed wounds in the chin as a revision procedure to reduce the patient’s pain, improve chin contour, and minimize cosmetic sequelae and scar contracture (Fig.  39.2). The average of fat grafting injected into the chin was 8 mL. All patients were satisfied based on scar appearance, chin contour-­ projection, and none of them complained pain. Hence, the Vancouver scale showed an improvement in chin scars. Autologous fat grafting has been largely used to reduce scar retraction and contracture and in therapeutic scar patch as well as in regenerative medicine [84–86]. It has been reported the possibility to increase wound healing by performing autologous fat grafting before wound closure as an adjuvant treatment to avoid scar contracture and reduce pain [87–89]. In our study we used secondary autologous fat grafting when patients conditions were settled in order to correct and improve the chin contour.

M. Pappalardo et al.





Fig. 39.2  A 68-year-old man with a 5  ×  3  cm necrotic pressure ulcer in the chin due to mechanical ventilation in the prone position for ARDS COVID-19 related (a). Initial surgical debridement of the necrotic eschar was performed followed by wound care using daily heliotherapy, hyaluronic acid/collagenasis ointment, and paraffin

gauze. Secondary-intention wound healing was achieved in around 2  months leaving an anesthetic scarring area (b). Secondary autologous fat grafting was performed 8 months later improving the chin contour and projection (c)

39  Reconstructive Options in Wound Care: From Simplest to Most Complex

39.8 Conclusions


7. Nunan R, Harding KG, Martin P. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity. Dis Model This chapter is to provide an overview of the variMech. 2014;7(11):1205–13. dmm.016782. ous reconstructive options available for the treat8. Hsu KF, Kao LT, Chu PY, et al. Simple and efficient ment of chronic pressure ulcers in common and pressure ulcer reconstruction via primary closure atypical anatomical locations. At present, no concombined with closed-incision negative pressure sensus has been established regarding the most wound therapy (CiNPWT)-experience of a single surgeon. J Pers Med. 2022;12(2):182. https://doi. appropriate reconstructive procedure for chronic org/10.3390/jpm12020182. pressure ulcers in particular locations. Several 9. Baccarani A, Pappalardo M, Starnoni M, De Santis factors can guide for the suitable reconstructive G. Plastic surgeons in the middle of the coronavirus option including the ulcer defect and grade, risk disease 2019 pandemic storm in Italy. Plast Reconstr Surg Glob Open. 2020;8(5):e2889. https://doi. factors, general condition of the patient, quality org/10.1097/GOX.0000000000002889. of the surrounding tissues, morbidity of the donor 10. Starnoni M, Baccarani A, Pappalardo M, De Santis site, surgeon preference and microsurgical expeG. Management of personal protective equipment in rience, and the patient’s expectations. The patient plastic surgery in the era of coronavirus disease. Plast Reconstr Surg Glob Open. 2020;8(5):e2879. https:// education and compliance in the preoperative and postoperative period are of paramount impor11. Lindqvist EK, Sommar P, Stenius M, Lagergren tance especially regarding the rehabilitation proJF.  Complications after pressure ulcer surgery  - a tocol and pressure preventive regimes.Financial study of 118 operations in spinal cord injured patients. J Plast Surg Hand Surg. 2020;54(3):145–50. https:// Disclosure StatementThe authors have nothing to disclose. No funding was received for this 12. Chiang IH, Wang CH, Tzeng YS.  Surgical treatarticle. ment and strategy in patients with multiple pressure sores. Int Wound J. 2018;15(6):900–8. https://doi. org/10.1111/iwj.12942. 13. Tchanque-Fossuo CN, Kuzon WM.  An evidence-­ References based approach to pressure sores. Plast Reconstr Surg. 2011;127(2):932–9. 1. Padula WV, Delarmente BA.  The national cost of PRS.0b013e3182046a02. hospital-acquired pressure injuries in the United 14. Anon. Pressure ulcers in adults: prediction and preStates. Int Wound J. 2019;16(3):634–40. https://doi. vention. Clinical practice guideline nAfHCP.  Panel org/10.1111/iwj.13071. for the Prediction and Prevention of Pressure Ulcers 2. Richmond NA, Maderal AD, Vivas AC.  Evidence-­ in Adults. Dermatol Nurs. 1992;5(1):17–33. based management of common chronic lower extrem15. Marriott R, Rubayi S.  Successful truncated osteoity ulcers. Dermatol Ther. 2013;26(3):187–96. https:// myelitis treatment for chronic osteomyelitis ary to pressure ulcers in spinal cord injury patients. 3. Rice JB, Desai U, Cummings AK, Birnbaum HG, Ann Plast Surg. 2008;61(4):425–9. https://doi. Skornicki M, Parsons NB.  Burden of diabetic foot org/10.1097/SAP.0b013e318162f257. ulcers for medicare and private insurers. Diabetes 16. Develop- NPSAPC, ment Conference Staging System Care. 2014;37(3):651–8. FA. Accessed 29 Nov dc13-­2176. 2009. 4. Shankaran V, Brooks M, Mostow E. Advanced thera17. Kruger EA, Pires M, Ngann Y, Sterling M, Rubayi pies for chronic wounds: NPWT, engineered skin, S. Comprehensive management of pressure ulcers in growth factors, extracellular matrices. Dermatol spinal cord injury: current concepts and future trends. Ther. 2013;26(3):215–21. J Spinal Cord Med. 2013;36(6):572–85. https://doi. dth.12050. org/10.1179/2045772313Y.0000000093. 5. Clarke HF, Bradley C, Whytock S, Handfield 18. Singh R, Rohilla RK, Siwach R, Verma V, Kaur S, van der Wal R, Gundry S.  Pressure ulcers: K. Surgery for pressure ulcers improves general health implementation of evidence-based nursing pracand quality of life in patients with spinal cord injury. tice. J Adv Nurs. 2005;49(6):578–90. https://doi. J Spinal Cord Med. 2010;33(4):396–400. https://doi. org/10.1111/j.1365-­2648.2004.03333.x. org/10.1080/10790268.2010.11689718. 6. Bennett G, Dealey C, Posnett J. The cost of pressure 19. Rubayi S, Burnett CC.  The efficacy of single-­ ulcers in the UK.  Age Ageing. 2004;33(3):230–5. stage surgical management of multiple pres sure sores in spinal cord-injured patients. Ann

