Alexandria wound care manual: Audit guide for beginners

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ALEXANDRIA WOUND CARE MANUAL

Disclaimer This book is just a review of literature of wound care, no part of it is genuine (except for some small parts) We managed to mention every copyright and every reference as much as possible. We tried -with this book- to open the door of wound care knowledge for middle east medical staff and students, and to show them the evidence-based knowledge. This book is not and will not be for any financial benefit. We do not expect any demands about any copyrights because we do not pretend, we have any in this book, anyone can copy or take any part from it without permission as if he/she mention the original source.

The pictures and illustrations inside this book are not ours and are not genuine. We do not pretend that we own it we transferred it from the

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TEXT ATLAS OF WOUND MANAGEMENT EDITED BY VINCENT FALANGA TEXT ATLAS OF WOUND MANAGEMENT CHRISTINA LINDHOLM POLLY A. CARSON JAYMIE PANUNCIALMAN LISA MAMAKOS TIZIANA N. LOTTI JANE K. FALANGA I stock site https://www.google.com/search?q=skin+anatomy+and+physiology&rlz=1C1FHFK_enEG938EG938&source=l nms&tbm=isch&sa=X&ved=2ahUKEwi4177R_636AhUssaQKHcB2DuIQ_AUoAXoECAEQAw&biw=1366 &bih=657&dpr=1#imgrc=s41qfJI7bUkngM https://www.google.com/search?q=structure+of+ebiderms&tbm=isch&ved=2ahUKEwj8mI7T_636AhUK2KQ KHRb6DK8Q2cCegQIABAA&oq=structure+of+ebiderms&gs_lcp=CgNpbWcQAzoECAAQEzoICAAQHhAHEBM6CAgAE B4QCBATOgQIABBDOgUIABCABDoKCAAQsQMQgwEQQzoECAAQHjoGCAAQHhAFOgYIABAeEAh Q8whYncUYJzvFGgAcAB4AIABogSIAZEekgEKMC4xOC4zLjUtMZgBAKABAaoBC2d3cy13aXotaW1nsAEAwAE B&sclient=img&ei=M0QvY7yzAYqwkwWW9LP4Cg&bih=657&biw=1366&rlz=1C1FHFK_enEG938EG938 #imgrc=3UbfVgDSa8RoBM&imgdii=M8wwLJf2yC1dOM H Tao, JP Butler, T Luttrell - … of the American College of Clinical Wound ..., 2012 – Elsevier Comparison of Bulb Syringe and Pulsed Lavage Irrigation with Use of a Bioluminescent Musculoskeletal Wound Model Major Steven J. Svoboda, Terry G. Bice, Heather A. Gooden, Daniel E. Brooks, Darryl B. Thomas and Joseph C. Wenke J. Bone Joint Surg. Am. 88:2167-2174, 2006. doi:10.2106/JBJS.E.00248 Wound Debridement with 25 kHz Ultrasound Margaret McCarty Stanisic Froedtert Memorial Lutheran Hospital Barbara Provo Sinai Samaritan Medical Center, Milwaukee David L. Larson Medical College of Wisconsin Luther C. Kloth Marquette University, [email protected] https://www.google.com/search?q=foam+dressing&tbm=isch&ved=2ahUKEwjmvHm6Kb6AhXOnaQKHQI9CDkQ2cCegQIABAA&oq=foam+dressing&gs_lcp=CgNpbWcQAzIECAAQQzIFCAAQgAQyBggAEB4QBzIGCAA QHhAHMgYIABAeEAcyBggAEB4QBzIGCAAQHhAHMgYIABAeEAcyBggAEB4QBzIGCAAQHhAHUN0 MWIoaYJQmaABwAHgAgAH_AogB1weSAQcwLjQuMC4xmAEAoAEBqgELZ3dzLXdpei1pbWfAAQE&s client=img&ei=uIArY-a-E867kgWC-

qDIAw&bih=657&biw=1366&rlz=1C1FHFK_enEG938EG938#imgrc=99AiUBUyvWx83M&imgdii=9ckrvyfl E1frxM 9. RIII Dioso, K Judenimal, G Arunaj - Journal for Research| Volume, 2017 - academia.edu 10. Polymeric and Natural Composites book Md Saquib Hasnain Amit Kumar Nayak Saad Alkahtani 11. Z Hussain, HE Thu, AN Shuid, H Katas… - Current drug …, 2018 - ingentaconnect.com 12. https://www.google.com/search?q=fibrous+patches+dressing&tbm=isch&ved=2ahUKEwjSoLe5k8X6AhVNu KQKHcUtDBwQ2cCegQIABAA&oq=fibrous+patches+dressing&gs_lcp=CgNpbWcQA1AAWOUiYOsqaAJwAHgAgAHGAYg BgASAQQwLjEzmAEAoAEBqgELZ3dzLXdpei1pbWfAAQE&sclient=img&ei=92c7Y5LJNM3wkgXF27DgAQ& bih=600&biw=1366&rlz=1C1FHFK_enEG938EG938#imgrc=qPpwFczZEMwF-M 13. https://www.google.com/search?q=chitoderm+dressing&rlz=1C1FHFK_enEG938EG938&source=lnms&tbm=i sch&sa=X&ved=2ahUKEwie4eyIkcX6AhVO2KQKHcAuDy8Q_AUoAXoECAIQAw&biw=1366&bih=600& dpr=1#imgrc=vu-Ay_yKVauWBM 14. https://www.google.com/search?q=hemcon+dressing&rlz=1C1FHFK_enEG938EG938&oq=hemcon+drss&aqs =chrome.1.69i57j0i13i19i512j0i8i13i19i30l4.10048j0j15&sourceid=chrome&ie=UTF-8#imgrc=TLMmWr2dEH1XM 15. https://www.google.com/search?q=chitoderm+dressing&rlz=1C1FHFK_enEG938EG938&source=lnms&tbm=i sch&sa=X&ved=2ahUKEwie4eyIkcX6AhVO2KQKHcAuDy8Q_AUoAXoECAIQAw&biw=1366&bih=600& dpr=1#imgrc=_pr_7p3IspAvLM 16. https://www.google.com/search?q=celox+dressing&tbm=isch&ved=2ahUKEwjX67ORkcX6AhVHOewKHTS uAhgQ2cCegQIABAA&oq=celox+dressing&gs_lcp=CgNpbWcQAzIHCAAQgAQQEzIICAAQHhAHEBM6BggAEB 4QB1CyEliNHWDfLmgAcAB4AIABlAGIAa8GkgEDMC42mAEAoAEBqgELZ3dzLXdpei1pbWfAAQE&scl ient=img&ei=i2U7Y5f6AsfysAe03IrAAQ&bih=600&biw=1366&rlz=1C1FHFK_enEG938EG938#imgrc=kH wTvn2MnrNh_M 17. Biopolymer and Synthetic Polymer-Based Nanocomposites in Wound Dressing Applications: A Review Ravichandran Gobi 1, Palanisamy Ravichandiran 2,3,4 , Ravi Shanker Babu 1,* and Dong Jin Yoo 2,3,4,* 18. https://www.researchgate.net/figure/A-Images-of-the-skin-wound-dressing-compared-in-three-groups-hydrogelprecursor_fig4_333692638 19. https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8735859&blobtype=pdf 20. CK Sen, S Khanna, G Gordillo, D Bagchi… - Annals of the New …, 2002 - Wiley Online Library 21. H Kaufman, M Gurevich, E Tamir, E Keren… - journal of wound …, 2018 - magonlinelibrary.com 22. Use of negative pressure wound therapy in burn patients Shou-Cheng Teng Department of Plastic and Reconstructive Surgery, Tri-Service General Hospital, Taipei City, Taiwan 23. Electrical Stimulation Technologies for Wound Healing Luther C. Kloth* Physical Therapy Department, College of Health Sciences, Marquette University, Milwaukee, Wisconsin. 24. W Lyu, Y Ma, S Chen, H Li, P Wang… - Advanced …, 2021 - Wiley Online Library 25. YR Kuo, CT Wang, FS Wang… - Wound Repair and …, 2009 - Wiley Online Library 26. J Dissemond, B Assenheimer… - JDDG: Journal der …, 2016 - Wiley Online Library 27. Efficacy of Low Level Laser Therapy on Wound Healing in Patients with Chronic Diabetic Foot Ulcers—A Randomised Control Trial

To the naïve reader, we mentioned every reference possible and we do not expect any legal issues about it.