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M. Pappalardo et al. 33. Schryvers OI, Stranc MF, Nance PW. Surgical treatment of pressure ulcers: 20-year experience. Arch Phys Med Rehabil. 2000;81(12):1556–62. https://doi. org/10.1053/apmr.2000.17828. 34. Sameem M, Au M, Wood T, Farrokhyar F, Mahoney J. A systematic review of complication and recurrence rates of musculocutaneous, fasciocutaneous, and perforator-­based flaps for treatment of pressure sores. Plast Reconstr Surg. 2012;130(1):67e–77e. https:// 35. Homma K, Murakami G, Fujioka H, Fujita T, Imai A, Ezoe K. Treatment of ischial pressure ulcers with a posteromedial thigh fasciocutaneous flap. Plast Reconstr Surg. 2001;108(7):1990–6; discussion 1997.­200112000-­00023. 36. Janis JE, Kwon RK, Attinger CE. The new reconstructive ladder: modifications to the traditional model. Plast Reconstr Surg. 2011;127(Suppl 1):205S–12S. 37. Levine SM, Sinno S, Levine JP, Saadeh PB. Current thoughts for the prevention and treatment of pressure ulcers: using the evidence to determine fact or fiction. Ann Surg. 2013;257(4):603–8. https://doi. org/10.1097/SLA.0b013e318285516a. 38. Borman H, Maral T.  The gluteal fasciocutaneous rotation-advancement flap with V-Y closure in the management of sacral pressure sores. Plast Reconstr Surg. 2002;109(7):2325–9. https://doi. org/10.1097/00006534-­200206000-­00025. 39. Coşkunfirat OK, Ozgentaş HE.  Gluteal perforator flaps for coverage of pressure sores at various locations. Plast Reconstr Surg. 2004;113(7):2012–7; discussion 2018-9. prs.0000122215.48226.3f. 40. Hong JPJ, Goh TLH, Choi DH, Kim JJ, Suh HS.  The efficacy of perforator flaps in the treatment of chronic osteomyelitis. Plast Reconstr Surg. 2017;140(1):179–88. PRS.0000000000003460. 41. Suh HP, Hong JP. The role of reconstructive microsurgery in treating lower-extremity chronic wounds. Int Wound J. 2019;16(4):951–9. iwj.13127. 42. He J, Xu H, Wang T, Ma S, Dong J.  Treatment of complex ischial pressure sores with free partial lateral latissimus dorsi musculocutaneous flaps in paraplegic patients. J Plast Reconstr Aesthet Surg. 2012;65(5):634–9. bjps.2011.10.001. 43. Parkash S, Banerjee S.  The total gluteus maximus rotation and other gluteus maximus musculocutaneous flaps in the treatment of pressure ulcers. Br J Plast Surg. 1986;39(1):66–71. https://doi. org/10.1016/0007-­1226(86)90006-­8. 44. Ohjimi H, Ogata K, Setsu Y, Haraga I. Modification of the gluteus maximus V-Y advancement flap for sacral ulcers: the gluteal fasciocutaneous flap method. Plast Reconstr Surg. 1996;98(7):1247–52. https://doi. org/10.1097/00006534-­199612000-­00020. 45. Park C, Park BY.  Fasciocutaneous V-Y advancement flap for repair of sacral defects. Ann

39  Reconstructive Options in Wound Care: From Simplest to Most Complex Plast Surg. 1988;21(1):23–6. https://doi. org/10.1097/00000637-­198807000-­00004. 46. Rubayi S, Doyle BS.  The gluteus maximus muscle-­ splitting myocutaneous flap for treatment of sacral and coccygeal pressure ulcers. Plast Reconstr Surg. 1995;96(6):1366–71. https://doi. org/10.1097/00006534-­199511000-­00020. 47. Lin CT, Ou KW, Chiao HY, et  al. Inferior gluteal artery perforator flap for sacral pressure ulcer reconstruction: a retrospective case study of 11 patients. Ostomy Wound Manage. 2016;62(1):34–9. 48. Zhang N, Yu X, Zhao Q, et  al. Rotational repair of pressure ulcer using double-perforators based flaps: a report of 11 cases. J Tissue Viability. 2016;25(4):244–8. jtv.2016.06.003. 49. Koshima I, Moriguchi T, Soeda S, Kawata S, Ohta S, Ikeda A.  The gluteal perforator-based flap for repair of sacral pressure sores. Plast Reconstr Surg. 1993;91(4):678–83. https://doi. org/10.1097/00006534-­199304000-­00017. 50. Allen RJ, Tucker C.  Superior gluteal artery perforator free flap for breast reconstruction. Plast Reconstr Surg. 1995;95(7):1207–12. https://doi. org/10.1097/00006534-­199506000-­00010. 51. Verpaele AM, Blondeel PN, Van Landuyt K, et  al. The superior gluteal artery perforator flap: an additional tool in the treatment of sacral pressure sores. Br J Plast Surg. 1999;52(5):385–91. https://doi. org/10.1054/bjps.1999.3101. 52. Ao M, Mae O, Namba Y, Asagoe K.  Perforator-­ based flap for coverage of lumbosacral defects. Plast Reconstr Surg. 1998;101(4):987–91. https://doi. org/10.1097/00006534-­199804040-­00015. 53. Wilhelmi BJNMP. Surgical treatment and principles. Carbondale, IL: Department of Surgery, Division of Plastic Surgery, Southern Illinois University School of Medicine, E-Medicine; 2008. www.emedicine. com/plastic/topic462.htm. 54. Marchi M, Battaglia S, Marchese S, Intagliata E, Spataro C, Vecchio R. Surgical reconstructive procedures for treatment of ischial, sacral and trochanteric pressure ulcers. G Chir. 2015;36(3):112–6. 55. Lee JT, Cheng LF, Lin CM, Wang CH, Huang CC, Chien SH.  A new technique of transferring Island pedicled anterolateral thigh and vastus lateralis myocutaneous flaps for reconstruction of recurrent ischial pressure sores. J Plast Reconstr Aesthet Surg. 2007;60(9):1060–6. bjps.2007.03.026. 56. Mills R.  Gluteus maximus musculocutaneous flap. In: Strauch B, Vasconez L, Hall-Findlay E, editors. Grabb’s encyclopedia of flaps, vol. 3. London: Little Brown; 1990. p. 1687–8. 57. Tobin GR, Sanders BP, Man D, Weiner LJ. The biceps femoris myocutaneous advancement flap: a useful modification for ischial pressure ulcer reconstruction. Ann Plast Surg. 1981;6(5):396–401. https://doi. org/10.1097/00000637-­198105000-­00009.