Contents 1

Introduction

2

Chapter 1

3 4

5 6 7

8 9 10

11

History Of Wound Care

Chapter 2 Wound Healing

Chapter 3 Wound Management

Chapter 4 Introduction To Wound Dressing Material

Chapter 5 Natural Wound Dressing Material

Chapter 6 Synthetic Wound Dressing Material

1 47

51 96

188

216

254

Chapter 7 Polymer Composition

263

Chapter 8 Types of Dressing According To Sensitivity To Stimulus

285

Chapter 9 Types of Dressing According To Charge Of Polymer

295

Chapter 10 Drug Loaded Wound Dressing

314

12

13

14

15 16

17

18

19

20

21

22

23

Chapter 11 Antiseptics And Local Antibiotics

330

Chapter 12 Other Modalities Of Treatment

339

Chapter 13 Wound Management In Psychiatric Patient

370

Chapter 14 Psychiatric Illness And Wound Healing

Chapter 15 Wound Healing In Pediatric Age

Appendix 1 Story Of The Book

Appendix 2 Quality Of Life & Systemic aapproach to manage a complex wound

Appendix 3 Special Procedures

Appendix 4 Braden Scale – For Predicting Pressure Sore Risk

Appendix 5 Preferences Of Patients, Doctors, And Nurses Regarding Wound Dressing

Appendix 6 Wound Dressing Selection For Residential Aged Care

Appendix 7 Burn

373 380 403

409

414 419

421

422

424

24

25

26

Appendix 8 Diabetes

Appendix 9 Studies

Appendix 10 Nanotechnology

27

Questionnaire

28

References

۞ 28

Volume 2 (A separate handbook) Audit Guide For Beginners

425

432 439 477

478

WOUND CARE MANUAL FIRST EDITION

Editors Ibrahim Ahmed Muhammed Elsherbini General surgeon , Alexandria Medical Research Institute , Alexandria University MSc Degree in Clinical and Experimental Surgery MRCS Eng [email protected] https://orcid.org/0000-0002-1727-4476 To the sun and to the moon, Pearl and lilly, the ground and water, the Belt of Orion, the little cloud, the ADHD, my pipe that never smoked, Nobel Prize that is soon to come, Mitochondria, Xenobots and Transposons

Mustafa Mohamed Abdelfatah Elkamah

Nourhan Mohamed Fahim Abdallah

Intern, Alexandria Main University Hospitals [email protected] "A MAN DOESNOT STAND ALONE" -CRESSY MORRISON- , So once we are existed , we are motivated to learn and search. This dedication is for all dears, colleagues and for all those searching.

Intern, Alexandria Main University Hospitals [email protected] https://orcid.org/0000-0001-6297-2284 To all the people who are loving and kind to me. Thank you for the sunshine you bring into my life

Omnia Hussein Ibrahim Mostafa Intern, Alexandria Main University Hospitals [email protected] I dedicate this to my mum and my dad, my corner stone. Thank you for everything you have done for us

Nada Metwally Mohamed Ahmed Intern, Alexandria Main University Hospitals [email protected] To my parents, for always loving and supporting me

Mohamed Osama Mohamed Hassan Hassan Intern, Alexandria Main University Hospitals [email protected] We All Have Dreams, But in order To Make Dreams Come true, It takes an awful lot of determination, dedication, SelfDiscipline and effort", I dedicate this to my beloved family, my dear colleagues and to my dear patients of Almeri hospital, I Hope it makes a big difference in alleviating the pain you are experiencing, and like I always say, "It always seems impossible until it's done"

Wafaa Mahmoud Gomaa Abdellatif General practitioner [email protected] Allah the all merciful, I beg Thee To accept this effort For the soul of my mother, She was your gift for me

Hala Yasser Gaber Abd El Fatah Intern, Alexandria Main University Hospitals [email protected] I dedicate this to my mother, the spine for me , my father who represents my four limbs and my sisters who are the spirit of life

Eiman Wael AbdEl Aziz ElSayed Intern, Alexandria Main University Hospitals [email protected] I dedicate this to my parents and more importantly my sister, my amazing supporting system, Thank you

Omnia Alaa El-Din Abd El-Salam Ali General practitioner [email protected] To my first love and pride.......My late father To my family I owe you everything To my mentors I will always be your grateful student

Eman Essam Hamed Hassan Elhofy General surgery resident ،Medical Research Institute , Alexandria University MRCS Eng [email protected] To my hidden fear settled behind what we have created as traditions and customs, I wish you can come and see what I have done till the moment and what I am wishing to achieve So, from the bottom of my heart, please keep resting in peace for the rest of my life

Ahmed Mohamed Mahmoud Anany Intern, Alexandria Main University Hospitals [email protected] To Joud, our hope and blessing from above and her endlessly giving grandparents

Dedicated to my supporting system my parents, my brothers, my sister and my husband, thank you

Mahmoud Bassiony Final year Medical Student [email protected] I am really grateful for this opportunity and I want to thank my colleagues and workmates who have believed that I can contribute to this book.

Faisal Gamal Abdulghani Hemeda Ibrahim MBBS , MRCP Wexham Park Hospital, Slough, UK [email protected] To my dad the great physicist who made the stars in my hands, to my mom who made me a man. To my wife and my daughters.

Nourhan Elsaid Mahmoud Awad Intern, Alexandria Main University Hospitals [email protected] This work is dedicated to my little family ; my dearest father God bless him, my mom, my sisters and my friends

Mayar Ibrahim Elsayed Abdalla

Abdelrahman Mohamed Abdelmoniem Tawfik

Mennatallah Mohammed Ali Hosni Shalabi

3rd Year Medical Student Faculty of Medicine, Alexandria University [email protected] With much appreciation, this is dedicated to my mother for her abundant support, tenderness, and understanding

Menatalla Salem Abdel Aziz Salem Asem Intern, Alexandria Main University Hospitals [email protected] I'd like to dedicate this work to my family for their unlimited support and encouragement. I'd also like to thank my friends for offering me help and guidance during this journey

Aml Ayman Romieh Intern, Alexandria Main University Hospitals [email protected] I dedicate this to my sister, my cat and friends who make my journey more worthy and give ultimate support

Pancee Essam Ahmed Shaheen Intern, Alexandria Main University Hospitals [email protected] Thank you god for blessing me more than I deserve

Moshera Isamael Hussien Ismael Radwan Intern, Alexandria Main University Hospitals [email protected]

Intern, Alexandria Main University Hospitals [email protected] To the supporters ,careers and givers Mamitto and Daditto

Intern, Alexandria Main University Hospitals [email protected] This is dedicated to my beloved parents and family who have been my source of light, inspiration and strength

Maha Magdy Mohamed Intern, Alexandria Main University Hospitals [email protected] To my biggest supporter, who keep saying “I am proud of you" in my failure before my success. To my father

Aml Ali Attia Ibrahim Intern, Alexandria Main University Hospitals [email protected] I dedicate this to my parents and my best friend who make my journey more worthy and give ultimate support

Maya Mohamed Magdy Ahmed Shalaby Intern, Alexandria Main University Hospitals [email protected] Dedicated to physicians and the positive impact they have on the lives of their patients

Mohamed Ibrahim Mohamed Ahmed

Eslam Alaa Abdelaziz Abdelwahab Hassan

Intern, Alexandria Main University Hospitals [email protected] To the person who constantly prays for me, the person who inspires me, who is also my role model. My mother

General surgeon at Medical research institute Alexandria University [email protected] This project is dedicated to the young surgeons They are the future of medicine as every generation should be better than the former one

Hala Hassan Ibrahim Hassan Intern, Alexandria Main University Hospitals [email protected] All thanks to my parents for their support and warm wishes I hope they lead a healthy life full of happiness

Marwan Emad Abdalla Ahmed Abdou General surgery resident Medical Research Institute, Alexandria University [email protected] I would like to convey my most sincere gratitude to my professors, for their unlimited help, continuous guidance and support throughout the whole project

Alyaa Abdelkhalek Saad Sabra Intern, Alexandria Main University Hospitals [email protected] Dedicated to my supportive family, my mother, my father, my sister, my brothers and my partner

Toka Ahmed Ibrahim Elsehemy Intern, Alexandria Main University Hospitals [email protected] To my exquisite mother, the one that never let me down. I owe you everything.

Ahmed Samir Ibrahim Arab Intern, Alexandria Main University Hospitals [email protected] To my beloved mother, the most important woman in my life, I wouldn’t be who I am today if it wasn’t for your support and help. I owe you my past, present and future. With all my heart, Thank you

Ibrahim Ahmed Ibrahim Sidahmed Sarhan Intern, Alexandria Main University Hospitals [email protected] I would like to dedicate this work to my family and thank them for their constant support.

Peter Ashraf Fayez Guirguis Cardio thoracic surgeon Alexandria University Hospital [email protected] To the God's hand, to the support of my beloved family and finally to my mentors. I can't express my appreciation for your love, support and encouragement.

Fouad Mohamed Fouad Ashoush Senior Clinical Fellow in Endocrine & General Surgery Royal Victoria infirmary The Newcastle upon Tyne Hospitals NHS Foundation Trust [email protected] This book conveys basic knowledge and required skills for all of my junior colleagues I hope this work helps them in their career and practical life

Zainab Galal Abdullah Emara Intern, Alexandria Main University Hospitals [email protected] Thank you both for giving me strength to reach for the stars and chase my dreams

Mahmoud Mohamed Mahrous Abo Khalil Intern, Alexandria Main University Hospitals [email protected] Dedicated to my parents, my sisters and my wife. Thank you for everything

Omar Medhat Dawood Mahmoud Intern, Alexandria Main University Hospitals [email protected] To my family. To my mother: for always being the person I could turn to during those dark and desperate years. She sustained me in ways that I never knew that I needed. To my father, brother and sisters thank you for letting me know that you had nothing but great memories of me. So thankful to have you back in my life. Finally, to all those who have been a part of my getting there: my professors and colleagues

Muhammad Mohieddin Ghorab Radiologist at students' university hospital [email protected] https://orcid.org/0000-0002-2799-4645 For my family who are always there for me

Special thanks to Dr. Muhammad Ghorab for his great contribution to this book

Contributors Design and layout by Omnia Alaa El-Din Abd El-Salam Ali General practitioner [email protected] To my first love and pride.......My late father To my family I owe you everything To my mentors I will always be your grateful student

Arabic layout by Aml Ayman Romieh Intern, Alexandria Main University Hospitals [email protected] I dedicate this to my sister, my cat and friends who make my journey more worthy and give ultimate support

Introduction Nourhan Mohamed Fahim , Mohamed Osama Hassan , Ibrahim Ahmed Elsherbini

Wound Dressing Wound Assessment & Management Guidelines

Wound assessment -

Purpose - To ensure the correct assessment and management of patients with wounds

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Introduction - Choosing a wound dressing depends greatly on a holistic assessment of the patient and their wound - Presenting Complaint - Past Medical History - Etiology / Cause of wound Eg Inflammatory condition, pressure, revascularization - Control or Remove or Reconstruct - Wound History - The patient should be at the centre of all care decisions made. - Wound assessment should be a systematic process accurately documented on the wound assessment and management care plan. - Dressings should be selected from the Trust Wound Care Formulary unless otherwise advised by a specialist - Patients with complex needs should be referred to the most appropriate speciality.