58. Labandter HP.  The gracilis muscle flap and musculocutaneous flap in the repair of perineal and ischial defects. Br J Plast Surg. 1980;33(1):95–8. https://doi. org/10.1016/0007-­1226(80)90064-­8. 59. Rubayi S, Chandrasekhar BS.  Trunk, abdomen, and pressure sore reconstruction. Plast Reconstr Surg. 2011;128(3):201e–15e. PRS.0b013e31822214c1. 60. Singh R, Wadhwani J, Rohilla RK, Kaur K. Proximal femoral resection and tensor fascia Lata flap for recalcitrant trochanteric pressure ulcers. Spinal Cord Ser Cases. 2019;5:15. s41394-­019-­0157-­0. 61. Malik R, Pinto P, Bogaisky M, Ehrlich AR.  Older adults with heel ulcers in the acute care setting: frequency of noninvasive vascular assessment, surgical intervention, and 1-year mortality. J Am Med Dir Assoc. 2013;14(12):916–9. jamda.2013.09.004. 62. Bosanquet DC, Wright AM, White RD, Williams IM.  A review of the surgical management of heel pressure ulcers in the 21st century. Int Wound J. 2016;13(1):9–16. 63. Park JS, Lee JH, Lee JS, Baek JH.  Medialis pedis flap for reconstruction of weight bearing heel. Microsurgery. 2017;37(7):780–5. https://doi. org/10.1002/micr.30198. 64. Finkemeier CG, Neiman R. Reverse sural artery pedicle flap. J Orthop Trauma. 2016;30(Suppl 2):S41–2. 65. Grishkevich VM.  Proximally based sural adipose-­ cutaneous/scar flap in elimination of ulcerous scar soft-tissue defect over the achilles tendon and posterior heel region: a new approach. J Burn Care Res. 2014;35(3):e143–50. BCR.0b013e3182a2a74f. 66. Pappalardo M, Jeng SF, Sadigh PL, Shih HS. Versatility of the Free Anterolateral Thigh Flap in the Reconstruction of Large Defects of the WeightBearing Foot: A Single-Center Experience with 20 Consecutive Cases. J Reconstr Microsurg. 2016;32(7):562–70. 67. Rubayi S, Kiyono Y. Flap surgery to cover olecranon pressure ulcers in spinal cord injury patients. Plast Reconstr Surg. 2001;107(6):1473–81. https://doi. org/10.1097/00006534-­200105000-­00026. 68. Bunkis J, Ryu RK, Walton RL, Epstein LI, Vasconez LO. Fasciocutaneous flap coverage for periolecranon defects. Ann Plast Surg. 1985;14(4):361–70. https://­198504000-­00010. 69. Thornton JW, Stevenson TR, VanderKolk CA.  Osteoradionecrosis of the olecranon: treatment by radial forearm flap. Plast Reconstr Surg. 1987;80(6):833–5. https://doi. org/10.1097/00006534-­198712000-­00015. 70. Kokkalis ZT, Papanikos E, Mazis GA, Panagopoulos A, Konofaos P. Lateral arm flap: indications and techniques. Eur J Orthop Surg Traumatol. 2019;29(2):279– 84.­019-­02363-­0.

452 71. Schmidt CC, Kohut GN, Greenberg JA, Kann SE, Idler RS, Kiefhaber TR.  The anconeus muscle flap: its anatomy and clinical application. J Hand Surg Am. 1999;24(2):359–69. jhsu.1999.0359. 72. Lalikos JF, Fudem GM.  Brachioradialis musculocutaneous flap closure of the elbow utilizing a distal skin Island: a case report. Ann Plast Surg. 1997;39(2):201–4. https://doi. org/10.1097/00000637-­199708000-­00017. 73. Ham W, Schoonhoven L, Schuurmans MJ, Leenen LP.  Pressure ulcers from spinal immobilization in trauma patients: a systematic review. J Trauma Acute Care Surg. 2014;76(4):1131–41. https://doi. org/10.1097/TA.0000000000000153. 74. Davies KE, Yesudian P.  Pressure alopecia. Int J Trichol. 2012;4(2):64–8. https://doi. org/10.4103/0974-­7753.96901. 75. Chen N, Zhou M, Dong X, et  al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13. https://­6736(20)30211-­7. 76. Knight D.  Patient positioning in anaesthesia. Continuing education in anaesthesia. Crit Care Pain. 2004;4(5):160–3. 77. Offner PJ, Haenel JB, Moore EE, Biffl WL, Franciose RJ, Burch JM.  Complications of prone ventilation in patients with multisystem trauma with fulminant acute respiratory distress syndrome. J Trauma. 2000;48(2):224–8. https://doi. org/10.1097/00005373-­200002000-­00004. 78. Lucchini A, Bambi S, Mattiussi E, et al. Prone position in acute respiratory distress syndrome patients: a retrospective analysis of complications. Dimens Crit Care Nurs. 2020;39(1):39–46. https://doi. org/10.1097/DCC.0000000000000393. 79. Bloomfield R, Noble DW, Sudlow A.  Prone position for acute respiratory failure in adults. Cochrane Database Syst Rev. 2015;11:CD008095. https://doi. org/10.1002/14651858.CD008095.pub2. 80. Ibarra G, Rivera A, Fernandez-Ibarburu B, Lorca-­ García C, Garcia-Ruano A.  Prone position pressure sores in the COVID-19 pandemic: the Madrid expe-

M. Pappalardo et al. rience. J Plast Reconstr Aesthet Surg. 2020;74:2141. 81. Pappalardo M, Starnoni M, De Maria F, et  al. Secondary autologous fat grafting for the treatment of Chin necrosis as a consequence of prone position in COVID-19 patients. Plast Reconstr Surg Glob Open. 2022;10(11):e4705. GOX.0000000000004705. 82. Coleman SR, Lam S, Cohen SR, Bohluli B, Nahai F.  Fat grafting: challenges and debates. Atlas Oral Maxillofac Surg Clin North Am. 2018;26(1):81–4. 83. Pappalardo M, Davies K, Morley S. Fat Grafting in Facial Palsy: A Secondary Revision Technique to Improve the Facial Aesthetics. Plast Reconstr Surg Glob Open. 2022;10(10):e4572. https://doi. org/10.1097/GOX.0000000000004572. eCollection 2022 Oct. PMID: 36284721 84. Pappalardo M, Montesano L, et al. Immunomodulation in vascularized composite allotransplantation: what is the role for adipose-derived stem cells? Ann Plast Surg. 2019;82(2):245–51. SAP.0000000000001763. 85. Di Stefano AB, Pappalardo M, et  al. MicroRNAs in solid organ and vascularized composite allotransplantation: Potential biomarkers for diagnosis and therapeutic use. Transplant Rev (Orlando). 2020;34(4):100566. trre.2020.100566. 86. Starnoni M, Pappalardo M, Spinella A, et al. Systemic sclerosis cutaneous expression: management of skin fibrosis and digital ulcers. Ann Med Surg. 2021;71:102984. 87. Thamm O, Koenen P, et  al. Autologous fat grafting improves wound healing. Plast Reconstr Surg. 2012;130(2S):485. 88. Rangaswamy M.  Regenerative wound healing by open grafting of autologous fat and PRP-gel—a new concept and potential alternative to flaps. Plast Reconstr Surg Glob Open. 2021;9(1):e3349. https:// 89. Davalbhakta AV, Niranjan NS. Fasciocutaneous flaps based on fascial feeding vessels for defects in the periolecranon area. Br J Plast Surg 1999;52:60.

Surgical Indications in All Diagnostic and Care Pathways (DTCP) Settings


Emanuele Cammarata, Francesca Toia, Antonino Speciale, Martina Maltese, Tiziano Pergolizzi, and Adriana Cordova

40.1 Introduction Conventionally, skin ulcers are defined as tissue lesions that show poor or no tendency to spontaneous healing [1]. Ulcers are frequently encountered in the general population, with an estimated prevalence of about 0.3% at the age of 60 and up to 5% at the age of 90, and occur in patients in all healthcare settings, thus representing one of the most widespread and challenging pathologies in wound care [2]. They have a strong impact on patient’s functional ability and psychosocial well-being [3]. For this reason, appropriate and timely treatment is mandatory in order to reduce the morbidity burden associated with the disease and improve the patient’s quality of life. However, there is still a lack of implementation of evidence-based guidelines for ulcer treatment in daily clinical practice, which leads to poor outcomes. Therefore, in order to provide promptness and continuity of treatments, to ensure high levels of care, and finally to improve the overall management of the pathology, each patient with an ulcer should be included in a diagnostic and therapeuE. Cammarata · F. Toia (*) · A. Speciale · M. Maltese · T. Pergolizzi · A. Cordova University of Palermo, Palermo, Italy e-mail: [email protected]; [email protected]; [email protected]; [email protected]; [email protected]

tic care pathway (DTCP), a predetermined succession of diagnostic and therapeutic activities that encompasses several types of specialists and based on the latest scientific evidence [4]. Considering the complexity and the multiple etiologies of skin ulcers, treatment should be multidisciplinary (dermatologists, general surgeons, vascular surgeons, plastic surgeons, infectiologists, and other clinicians) and tailored to the individual, with the aim of targeting the specific condition. The implementation of a DTCP and the creation of dedicated disease-specific paths, reinforcing collaboration between the territorial services and the hospitals, are the keys to: –– Reduce costs through outpatient and home management of uncomplicated cases. –– Improve outcomes through the selection of complex cases that need referral to a first- or second-level center for surgical treatment [5].

40.2 Etiological Classification and General Assessment Skin ulcers have a complex and multifactorial pathogenesis. They are classified based on etiology into different categories, each with its own typical location, depth, and appearance: venous ulcers, arterial and mixed ulcers, diabetic ulcers, pressure ulcers, traumatic ulcers, inflammatory

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 M. Maruccia et al. (eds.), Pearls and Pitfalls in Skin Ulcer Management,


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and vascular ulcers, and neoplastic ulcers. Ulcers related to venous insufficiency are the most ­common type, accounting for about/almost 70% of cases. Arterial and mixed etiology ulcers represent 10% and 15% of cases, respectively, with the remaining 5% of ulcers resulting from other less common causes [6]. In order of frequency, the most affected body sites are the medial inferior third of the leg, and the medial and the anterior part of the ankle and the foot [3]. To appropriately treat a skin ulcer, an understanding of the pathophysiology of the wound is critical, as each type deserves a specific treatment. Initially, all chronic wounds should be evaluated as stated by the TIME principle, which represents the backbone of treatment: tissue type characterization (epithelializing, granulating, sloughy, and necrotic) detection of infection (contamination, colonization, and local or systemic infection), moisture balance (wet vs. dry, how much exudate is there?), and wound edges assessment (plain, rolled, cliff, and erythematous) [7].