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A documented holistic and wound assessment should be done as soon as possible after admission to the caseload. The evaluation does not need to be completed at every dressing change if there is little change in the wound condition but document “no change in wound condition”. Dressing change must be recorded. Progress of the wound must be fully reassessed and documented. Any deteriorating wound must have a full re-assessment/evaluation completed and action taken In the case of a chronic wound (at 2-4 weeks), the wound should be reassessed weekly (every two weeks at a minimum)

Completion guide for wound assessment 1. Patient details & date of initial assessment - All details must be completed. 2. Type of wound: - Circle the relevant box 3. How long has the wound been present? - Write length of duration, not the date when the patient came on caseload unless they coincided. 4. Factors which may delay wound healing: - Tick all relevant boxes, add extra information as appropriate (check patient’s medical notes).

Responsibilities - All health care professionals involved in the direct assessment and management of wounds.

1

5. Medications: - Tick all relevant boxes, add extra information as appropriate. 6. Date referred to: - Tick all relevant boxes; discuss referrals with colleagues and GPs. Do not over-refer to similar specialities, e.g., plastics, dermatology, tissue viability 7. Drawing/photograph - Please illustrate wound. Use photography (verbal or written consent) – tape measures are available in the dressing packs. Write date, take a minimum of two photographs: one to situate the wound on the body and one closer to the wound. Download and attach to SystmOne or protected system used. 8. Location of wound/s: - Please indicate on body map where the wound is situated. 9. Wound dimension - Please measure as accurately as possible or indicate if this is an estimation. - Length = head to toe furthest points, measured in centimeters. - Width = side to side furthest points, measured in centimeters. - Depth = may be estimated as very difficult to assess safely and accurately. A sterile gloved finger or wound swab can be used to probe. - Category PU = if the wound is a pressure ulcer, please indicate its category. - Undermining = area tracking, measure with a probe and indicate direction. 10. Wound bed - Please estimate percentage of different tissue type in each box. 11. Suture/clips - Specify and indicate removal date. 12. Exudate levels - Please complete using the following guidelines:

2

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High = needs daily or more dressing changes and saturated each time. - Moderate = needs dressing changes every 2-3 days and soiled but not soaked. - Low = needs weekly or less dressing changes and dressing dry or minimally soiled. 13. Wound edges/surrounding skin: - Please indicate as outlined. 14. Pain - Please assess patient and indicate action. Please refer for medical intervention/pain team. 15. Clinical signs of infection - Please indicate and swab if necessary. If the patient is at risk of developing an infection, ensure that daily vital signs are taken. 16. Treatment objectives - These objectives should be suitable for most patients, but a more individualised care plan may need to be added. Use the appropriate objectives according to the phases of healing. 1) Patient comfort – although could be used for most patient’s wound care it is more suitable for “end of life” patient where no active treatment (e.g., debridement) may not be suitable. Can be associated with odour control. 2) Absorption: for wound with large exudate where the main objective is containing the fluid. 3) Infection control: for infected wound. It can be associated with odour control 4) Odour control: see above 5) Debridement: active treatment 6) Promote granulation: active treatment – post or concurrent to debridement 7) Promote epithelialisation: active treatment – concurrent to granulation

Factors which may delay wound healing (tick if present, tick nil identified if no factors present) Medical Medications Conditions Rheumatoid Immobility Steroids Arthritis Diabetes Mellitus Incontinence Immunosuppressive

17. Cleansing solution - Please document saline or water. Other solutions are not recommended unless required for a specific clinical need. - Clean thoroughly surrounding skin and wound to remove some slough, dressing debris or exudate. 18. Dressing choice - Choose from the Wound Care Formulary, review wound progress or deterioration and document the rationale for dressing changes during period of care. 19. Frequency of dressing change - Please document, dependent on exudates, dressing used and progress of wound. 20. Signed/print name/designation - This is a legal requirement and must be accompanied by printing name legibly if using paper.

Cardiac Disease Anemia Chronic respiratory disease Venous/Arterial Disease Decreased sensation

Infection Obesity Malnutrition

Biologics Anti-coagulants Cytotoxics

Poor nutrition Smoking

Allergies

Alcohol

Non-steroidal antiinflammatory Other ……………………… … Nil identified……………

Skin sensitivities

Concordance Issues Please specify ……. ……………..

Severe acquired immune defects

Wound assessment and Management chart Name Address Tel DOB

Hospital record GP/Surgery DN Team Ward

Tel Tel Tel

Standard: In conjunction with Trust Wound Care Guidelines, an assessment and care plan should be completed for all patients with wounds. Date of Initial Assessment Type of Wound(s) (Please circle) How long has wound been present? Date referred to: Dermatology …./.…./…. Plastic Surgeon …../…../…..

Pressure Ulcer Grading

DD/MM/YY Leg Ulcer

Moisture Lesion

Surgical

Tissue Viability Team ...…/.…./…. Podiatry/Foot Team …../…../….. Others …../…../….. No specialist referral required.……………………..

3

Skin Tear

Burn

Dietician...../…../.… Vascular Surgeon …../…../….

Other

Full pain assessment completed and appropriate actions taken Wound care-plan discussed/agreed with the patient If pressure ulcer, Waterlow risk assessment, SSKIN and check list fully completed and reviewed If No to any of the above, reason for non-completion: Is it necessary to raise a safeguarding concern?

Yes Yes Yes

No No No

Yes

No

N/A Verbal Written

Lower limb un-healed wounds require full assessment with Doppler measurements at 4 weeks completed? Yes/No

Please sign and date every dressing change. Reassess wound as needed using clinical judgement and record any changes. Wound dimensions need to be measured at least weekly. Ensure that a separate form used for each wound

4

Dressing Change Date and Time DD/MM/YY 0.00hrs Wound Dimension (cm) Maximum length Maximum width Maximum depth Undermining Visible Tendon/bone Yes/No Wound Bed (approx % cover) Necrotic – black Sloughy – yellow green Granulating – red Epithelialising – pink Wound edges Healthy H Rolled RO Raised R Undermined U Suture/clips Yes/No/removal date Exudate levels High H Moderate M Low L Type and colour Surrounding Skin Macerated M Oedematous O Excoriated E Fragile F Dry D Eczema X Healthy H Wound Pain scale 1 -10 (10 high) Continuous C Dressing D None N Clinical signs of infection present: i.e. 2 or more of the following present; pus, odour, deterioration, spreading erythema, heat, increased pain, increased exudate, abscess, friable tissue. Infection present? yes/no If yes, swab taken (date) Antibiotic therapy commenced (date) Treatment Objectives Patient comfort PC Absorption A Infection Control ICDebridement D Odour Control OCPromote granulation G Promote epithelialisation E Cleansing Solution Dressing Choice (if Topical Negative Therapy in use, document details here) Skin Emollient/Cream Frequency of dressing change (Number of days) Date of review or healed Signed Print name Designation

5

TIME – Principles of Improved Wound Healing (Wound Bed Preparation) The concept of wound bed preparation has gained international recognition as a framework that can provide a structured approach to wound management -

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By definition wound bed preparation is ‘the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. - The concept focuses the clinician on optimizing conditions at the wound bed so as to encourage normal endogenous healing. It is an approach that should be considered for all wounds that are not progressing to normal wound healing Wound bed preparation care cycle -

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The care cycle starts with the patient and their environment of care. Individual patient concerns need to be addressed as well as quality of life issues in order to achieve a successful care programme. Patients need to understand the underlying cause of their wound and the rationale for treatments. Assessment and treatment of the underlying condition is essential as the type of wound bed preparation implemented may vary with wound type. For example, sharp debridement is common in the management of patients with diabetic foot ulceration, while compression therapy is the recommended treatment for patients with venous leg ulcers The cycle moves from patient assessment and diagnosis to assessing and treating the wound using the TIME framework.

The importance of assessment in terms of evaluating the effectiveness of the treatment is highlighted in the cycle. Those patients who have healed come out of the cycle into a ‘prevention programme’ and patients who have not progressed to healing or who have palliative wounds remain in the cycle and are reassessed, using TIME.

The TIME frame work -

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6

To assist with implementing the concept of wound bed preparation, the TIME acronym was developed in 2002 by a group of wound care experts, as a practical guide for use when managing patients with wounds The four main components of wound bed preparation: 1. T: Tissue management 2. I: Control of infection and inflammation 3. M: Moisture imbalance

4. E: Advancement of the epithelial edge of the wound. -

plan of care to remove these barriers and promote wound healing. If a wound fails to heal there is often a complex mix of local and host factors which will need to be assessed and treated.

The TIME framework is a useful practical tool based on identifying the barriers to healing and implementing a

TIME- Principles of Wound Bed Preparation Clinical observations

Proposed pathophysiology

WBP clinical actions

Effect of WEP actions

Clinical outcomes

Tissue non-viable or deficient

Defective matrix and cell debris impair healing

Restoration of wound base and functional extra cellular matrix proteins

Viable wound base

Infection or inflammation

High bacterial counts prolonged inflammation increase inflammatory cytokine increase Protease activity increase Growth factor activity

Debridement (Episodic or continuous) - autolytic, sharp surgical enzymatic, mechanical or biological Biological agents Remove infected foci Topical/systemic antimicrobials Antiinflammatory Protease inhibition

Bacterial balance and reduced inflammation

Moisture imbalance

Desiccation slows epithelial cell migration. Excessive fluid causes maceration of wound margin

Apply moisture balancing Compression, negative of removing fluid

Edge of wound: non advancing or undermined

Non-migrating keratinocytes Non-responsive wound cells and abnormalities in extracellular matrix or abnormal protease activity

Re-assess cause or consider corrective therapies • Debridement •Skin grafts • Biological agents Adjunctive therapies

Low bacterial counts or controlled inflammation decrease inflammatory cytokines decrease Protease activity increase Growth factor activity Restored epithelial cell migration, desiccation avoided oedema. excessive fluid controlled maceration avoided Migrating keratinocytes and responsive wound cells. Restoration of appropriate protease profile

7

Moisture balance

Advancing edge of wound

1. T = Tissue - The specific characteristics of the tissue within a wound bed play a very important role in the wound healing continuum. - Accurate description of this tissue is an important feature of wound assessment. - Where tissue is non-viable or deficient, wound healing is delayed. It also provides a focus for infection, prolongs the inflammatory response, mechanically obstructs contraction and impedes re-epithelialisation - Necrosis, eschar, and slough are terms that describe non-viable tissue - For epidermal cells to migrate across a wound surface a well-built extracellular matrix is required. Therefore, early interventions to remove devitalised tissue are an essential part of wound management. - Necrosis or eschar on a wound is usually identified through its black/dark grey appearance and, when dried out, is tough and leathery to touch. - Wound eschar is full thickness, dry, devitalised tissue that has arisen through prolonged local ischemia. It is derived from granulation tissue after the death of fibroblasts and endothelial cells and may also contain inflammatory cells which increases the risk of chronic inflammation of the wound and delays extracellular matrix formation. - Necrotic tissue acts as a physical barrier to epidermal cell migration, and hydration at the wound interface is significantly reduced. - Slough is adherent fibrous material derived from proteins, fibrin and

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fibrinogen. It is usually creamy yellow in appearance and can be found dehydrated and adhered to the wound bed or loose and stringy when associated with increased wound moisture. The presence of devitalised tissue in a wound is often a challenge to health care professionals. It is difficult to accurately assess the depth of a wound that is covered or filled with necrotic or sloughy tissue and, until removed, the true extent of the wound may not be realised. In the majority of clinical cases there is a need to remove the devitalised tissue through a process of debridement, however, it is important to assess the blood flow to the affected area first, particularly if the wound is on the lower leg or foot. In cases where the limb requires revascularisation, it may not be appropriate to undertake tissue debridement until the viability of the limb is determined

Debridement -

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- Hydro surgery - Ultrasonic methods - Surgical debridement is traditionally perceived to represent the gold standard form. however, no form of debridement has been proven superior over another 1. Surgical (or sharp) debridement - Surgical and sharp debridement are the fastest methods of removing devitalized tissue and have the benefit of converting a non-healing chronic wound to that of an acute wound within a chronic wound environment - Surgical debridement is normally performed where there is a large extent of devitalized tissue present and where there are significant infection risks. It is an invasive method using either a curette or scalpel, which involves the removal of callus, non-viable tissue, biofilm, slough and/or foreign bodies as well as debridement of the wound edges and base down to healthy bleeding tissue - Sharp debridement is more conservative, but it still requires the skills of an experienced practitioner. - Clinical competencies such as knowledge of anatomy, identification of viable or non-viable tissue, ability and resources to manage complications

Debridement is the process of removing devitalized tissue and/or foreign material from a wound and it may occur naturally. However, in some cases the patient may have an underlying pathology which affects the ability of the body to naturally debride the wound. The purpose of wound bed debridement is - Removal of necrotic tissue - Reduction of pressure - Inspection of underlying tissue - Elimination of dead space harboring bacteria - Drainage of pus - Optimization for topical preparations in an attempt to stimulate healing In a chronic wound, debridement is often required more than once as the healing process can stop or slow down allowing further devitalized tissue to develop

Methods of debridement -

Surgical (or sharp) Autolytic Chemical Larval Mechanical

9

such as bleeding and the skills to obtain patient consent are all essential before undertaking this procedure. Caution should be exercised in patients on anticoagulants or who are immunosuppressed

4. Larval therapy - Larval therapy is a quick, efficient method of removing slough and debris from a wound, however, not all patients or staff find this debridement method socially acceptable. - Larval therapy is a form of atraumatic selective removal of moist slough using larvae from the green bottle fly (Lucilia sericata or Lucilia cuprina); they can ingest pathogenic organisms but cannot remove callus - Sterile larvae secrete powerful enzymes to break down devitalised tissue without destroying healthy granulation tissue 5. Mechanical debridement - Mechanical methods of debridement such as irrigation and wet to dry dressings are rarely used as they can cause increased pain and can damage newly formed granulation tissue 6. Hydrosurgery - Hydrosurgery consists of wound lavage through a pressurised hand piece or whirlpool. It is relatively painless and has been shown to reduce bioburden 7. Ultrasonic method - Low-frequency, low-dose ultrasonicassisted debridement can be undertaken with either contact or noncontact devices. - Contact devices work by cavitation and acoustic streaming, which directly agitates the wound bed. - Non-contact devices work in conjunction with atomised saline. They are relatively painless, but the equipment can be expensive and not often readily available.

2. Autolytic debridement - Autolytic debridement is a highly selective process involving macrophage and endogenous proteolytic enzymes which liquefy and separate necrotic tissue and eschar from healthy tissue - A method using moisturisation to allow degradation by phagocytic cells, softening of necrotic tissue and liquefaction of slough. - Phagocytic activity is enhanced and increasing the moisture at the wound interface promotes tissue granulation. - It includes moist dressings such as hydrocolloid and alginate dressings, honey dressings, hydrogels and polyarylates - Wounds with high exudate output may not be suitable for this method 3. Chemical & Enzymatic debridement - Chemical debridement: the use of antiseptics such as silver, povidoneiodine, chlorhexidine, PHMB or octenidine can achieve debridement. Hydrogen peroxide or sodium hydrochloride have a limited role because of the toxic effects and pain experienced with their use - Enzymatic debridement (Subtype of Chemical debridement) is a less common method of debridement; however, it is effective in the removal of hard necrotic eschar where surgical debridement is not an option. Exogenous enzymes are applied to the wound bed where they combine with the endogenous enzymes in the wound to break down the devitalised tissue.

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Effect of Wound debridement

Periwound callusing obscures much of the underlying ulcer

The wound is now clear of all nonviable tissue

Periwound callusing contributes to incomplete wound contraction

The wound periphery now exhibits a firm connection between the epidermis and dermis

Large quantities of fibrous callusing and devitalized tissue are evident

Devitalized tissue has been removed down to the level of viable, bleeding tissue

Large wound exhibiting necrotic, nonviable tissue, foreign matter and bacteria

Aggressive debridement has cleared necrotic tissue and bacteria

Photos provided by Dr.Arti Masturzo, MD, CWS, ABPM/UHM

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Wound Care Guidelines for Different Tissue Types

Notes -

Depth: May be difficult to assess fully until necrosis has lifted Surrounding Skin: If wound exuding or skin is fragile, protect with no sting barrier film. Nutrition: Assessment must be carried out and appropriate referral made. Specialist Input: Sharp debridement must be carried out by a doctor or Tissue Viability Nurse only. Seek further advice for patients with diabetes or arterial problems.

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Notes -

Bandages: Tight or compression bandages must not be used for patients with diabetes or arterial problems unless under close supervision of Specialist team. Surrounding Skin: If wound is exuding or skin is fragile, protect with no sting barrier film. Nutrition: Assessment must be carried out and appropriate referral made. Specialist Input: Seek further advice for patients with diabetes or arterial problems.

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Notes -

Slow/static debridement: consider larvae therapy. Cavities: Consider Topical Negative Pressure therapy, refer to Tissue Viability Nurse for advice. Very High Exudate: consider above or wound drainage bags, refer to Tissue Viability Nurse for advice. Surrounding Skin: If wound exuding or skin fragile, protect with no sting barrier film. Nutrition: Assessment must be carried out and appropriate referral made. Specialist Input: Sharp debridement must be carried out by a doctor or Tissue Viability Nurse only. Seek further advice for patients with diabetes or arterial problems.

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Notes -

Bleeding: Use an alginate to act as a haemostat (Kaltostat®). Cavities: Consider Topical Negative Pressure therapy, refer to Tissue Viability Nurse for advice. Very High Exudate: Consider wound drainage bags, refer to Tissue Viability Nurse for advice. Surrounding Skin: If wound exuding or skin fragile, protect with no sting barrier film. Nutrition: Assessment must be carried out and appropriate referral made. Specialist Input: Seek further advice for patients with diabetes or arterial problems.