Assessment should start with a thorough clinical physical examination, which can often guide an adequate initial workup. The wound location, size (surface area in cm2), depth, the presence of drainage and tissue type, as well as peripheral pulses should be documented. Some common diagnostic tests might also be performed in order to orient the future treatment: a vascular assessment including ankle-brachial pressure index (ABPI), doppler ultrasound, and/ or angiography to detect venous reflux and/or peripheral arterial disease, a microbiological swab to rule out infection, a tissue biopsy in case of atypical nonhealing wounds with doubt regarding malignancy or rheumatic disease, a rheumatic panel, a blood glucose test including glycated hemoglobin (HbA1c), a urinalysis to assess glycemic control, and a plain X-ray as an initial screening of underlying osteomyelitis, followed by eventual CT/MRI scan [4, 8]. After these general measures are done, the ulcer must be correctly diagnosed and classified by suspected etiology, so that appropriate care can be provided (Table 40.1).

Table 40.1  Etiological classification of skin ulcers Ulcer type Venous




Traumatic Neoplastic


Typical appearance and location • Shallow ulcer • No eschar • Located in the gaiter region (often over the medial aspect of the leg) • Superficial or deep • Located over bony prominences (sacrum and heels) or other areas subjected to unrelieved pressure • A deep ulcer that appears “punched-out,” with well-demarcated borders • Pale, non-granulating base • +/− Eschar • +/− Exposure of deep structures • Located over toes and heels • Superficial to deep • Extensive callus formation • +/− Associated deformity • Located in the hand and foot (stocking and glove distribution) • Located in an area of previous trauma or burns • Rolled edges • Located in the context of an area of chronic inflammation or scarring (chronic wounds, burn injuries, venous ulcers, osteomyelitis, and radiation dermatitis) • Often symmetrical • Irregular edges • Associated satellite lesions • Located in the inner side of the lower limbs • Often very painful

40  Surgical Indications in All Diagnostic and Care Pathways (DTCP) Settings

40.3 Common Principles of Treatments In the management of skin ulcers, the treatment of the underlying pathology is always mandatory, but a regular approach, that is common for every type of ulcer, can be outlined/schematized as follows/consists of four important steps.


pressure water jet dissection (hydrosurgical debridement) [9, 10] (Fig. 40.1).

40.3.2 Infection Control

Treatment of associated infection (if present) is another key element in ulcer management. Infection is generally controlled with topical agents, including dressings with silver, polyhexamethylene biguanide, and cadexomer iodine. Antimicrobial washes may also be beneficial if 40.3.1 Debridement the presence of a biofilm is suspected. If signs of Debridement is the removal of dead cells and systemic infection or cellulitis are present, sysbacterial biofilms and is the first-line treatment temic antibiotics may also be indicated. for skin ulcers, representing a key factor in wound Moreover, hyperbaric oxygen therapy (HBOT) healing. Several different types of debridement can be useful as an additional anti-infective agent are available: autolytic, enzymatic, biologic, and [11, 12]. Final reconstruction is usually deferred surgical, using either sharp technique or high-­ after negative results of antimicrobial swabs. a




Fig. 40.1  Surgical debridement of a venous ulcer on the lateral malleolar region. (a) Preoperative picture. (b) Intraoperative marking of the entire surface of the ulcer with blue methylene dye. (c) Mechanical sharp debride-

ment with a Volkmann spoon. (d) “Radical” debridement of the ulcer through complete removal of the methylene blue dye from the wound bed

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40.3.3 Wound Bed Preparation (WBP) Preliminary wound bed preparation is crucial for a successful reconstruction. It can be performed with advanced medications and/or negative pressure wound therapy (NPWT) [13–16].

40.3.4 Wound Closure Wound closure is the final step of ulcer management. Healing can be achieved by secondary intention, through re-epithelialization from the margins of the wound or the skin appendages, or by first intention or reconstruction in one or more surgical stages, using dermal substitutes, grafts, and different types of local and free flaps. Nevertheless, each ulcer subtype deserves a specific treatment based on its etiology, and some reconstructive procedures could be not indicated in certain ulcer subtypes. For example, skin grafts are a valid option in case of venous ulcers but are not appropriate in case of deep pressure ulcers, which need to be reconstructed with well-vascularized tissue, in order to provide thickness and fill dead spaces. In this case, locoregional or free flaps are the technique of choice, and, as a general rule, cutaneous or fasciocutaneous flaps are preferred at first while muscular flaps are considered as a second lifeboat option in case of reconstructive failure [17]. However, a thorough description of ulcer-­ type-­specific reconstructive techniques is not the subject of this paragraph and will be further provided below.