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Notes -

Protection: Of the wound site is essential for complete healing/ maturation. Surrounding Skin: If wound exuding or skin fragile protect with no sting barrier film. Nutrition: Assessment must be carried out and appropriate referral made. Fragile/Sensitive Skin: Silflex® can be considered as alternative dressing as it can remain on the wound for 7 days. Specialist Input: Seek further advice for patients with diabetes or arterial problems.

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Notes -

Surrounding Skin: If wound exuding or skin fragile, protect with no sting barrier film. Nutrition: Assessment must be carried out and appropriate referral made. Specialist Input: Seek further advice for patients with diabetes or arterial problems. Lower limb injury: Secure dressing with wool bandage and crepe bandage applied from toe to knee Tissue adhesive (Liquiband Optima not on FP10 or formulary): training/ competency is available for first line services

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2. I = Infection / Inflammation - Infection in a wound causes pain and discomfort for the patient, delayed wound healing, and can be life threatening. - Clinical infections as well as having serious consequences for the patient can add to the overall cost of care. - All wounds contain bacteria at levels ranging from contamination, through critical colonisation (also known as increased bacterial burden or occult infection), to infection. - The increased bacterial burden may be confined to the superficial wound bed or may be present in the deep compartment and surrounding tissue of the wound margins. - Several systemic and local factors increase the risk of infection. Local factors Large wound area Deep wound High degree of chronicity Anatomic location e.g., Anal region Presence of necrotic tissue High degree of contamination Reduced tissue perfusion

Checklist of factors associated with increased risk of wound infection Characteristics of the individual - Poorly controlled diabetes - Prior surgery, Radiation therapy or chemotherapy - Conditions associated with hypoxia and/or poor tissue perfusion (e.g., anemia, cardiac or respiratory disease, arterial or vascular disease, renal impairment, rheumatoid arthritis, shock) - Immune system disorders (e.g., acquired immune deficiency syndrome, malignancy) - Inappropriate antibiotic prophylaxis, particularly in acute wounding - Protein-energy malnutrition - Alcohol, smoking and drug abuse - Presence of significant lymphoedema, skin conditions, hematoma, seroma, abscess, fistula - A history of self-harm - A carrier or infected with a multi-drug resistant organism (i.e., ‘alert organism’) - Recent travel (i.e., abroad, between multiple care settings) - Level of mental capacity, knowledge and understanding (WUWHS, 2020a)

Systemic factors Vascular disease Oedema Malnutrition Diabetes mellitus/Rheumatoid arthritis Smoking/Alcoholism Previous surgery or radiotherapy Corticosteroid/Immuno suppression

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Characteristics of the wound Acute wounds Contaminated or dirty wounds

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Trauma with delayed treatment Pre- existing infection or sepsis Spillage from GIT

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Penetrating wounds over 4 hours

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Inappropriate hair removal Operative factors (e.g., long surgical procedure, hypothermia, blood transfusion)

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Chronic wound Degree of chronicity/duration of wound Large wound area

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Both wound types Foreign body (e.g., metal work, drains, sutures) Hematoma

Deep wound

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Necrotic wound tissue

Anatomically located near a site of potential contamination (e.g., perineum or sacrum)

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Impaired tissue perfusion

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Increased exudate or moisture

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Characteristics of the environment

Mechanism of wound infection

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Hospitalization (due to increased risk of exposure to antibiotic resistant organisms) Poor hand hygiene and aseptic technique Unhygienic environment (e.g., dust, unclean surfaces, mould/mildew in bathrooms) Inadequate management of moisture, exudate and edema Inadequate pressure off-loading Repeated trauma (e.g., inappropriate dressing removal technique)

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When a wound is infected, it contains replicating micro-organisms which elicit a host response and cause injury to the host. In an acute wound, infection is met by a rapid inflammatory response which is initiated by complement fixation and an innate immune response followed by the release of cytokines and growth factors. The inflammatory cascade produces vasodilation and a significant increase of blood flow to the injured area. This also facilitates the removal of microorganisms, foreign bodies, bacterial toxins and enzymes by phagocytic cells, complements, and antibodies.

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The coagulation cascade is activated isolating the site of infection in a gel matrix to protect the host. In a chronic wound, however, the continuous presence of virulent microorganisms leads to a continued inflammatory response which eventually contributes to host injury. There is persistent production of inflammatory mediators and steady migration of neutrophils which release cytolytic enzymes and oxygen-free radicals. There is localized thrombosis and the release of vasoconstricting metabolites which can lead to tissue hypoxia, bringing further bacterial proliferation and tissue destruction. The presence of bacteria in a chronic wound does not necessarily indicate that infection has occurred or that it will lead to impaired wound healing Micro-organisms are present in all chronic wounds and low levels of certain bacteria can facilitate wound healing as they produce enzymes such as hyaluronidase which contributes to wound debridement and stimulates neutrophils to release proteases.

Causes of (AMR) 1) Genetic Cause of AMR: - The primary function of microorganisms is to reproduce and survive. Therefore, microbes continually adapt to their environments to ensure their survival. - If something stops their ability to grow, such as an antimicrobial, genetic changes can occur that enable the microbe to survive. a. Mutational resistance: - It is caused by a genetic change in the organism that affects the activity of the drug, resulting in preserved cell survival in the presence of the antimicrobial. b. Horizontal Gene Transfer (HGT): - It is caused by the acquisition of foreign DNA material. It is one of the most important drivers of bacterial evolution and it is frequently responsible for the development of AMR Genetic modifications can lead to the following AMR modes of action in bacteria: A. Drug modification or destruction: - Bacteria either inactivate or destroy the antibiotic molecule itself. B. Efflux mechanisms: bacteria have mechanisms to remove antibiotics that have entered the cell. C. Permeability barrier: bacteria block the entry of antibiotics into the cell. D. Altered target site: bacteria modify the antibiotic target site so that the antibiotic is no longer able to have an effect 2) Human Causes of AMR: - Inappropriate or overuse of antibiotics is one of the biggest causes of antibiotic resistance in medicine and agriculture.

The Anti-Microbial Resistance: -

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Antimicrobials are a group of agents that either kill or inhibit the growth and division of microorganisms. They include antibiotics (which act on specific cellular target sites), antiseptics, disinfectants and other agents, such as a antiviral, antifungal, antibacterial and antiparasitic medicines (which act on multiple cellular target sites). Antimicrobial resistance (AMR) describes when micro-organisms evolve over time and no longer respond to any antimicrobial therapy.

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Inadequate infection diagnostics with incomplete or imperfect information encourages the prescription of antimicrobials ‘just-in-case’ or the prescription of a broad-spectrum antimicrobial when a specific antibiotic might be better. Critically ill patients in hospital are more susceptible to infections and, thus, often require antimicrobials. The extensive use of antimicrobials and close contact among sick patients creates a fertile environment for the spread of antimicrobial-resistant germs (e.g., methicillin-resistant Staphylococcus aureus [MRSA]). Poor hygiene, sanitation, and lack of access to clean water

a) Debride the wound of necrotic tissue, debris, foreign bodies, wound dressing remnants and slough b) Cleanse the wound at each dressing change c) Use aseptic technique for acute wounds and a clean technique for chronic ulcer - Optimize management of comorbidities (e.g., diabetes, tissue perfusion/oxygenation) - Optimize nutritional status and hydration - If the patient is at considerable risk, decontamination measures should be considered (e.g., cleaning and waste disposal), and in some cases isolation may be considered - Patient capacity for self-care should be established; in the home setting, education about hygiene may be needed (e.g., how best to apply creams without increasing infection risk, suitable bathing products, how best to dry their skin with a clean towel) - Consider antimicrobial treatment in some instances, such as suspected diabetic foot infections and suspected surgical site infections 2. Environment - Clean/disinfect surfaces before use - Reduce clutter (e.g., ensuring appropriate storage spaces for equipment and dressings) - Use appropriate waste disposal facilities for unused antimicrobial therapy and dressings and materials that may harbor antimicrobial resistant bacteria - Provide adequate lighting - In the patient’s home: Consider the impact of any pets in the home environment (i.e., keeping them away from the wound and ensuring general hygiene is maintained

Infection prevention -

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Infection prevention is an important element in wound care. The foundation of infection prevention in wound care should reflect a back-tobasics approach. The components of the back-to-basics approach include: 1. Hand hygiene/decontamination 2. Use of personal protective equipment (PPE) 3. Good waste management 4. Comprehensive documentation 5. Management of the patient’s environmental

Summary of infection prevention and AMS practice considerations 1. Patient and wound - Avoid any break in the skin and preserve overall skin integrity (i.e., keep skin clean, dry and well hydrated) according to local policy and international guidance - Implement wound bed preparation to reduce wound or skin microbial load:

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3. Healthcare professionals and carers - Hand hygiene - Adhere to uniform policy, and consider that this may not provide full and upto-date information; for example, the following should be avoided: - False nails/gel nails (dirt behind long nails is an infection risk) - Jewelry (apart from a wedding band and stud earrings) - False eyelashes - Wearing hair down (touching or below the collar) - Fitness tracking watches or devices - Training for new staff: ensure that all staff have up-to-date with local protocols - Staff with skin conditions: assess on an individual basis if they should be working or require extra PPE - Staff illness: staff should be encouraged to stay at home if there is an infection risk. 4. Protocol - Prevent cross-infection by implementing universal precautions and aseptic technique - Work to reduce/manage exposure of dressings/ bandages to urine, faeces or other contaminants (use barrier cream where necessary) - Avoid ‘double dipping’ in larger pots of creams and ointments - Improve documentation of infection - Routine review of antibiotics and antimicrobials - Store equipment and supplies appropriately - Regularly review local policies and procedures - Remember that AMS is everybody’s responsibility throughout the patient journey.