40.4 Indications for Hospital Surgical Referral in the DTCP After a first assessment in primary care settings, patients with uncomplicated ulcers are usually managed by the general practitioner and successfully treated at home by community nurses. In selected difficult cases, when healing is not obtained with basic methods, the management of

skin ulcers should be addressed in a timely way at a specialized first- or second-level center for a more extensive and structured treatment by a coordinated multidisciplinary team [3]. Particularly, the following conditions require referral to a specialized center/unit for surgical treatment: –– Non-healing ulcers: ulcers not following expected healing progression within 6 weeks (no or poor improvement in ulcer measurement), defined as less than 40% reduction in surface area, with a standard pathway of care consisting in best management of wound through conventional dressings. –– Ulcers greater than 6  months old at first diagnosis. –– Large ulcers (greater axis >10 cm or surface >100 cm2). –– More than three episodes of local wound bed infection. –– Rapid deterioration of the ulcer. –– Osteotendinous exposure. –– Gangrene after revascularization. –– Suspected malignant ulcer in which a skin biopsy is mandatory to rule out cancer. –– Recurrent ulcers, regardless of the previous criteria [5, 18–20].

40.5 Specific Recommendations Based on Ulcer Subtype 40.5.1 Venous Ulcers Venous ulcers of the lower limbs (VLU), identified as stasis ulcers, stasis dermatitis, or varicose ulcers, are the most severe and devastating form of chronic venous disease (CVD) and account for about 80% of lower extremity ulcerations. VLU affects approximately 1% of the general population in most countries, and the incidence rate increases with age and female gender [21]. They are classically located over the medial aspect of the leg but may also extend circumferentially in severe cases. In the clinical view, venous ulcers occur due to “pure” venous causes, or due to “mixed” causes, as in cases in

40  Surgical Indications in All Diagnostic and Care Pathways (DTCP) Settings

which arterial ischemia, lymphedema, autoimmune disease, local trauma, infection, and other processes coexist with venous hypertension. The mixed ulcers often have a different rate of healing and demand additional treatment beyond the appropriate venous measures for healing to occur [22]. Operative Management At first, a surgical debridement should be always performed to remove superficial necrotic tissue, and excessive bacterial and cellular burden of dead and senescent cells. In the case of non-infected venous ulcers, it is not necessary to prepare the wound bed using negative pressure devices, and the reconstruction can be performed in a single surgical step. A skin graft is the more common reconstructive surgery for shallow venous ulcers. However, dermal substitutes are a feasible option too, espea


Fig. 40.2  Case of chronic venous leg ulcer in a 70-year-­ old man with venous insufficiency, peripheral arteriopathy, and lymphatic drainage dysfunction. (a)


cially in the case of deep ulcers, because they can provide a better morphological result through the augmentation of dermal thickness [23]. A correct grafting procedure should follow some important principles: –– Graft adherence to the wound bed with no tenting effect through the preparation of a smooth wound bed surface. –– Sterility and infection control with Argentum-­ based antimicrobial wound dressings. –– Adequate compression with foams. –– Strong fixation of the graft and immobility through the use of counterposed stitches. –– Non-adherence of the dressing at removal. Finally, the treatment of the associated venous perforator incompetence by ligation could be useful for complete recovery and normalization of the venous pressure [24] (Fig. 40.2). c

Post-debridement ulcer. (b) Postoperative picture 1 week after reconstruction with a skin graft. (c) Final result 1 month after surgery

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40.5.2 Pressure Ulcers Pressure ulcers (PU) are localized lesions that generally occur as a result of unrelieved and prolonged pressure over bony prominences causing damage to the skin and/or the underlying tissues. They usually occur in patients who have reduced mobility and spend the majority of their time lying in a bed or in a wheelchair without shifting their bodyweight. This means that all patients who are critically unwell in the hospital setting are potentially at risk [25, 26]. PU is more common in case of coexisting additional risk factors (e.g., paralysis, peripheral vascular disease, decreased sensation, poor nutritional status, cognitive impairment, and frailty) [25–27]. If a patient is confined to bed, the most frequent areas are the sacrum, the coccyx, the trochanteric region, and the calcaneus, whereas, if a patient has prolonged periods of sitting in a chair, the coccyx and the elbows are the areas at higher risk [28]. Pressure ulcers can present as open ulcers or can arise on the surface of intact skin, showing the “tip of the iceberg” effect, where the skin surface is relatively spared compared to the underlying tissue. This is because necrosis often starts at the site of the highest pressure, which is at the bone/muscle interface. Accordingly, a pressure ulcer may be much more severe than first thought because the damage to the deeper tissues is not reflected at the surface [29] (Fig. 40.3).

PU are classified into four stages based on their thickness [30]. National Pressure Ulcer Advisory Panel’s staging system is provided in Table 40.2. Operative Management Negative pressure wound therapy (NPWT) is not routinely used but can be a useful option for ulcers with high levels of exudate requiring multiple dressing changes a day and for stage 3 or 4 ulcers. NPWT can help optimize the wound bed for surgical closure or stimulate healing while waiting for reconstructive surgery. Ulcerectomy, debridement, and eventual bone resection are indicated to remove fibrous scars and potentially infected tissue, with the aim of preventing relapses. Table 40.2  National Pressure Ulcer Advisory Panel’s updated pressure ulcer staging system Stages Stage 1: non-­ blanchable erythema Stage 2: partial thickness skin loss Stage 3: full thickness skin loss Stage 4: full thickness tissue loss Unstageable: depth unknown

Fig. 40.3  Ischiatic ulcer in 60-year-old paraplegic patient

Clinical appearance Skin is intact with non-blanchable redness localized to an area usually over bony prominence. The area may be painful, firm, soft, warmer, or cooler than adjacent tissue. Partial thickness loss of dermis presenting as a shallow ulcer with a pink wound bed. Ulcer in which subcutaneous fat may be visible with or without slough. However, bone, tendon, or muscle are not visible. Ulcer in which muscle, tendon, or bone is exposed. Ulcer often includes undermining or tunneling; hence, it is at risk of causing osteomyelitis. Ulcer in which base is covered by slough or necrotic tissue; therefore, true depth cannot be determined and therefore classified. Deep tissue injury presents with a purple or maroon localized area of discolored skin or blood blister as a result of damage to underlying soft tissue. In darker skin types, it may be difficult to detect whether non-­ blanching skin erythema is present, such as in stage 1 ulcers or a deep tissue injury, so high suspicion of risk is required.

40  Surgical Indications in All Diagnostic and Care Pathways (DTCP) Settings

Intraoperative bone specimens should be obtained for microbiological culture when osteomyelitis is suspected. The removal of bony prominences is recommended to help relieve pressure points. Care must be taken, however, not to remove bone in excess, because this may expose critical deep structures or produce new unnatural weight-bearing skin surfaces [31, 32]. Although there are no recommendations regarding a specific type of surgery for this type of ulcer, reconstruction should provide functional weight-bearing coverage. Generally, skin grafts are not indicated because they do not typically provide enough strength or bulk to cover the wound. The primary closure of relatively small stage 2 or 3 ulcers may be attempted when immediate closure is desired. While this relatively simple procedure can be performed, wound dehiscence is a common complication [33]. For more extensive stage 3 or 4 pressure ulcers, surgical management with a regional or free flap is mandatory in order to fill dead space. Cutaneous and fasciocutaneous flaps are generally preferred over muscle flaps, which are generally preserved for recurrent cases or in case of reconstructive failure as a lifeboat option [34, 35] (Fig. 40.4). a


Fig. 40.4  Operative photographs showing the patient in a prone position with an ischiatic ulcer. (a) Pre-operative drawing. (b) Advancement of the V–Y flap. (c) Complete


40.5.3 Arterial Ulcers Arterial ulcers (AU) usually develop from an imbalance in arterial blood flow: a reduced/inadequate perfusion of the skin and soft tissues leads to/causes ischemia and subsequent necrosis, finally resulting in ulceration. The main cause is represented by peripheral vascular disease/ chronic obstructive disease due to atherosclerosis, diabetic macro- and micro-angiopathy, vasculitis, and microthrombi [36]. If compared to venous ulcers, AU are preferentially located more distally, typically on the foot (toes, metatarsals, and calcaneus) or, less frequently, in the anterolateral region of the leg distal third [37]. AU has a characteristic “punched-out” appearance, well-demarcated edges, and a pale bottom. They can present with an eschar on their surface and deeper structures, such as fascia, tendons, and muscles may be involved too. The surrounding skin appears pale, atrophic, and hypothermic with altered skin adnexa (decreased number of hair). The striking clinical clue is jolting, burning pain, and functional impotence, increased in the supine position. The most important diagnostic tool in the evaluation of the arterial nature of an ulcer is repc


dissection of the perforator flap. (d) Clinical picture 10 weeks after surgery, showing complete healing of the flap

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resented by the ankle-brachial pressure index (APBI): an ABPI