The Infection Continuum -

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The infection continuum describes the relationship between increasing microbial virulence and the clinical response invoked within the patient. The continuum encourages vigilance to encourage early identification to trigger when intervention is required.

Stages of the infection continuum: Contamination: -

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Wound contamination is the presence of non-proliferating micro-organisms within a wound at a level that does not evoke a host response. All open wounds are contaminated with endogenous and exogenous microbial sources caused by environmental exposure and the patient’s natural skin flora. Unless the host defenses are compromised, the host immune system will respond swiftly to destroy bacteria. Vigilance is required, but antimicrobials are not indicated at this stage.

Colonisation: -

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Colonisation refers to the presence of micro-organisms in the wound that have undergone some proliferation, but there is no host reaction. Microbial growth occurs, but at a level that is non-critical and wound healing is not delayed or impeded

Local wound infection: -

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Wound infections are caused by the multiplication of micro-organisms in the wound of a susceptible patient at a rate that the host defenses are unable to overcome the micro-organism in the wound.

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Intervention is generally required to assist the host defenses in destroying invading micro- organisms. - Microorganisms can enter into wounds in a number of ways: a) Direct contact: transfer from surgical equipment or the hands. b) Airborne dispersal: surrounding air contaminated with micro-organisms that deposit onto the wound. c) Self-contamination: physical migration of the patient’s own endogenous flora, which is present on the skin, mucous membranes, or gastrointestinal tract.

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Spreading and systemic infection: -

Biofilm: -

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It is now widely accepted that biofilm is present in 70–100% of chronic wounds. However, identification and management of biofilm remains a complex task. A biofilm is an aggregated community of slowgrowing bacteria that are tolerant to host defenses and to antimicrobial treatment Their altered metabolism, umbrellalike protective matrix and altered lowoxygen microenvironment increases their tolerance to antimicrobials. Biofilms are often polymicrobial, involving clusters of different types of bacterial cells growing at different rates, which are challenging to treat. Biofilms are not visible to the naked eye and can be difficult to confirm unless a biopsy is taken and visualized by microscopy, therefore, there are subtle clinical indicators of biofilm that are relied upon for diagnosis.

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Spreading infection describes the invasion of the surrounding tissue by micro- organisms that have spread from the wound to deep tissue, muscle, fascia, organs, or body cavities. Micro-organisms spread via the vascular or lymphatic system and can spread to the whole body. If systemic or spreading infection is present, antibiotic therapy must be started immediately while awaiting culture results. A sample/wound swab must be taken to determine the bacteria present and guide appropriate antibiotic use. The therapy should be reviewed and revised based on clinical response and microbiological culture/susceptibility results.

Red flag: acute deterioration or sepsis: -

Clinical indicator of Biofilms -

Recurrence of delayed healing on cessation of antibiotic/ antimicrobial treatment Increased exudate/ moisture Low-level chronic inflammation Low-level erythema Poor granulation/ friable hypergranulation Wound breakdown and enlargement

Failure to respond to antibiotic/ antimicrobial treatment

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Sepsis is a rare, but potentially fatal, condition. Recognizing and treating infection early, before sepsis develops, is vital. If the patient looks ill, has triggered the National Early Warning Score (pulse, blood pressure, respiratory rate, oxygen levels, temperature and conscious level), or there are signs of infection – then the patient should be screened for sepsis.

Symptoms of sepsis 1) Seek medical help urgently if you (or another adult) develop any of these signs: 2) Slurred speech or confusion 3) Extreme shivering or muscle pain 4) Passing no urine (in a day) 5) Severe breathlessness 6) It feels like you’re going to die 7) Skin mottled or discolored

Diagnosis: -

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Diagnosis using gold standard methods should be mandatory prior to initiation of antibiotics however, approaches to infection diagnosis depend on clinical expertise and locally available methods. These may include: bedside assessment of the clinical signs and symptoms of each stage of the infection continuum, surface wound swabbing and wound biopsy. The classic signs of infection in acute wounds include: Pain Erythema

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- Edema - Purulent discharge - Increased heat. For chronic wounds it has been suggested that other signs should be added: - Delayed healing - Increased exudates - Bright red discoloration of granulation tissue - Friable and exuberant tissue - New areas of slough - Undermining & Malodour and wound breakdown

Signs and symptoms associated with stages of the wound infection continuum Contamination

Colonisation

Local infection Covert

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All wounds  may acquire microorganisms. If suitable nutritive and physical conditions are not available for each microbial species, or they are not able to successfully evade host defences, they will not multiply or persist their presence is therefore only transient and wound healing is not delayed

Microbial species successfully grow and divide, but do not cause damage to the host or initiate wound infection

Spreading infection Overt

(subtle) signs of local infection:

(classic) signs of  local infection:

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Systemic infection

Hypergranulatio n (excessive vascular’ tissue) Bleeding, friable granulation tissue Epithelial bridging and pocketing in granulation tissue Wound breakdown and enlargement Delayed wound healing beyond expectations New or increasing pain Increasin g malodor

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Erythema Local warmt h Swelling Purulent discharg e Delayed wound healing beyond expectation s New or increasin g pain Increasin g malodor

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Role of swabbing and sampling: - Wound swabbing is a simple, convenient, widely available and noninvasive procedure, but it is not a tool that can be used to diagnose in isolation. - Swabbing guides antibiotic selection against the organisms causing the clinical signs of infection, it does not determine whether infection is present or not. - Routine swabbing in the absence of clinical indicators of infection is neither helpful nor cost effective. - Questions to consider when deciding whether to swab 1) Is the current therapy appropriate based on the last results?

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Extending in duration +/erythema Lymphangitis Crepitus Wound breakdown / dehiscence with or without satellite lesions Malaise/ lethargy or non- specific general deterioration Loss of appetit e Inflammation , swelling of lymph glands

2) Has the therapy had time to work (2–3 days)? 3) Is there deterioration? If so, is this deterioration deep (i.e., is a tissue sample required at theatre level)? 4) Are there signs of spreading or systemic infection? A swab will always identify the presence of micro-organisms. The presence of an organism in an infected wound does not necessarily mean that it has caused the infection, and in practice it is not possible to differentiate between pathogenic and non-pathogenic organisms. Bacterial infection with multiple species produces a synergistic effect, leading to increased production of

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Sever e sepsis Septi c shock Organ failur e Death

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virulence factors and greater delays in healing, suggestive of biofilm. The most common causative organisms associated with wound infections include Staphylococcus aureus/MRSA, Streptococcus pyogenes, Enterococci and Pseudomonas aeruginosa.

alternatives to antibiotics, such as topical antiseptics. - There is strong and growing evidence that antiseptics can be useful agents in attempts to reduce AMR but are underused, particularly in the fields of wound care and surgical site management. - Antiseptics are non-selective agents that are applied topically to stop growth or kill micro- organisms. - They are relatively non-toxic and are not significantly absorbed through the skin, as such development of resistance to antiseptics is uncommon. - Topical antiseptics are available in dressings, ointments, powders and cleansing solutions (e.g., silver, honey, iodine, octenidine dihydrochloride, polyhexamethylene biguanide [PHMB]). Dressings that have a physical mode of action: - Cleansing lotions that contain surfactants loosen and remove surface debris and the associated microbial load. - A surfactant reduces the surface tension holding debris (dried exudate, loose and devitalized mucous membrane) to the wound bed. - Products that offer an alternative approach to the management of increasing bacterial load in chronic wounds, such as dressings with a physical mode of action are effective in wound bioburden management as there is no risk of bacteria developing resistance. - Dressings coated in a fatty acid derivative irreversibly bind to bacteria and sequester their activity. As there is no risk of bacteria developing resistance, these dressings may be used prophylactically, but are best used on

Antibiotics:Antimicrobial treatment selection -

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Antibiotic misuse in wound care occurs because of diagnostic uncertainty concerning the presence of a bacterial infection, lack of knowledge of lower limb infections (e.g., bilateral lower limb cellulitis, also known as red leg, can be often mistaken for infection), clinicians’ fear of achieving unfavorable patient outcomes and patient demand. Systemic antibiotics should be reserved for the treatment of serious bacterial infections in high-risk patients when other treatment options are ineffective or not available. The antibiotic selected should be specifically focused to the microorganism and administered for the shortest duration Possible. Also, switching from intravenous to oral therapy as soon as patients are clinically stable can reduce the length of hospitalization, thus reducing the risk of hospital-acquired complications, and reducing associated costs. The only topical antibiotics recommended for wound infections are mupirocin, fusidic acid and metronidazole.

Antiseptics: -

In wound care, antibiotic-resistant bacteria present a serious issue, necessitating the consideration of

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unclean, colonized or infected exuding wounds. Right time to initiate antimicrobial treatment: - The presence of clinical signs and symptoms of infection and indicators of biofilm, and local protocol determine when antimicrobial treatment is initiated. - Antimicrobial agents should not be routinely used as a precautionary measure if the wound is not clinically infected. - However, there are some instances where antimicrobial treatment is indicated if infection is suspected: 1) Suspected diabetic foot infections: - There are no convincing data to support the concept that prescribing antibiotic therapy for clinically noninfected ulcers either accelerates healing or reduces the risk of developing clinically apparent infection. - NICE recommends to start antibiotic treatment for people with suspected diabetic foot infection as soon as possible. Take samples from the base of the debrided wound for microbiological testing before, or as close as possible to, the start of antibiotic treatment. - If a swab at the base of the wound cannot be obtained, take a deep swab because it may provide useful information on the choice of antibiotic treatment.

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2) Surgical site infection: -

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Prophylactic antibiotic therapy is usually given as a single dose at induction of anaesthesia, but should not be continued after surgery NICE recommends that when a surgical site infection is suspected due to the presence of cellulitis, either by a

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new infection or an infection caused by treatment failure, the patient should be given an antibiotic that covers the likely causative organisms and considers the results of microbiological tests. The Best Practice Statement Postoperative wound care reducing the risk of surgical site infection provides guidance on strategies that promote AMS.

Wound infection assessment in specific wound types Type of wound

Specific considerations

Surgical site infection

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Pressure ulcer/injury

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Diabetic foot ulcer

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Chronic leg ulcers

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Skin tears

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Daily visual wound assessment (where possible depending on the type of wound dressing applied following surgery) and vital sign assessment Early indicators of wound infection: Increased wound-edge distance (lack of approximation) Increased wound exudate Increased heart rate Increased morning tympanic temperature Increasing pain Wound edge colour (e.g. redness) and induration are not reliable indicators of wound infection and may present differently depending on the individual’s skin tone Associated with spreading infection (e.g. cellulitis) and increased markers for infection Full thickness pressure ulcers/injuries (i.e. Category/Stage 3 or 4 pressure ulcers/injuries) are more likely to exhibit any signs of infection, but particularly erythema and purulent exudate Observe for indirect indicators of systemic infection (e.g. anorexia, delirium and/or confusion) Sepsis is uncommonly reported Probing to the bone with a sterile metal probe or instrument to diagnose diabetic foot osteomyelitis is inexpensive, accessible and relatively safe Probing to the bone combined with plain X-rays and biomarkers of infection (e.g. ESR, CRP and/or PCT) can be used to diagnose osteomyelitis in the diabetic foot An increase in temperature in one area of the diabetic foot identified using infrared or digital thermometry (if accessible) combined with photographic assessment may be of value in the initial assessment of infection when performed via telemedicine Wound observations that are independent predictors of infection: Ulcer area of 10cm2 or larger Presence of wound bed slough Heavy wound exudate (however, consider exudate level in the context of whether leg volume reduction through compression has been achieved) Depression, chronic pulmonary disease and anticoagulant use are predictors of wound infection Distinguish trauma-related inflammation from infection Early indicators of infection include:  Increased wound-edge distance (lack of approximation)  Increased wound exudate, Increasing pain  Skin flap failure Mechanism of injury should be considered (tetanus vaccination/booster may be required)

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Right duration of antimicrobial treatment: If antibiotics are prescribed, the course should be completed to avoid infection reoccurrence and to reduce the risk of the bacteria becoming resistant to the antibiotics. If the patient does not intend to finish the course, they should be advised to contact the prescriber. If there is no response or improvement after the designated duration of antimicrobial treatment, management needs to be reviewed as per local protocol. The ‘two-week’ challenge guides the appropriate duration of antimicrobial treatment and reassessment. Appropriate duration of antimicrobial treatment is an area of debate, with longer duration being associated with a heightened risk of inducing microbial resistance. The use of a highly effective antimicrobial is required for shorter duration treatments to kill bacteria, thereby minimizing the risk of inducing microbial resistance. Antimicrobial dressings are recommended to be used for a minimum of 2 weeks’ duration. After 2 weeks, re-evaluate and either: 1. Discontinue if signs and symptoms of infection have resolved 2. Continue with the antimicrobial if the wound is progressing but there are still signs and symptoms 3. Consider an alternative antimicrobial if there is no improvement and refer to a wound care specialist. A wound that does not progress and remains chronic could be indicative of the presence of biofilm. Antimicrobial failure and recurrence of delayed healing on cessation of antimicrobial

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treatment are well-established clinical indicators of the presence of biofilm. If the clinical indicators of biofilm are present, this may indicate a different management approach is required, including: 1. Debridement to physically disrupt and expose the micro-organisms to make them vulnerable to the effects of topical antiseptics and systemic antibiotics. 2. Cleansing to remove any residual debris and antimicrobial intervention against exposed bacteria and residual biofilm. Use of an antimicrobial with proven effect against mature biofilms in clinical practice or a dressing with a physical mode of action.

Examples of local indicators of improvement/deterioration of chronic wounds and may indicate infection Parameter Change that may indicate: Improvement Deterioration Wound bed  Increased amount of granulation tissue  Increased amount of slough/necrotic  Decreased amount of slough/ necrotic tissue tissue  Decreased amount  Reduction in wound area/volume of granulation tissue  Granulation tissue is friable  Increase in wound area/volume Exudate  Levels usually decrease as the wound  Increased level heals  Changed from clear to discoloured  Changed to clear if previously cloudy  Change in consistency, e.g. thinner to thicker Periwound  Reduction, if present, of:  Development, or increase in extent, skin  Maceration/excoriation of:  Erythema  Maceration/excoriation  Swelling  Erythema  Swelling Odour  Less noticeable or resolved if  Development, change previously an issue in or worsening of unpleasant odour Wound Reduced level or frequency  Development, change in nature related and/ or increase in pain level of pain N.B. Changes in wound area/volume may not be noticeable from one dressing change to the next, and a wound may increase in size when necrotic tissue and slough are removed. Taking photographs and measuring the wound helps to identify if the wound is improving. Patients with a diabetic foot ulcer and neuropathy may not experience pain; a patient with sudden onset of pain should be referred urgently

30

Antibacterial Guidelines

31

Wound Care Guidelines for Infected Wound

Notes -

Clinical signs of infection: Inflammation, erythema (redness), increased pain, odour, pus, heat, pyrexia, friable (bleeds easily). Surrounding Skin: If wound exuding or skin fragile, protect with no sting barrier film. Nutrition: Assessment must be carried out and appropriate referral made. Specialist Input: Seek further advice for patients with diabetes or arterial problems

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To Summary Wound Infection Management Assess the patient and thier comorbidities, wound(s), skin and enviroment to identify factors that may impact on infection. Comprehensive assessment and reviews will guide if changes to the management plan are required No wound present Infection risk factors present Follow strategies to reduce risk of infection and wound development

Wound present No infection risk factors No antimicobial treatment necessary Follow strategies to reduce risk of infection and promote wound healing

Wound present Infection risk factors present Is the wound progressing, non healing or deteriorating?

Progressing wound Antimicrobial treatment not necessary Follow strategies to reduce risk of infection and promote wound healing

Non healing wound (may be indicative of biofilm) Debride and cleanse Consider a dressing with a physical mode of action Strategies to reduce risk of infection , follow and promote wound healing Reassess at regular intervals are per local protocol and following the two week challenge principles

Deteriorating wound Debride and cleanse Use an antimicrobial topical agent or a dressing with a physical mode of action as per local protocol Consider potential for spreading or systemic infection and whether systemic antibiotics are required and whether a wound swab is appropriate Reassess at regular intervals as per local protocol and following the two week challenge principles

Local wound infection

Systemic or spreading wound infection

Topical antimicrobial agent Implement infection management Follow strategies to reduce risk of infection and promote wound healing Reassess at regular intervals as per local protocol and following the two week challenge principles

IV or oral antibiotics Refer to an appropriate clinical specialist Take a wound swab Topical antimicrobial agent Follow strategies to reduce risk of infection and promote wound healing

3. M = Moisture -

-

-

-

Creating a moisture balance at the wound interface is essential if wound healing is to be achieved. Exudate is produced as part of the body’s response to tissue damage and the amount of exudate produced is dependent upon the pressure gradient within the tissues A wound which progresses through the normal wound healing cycle produces enough moisture to promote cell proliferation and supports the removal of devitalized tissue through autolysis. If, however, the wound becomes inflamed and/or stuck in the inflammatory phase of healing, exudate production increases as the blood vessels dilate.

-

-

-

33

Evidence suggests that there are significant differences between acute and chronic wound fluid Acute wound fluid supports the stimulation of fibroblasts and the production of endothelial cells as it is rich in leukocytes and essential nutrients. Chronic wound fluid, however, has been found to contain high levels of proteases which have an adverse effect on wound healing by slowing down or blocking cell proliferation in particular keratinocytes, fibroblasts If a wound produces excessive amounts of exudate the wound bed becomes saturated and moisture leaks out onto the peri-wound skin causing maceration and

-

-

excoriation. This in turn could lead to an increased risk of infection. Goal in this assessment is to 1. Avoid Maceration 2. Reduction in excessive fluid, 3. Reduce oedema, 4. Avoid Desiccation., 5. Restore epithelial cell migration

-

Exudate assessment: Assessment of the exudate is an important part of wound management. The type, amount and viscosity of the exudate should be recorded and

-

dressings selected based on the exudate’s characteristics. If a wound is too dry, rehydration should be the principle of management, unless contraindicated as in the case of ischemic disease. Occlusive dressing products promote a moist environment at the wound interface. As wounds heal, the level of exudate gradually decreases. The management of excess exudate in chronic wounds, however, presents a challenge to many health care professionals.

Exudate types

Components of exudate Serous

Serous

Clear and watery. Bacteria may be present

Fibrinous

Cloudy. Contains fibrin protein strands

Purulent

Milky. Contains infective bacteria and inflammatory cells

Haemopurulent

As above but dermal capillary damage leads to the presence of red cells

Hemorrhagic

Red blood cells are a major component of the exudate

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Management and Dressing selection Color

Exudate

Aim and dressing selection

Pink

Nil

Red unbroken

Low

Red

Low

Red

High

Yellow

Low

Yellow

High

Black

Low

Green

High

Maintain moist environment, protect and insulate. Foams, thin hydrocolloids, thin hydroactives, film dressing and simple nonadherent dressing such as the modern tulles will provide the necessary cover Prevent skin breakdown. Thin hydrocolloids or film dressing provide protection Maintain moist environment and promote granulation and epithelization. Foams hydrocolloids, sheet hydrogels and film dressings will maintain a moist environment.it is possible to use a combination of amorphous hydrogels with a foam cavity dressing in deeper wounds Maintain moist environment, absorb exudate and promote granulation and epithelization. Foams, alginates and hydroactive dressings help control exudate. Hydrocolloids for deeper areas Remove slough, absorb exudate and maintain moist environment. Hydrogels in particular will rehydrate the slough and hydrocolloids will also aid in autolysis Remove slough and absorb exudate. Hydrocolloid as paste or powder for deeper wounds. Alginates will aid in removal of slough and absorb exudate Rehydrate and loosen eschar. Surgical debridement is the most effective method of necrotic material removal. Dressing can enhance autolytic debridement of the eschar. Amorphous hydrogels, hydrocolloid sheet Absorb infected exudate. hypertonic saline, silver, cadexomer iodine, interactive wet dressing, capillary wicking dressings

First-line interactive/bioactive dressings: - Interactive/bioactive dressings alter the wound environment and interact with the wound surface to optimize healing. - The ability to provide a moist, conducive environment for improved healing when compared with traditional passive dressings has meant that new dressing technologies are a better alternative. - Interactive dressings use the environment provided by the body to encourage normal healing and stimulate the healing cascade

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Dressing

Brand names

Indications

Semi-permeable films

Aqua protect film,bioclusive ,Cutifilm ,Hydrofilm , Opsite (Flexigred,Flexifix, Post-Op)

Non-absorbent; superficial burns, grazes, closed surgical incisions, small skin tears and IV sites; secondary dressing

Foams

Allevyn (adherent, non-adherent, wound cavity dressing) Cavi-care, Curafoam , hydrosorb , Lyofoam (flat, extra C, T, A) permafoam , Tegafoam ,Truefoam

Moderate to heavily exudating, superficial and cavity wound, venous ulcers (with compression) pretibial lacerations, infected ulcers, skin tears, pressure ulcers, skin grafts or donor site, pilonidal sinuses

Alginates

Algisite M,Algoderm, Comfeel Need exudate to function. Heavily exudating leg seasorb Kaltostat, Melgisorb,sorbsan ulcers, pressure ulcers and dehisced abdominal wounds

Hydrocolloids

Comfeel (ulcer dressing, transparent, contour dressing) combiDERM, DuoDERM (extra thin, CGF, paste) Hydrocoll ,RepliCare, Tegasorb

Light to moderately exudating wound that would benefit from autolytic debridement. Leg ulcers, pressure ulcers, burns and donor sites. Thin sheets are useful over suture lines and IV sites

Hydrogels

Aquaclear , purilon Gel (amorphous , curafil (amorphous) ,Curagel (sheet), DuoDERM Gel (amorphous unpreserved ), Hypergel (hypertonic saline , amorphous ) , intrasite conformable (gauze impregnated ) Intrasite Gel (amorphous unpreserved), Nu-gel , second skin , SoloSite Gel (amorphous preserved) Solugel (amorphous preserved and unpreserved) ,Sterigel (amorphous)

Absorbency is limited; best for minimally exudating or dehydrated wounds such as minor burns, grazes, laceration, donor site and pressure ulcers. Indications for the thicker viscosity products include protection of exposed tendon and/or bone from dehydrating and rehydrating eschar prior to debridement. The thinner viscosity products are useful for soothing burns and acute lesions such as chicken pox

Hydroactive

Allevyn Thin , BIatain , Cutinova Hydro , PloyMem, Tielle

Waterproof, expandable, non-residual and semipermeable. Highly exudating surface and cavity wounds including leg ulcers, pressure wounds and minor burns. Useful over joints as they expand/contract without causing constriction. Not indicated for dry or lightly exudating wounds

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Second-line advanced interactive/bioactive dressings: Dressing

Brand names

Indications

Cadexomer

Iodosorb (Sheet, powder, paste)

Capillary wicking

Vacutex

Honey

Medihoney, B-Naturals, LMesitran .Medihoney is a blend that includes honey from the Leptospermum species of plants. Medihoney and Medihoney wounds Gels do not contain preservatives. B-Natural’s medicated honey is obtained from the Eucalyptus marginata and Santalum spicatum species of plants and does not contain preservatives LMesitran contains 48% honey , aloe , calendula, zinc oxide , medilan and vitamins A, C,and E Aquacel, Aquacel Ag

Venous leg ulcers, foot ulcers and diabetic foot ulcers Contraindicated in patients sensitive to iodine products or with any thyroid pathology Heavily exudating and infected wounds. Contraindicated in low exudating wounds within close proximity to blood vessels May be useful in management of sloughy and septic wounds

Hydrofibre

Hypertonic saline Interactive wet Silicone

Curasalt, Hypergel, Mesalt

Silver

Acticoat, Acticoat absorbent (calcium alginate) Actisorb 220 (charcoal impregnated) Aquacel Ag (hydrofibre) Atrauman Ag ( wound contact tulle) , Avance , Contreet (hydroactive) , Contreet-H (hydrocolloid), PolyMem Silver Flexidress , Gelopast , Steripaste , Tenderweap , Viscopaste , Zincaband, Zipzoc

Zinc paste

TenderWet Mepitel (non-adherent) Mepilex (non-adherent, thin, absorbent , border , transfer) Mepitac (fixation tape) Silicone gel sheets: Cica-Care, Mepiform , spenco

Heavily exudating wounds such as dehisced abdominal or pelvic wounds, chronic leg ulcers and infected wounds.Dressing frequency may be reduced depending on level of exudate Moist, necrotic, exudating infected wounds. May be effective in decreasing hyper granulation tissue Infected, Sloughy and diabetic wounds They soften and flatten scar tissue and can be washed and reused, and is usually used under another dressing to reduce pain on dressing changes

Wounds with high microbial burden and moderate to high exudate. Useful in partial and full thickness wounds (burns, donor sites) for complementary use in infected or contaminated partial thickness wounds

Chronic venous leg ulcers , particulary where venous eczema is present and when used in conjunction with appropriate compression bandaging

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Advanced Technologies and Dressings: A. Negative Pressure Therapy Devices: - Controlled negative pressure devices promote vacuum-assisted wound closure. Negative pressure applies noncompressive mechanical forces to the tissue, which allows arteriole to dilate and increases blood flow. Negative pressure is achieved in the wound by positioning suction tube into the foam dressing and connecting this to a pump. - The foams positioned interwound and occluded with a semi-permeable film. - The most widely used negative pressure therapy device is the VAC, which is portable and comes indifferent sizes which allows use on different parts of the body. - The VAC system provides a moist environment, reduces bacterial colonization and localized edema, dead space and the need for frequent dressing changes. It also promotes localized blood flow, granulation, and epithelialization. - It is contraindicated in osteomyelitis and malignant wounds and when necrotic eschars present. - Caution is required for bleeding wounds or potential bleeding when patients are taking anticoagulants.

C.Promogran: - Promogran, a sterile freeze-dried matrixes made up of collagen and oxidized regenerated cellulose - It is recommended for all types of chronic wounds that are free of necrotic tissue and show no signs of infection - Once in place it must be covered with a low-adherent secondary dressing to maintain a moist wound healing environment. - It can be used in conjunction with standard compression therapy when treating venous ulcers. - Frequency of dressing change will depend on the level of exudate. - The matrix absorbs exudate and forms a soft biodegradable gel, which rebalances the wound environment

B. Ceramic Wound Treatment Devices: - These devices are sterile non-woven fabric sachets filled with micro-porous inert ceramic granules. - The ceramic granules have a capillary wicking action on wound exudate and trap excess moisture within the sachets.

38

4. E = Edge - When the epidermal margins of a wound fail to migrate across the wound bed or the wound edges fail to contract and reduce in size, consideration needs to have been given to the T, I, and M first to ensure that all aspects of wound bed preparation have been considered. - The final stage of wound healing is epithelialization, which is the active division, migration, and maturation of epidermal cells from the wound margin across the open wound. - There are many factors which need to be present in order for epithelialization to take place. - The wound bed must be full of well vascularized granulation tissue in order for the proliferating epidermal cells to migrate. - To allow migration, wound edges need to be moist, intact and attached to and flush with the base of the wound. - This also ensures that there is adequate oxygen and nutrients to support epidermal regeneration. - There needs to be a rich source of viable epidermal cells which can undergo repeated cell division particularly at the edge of the wound. - Where cells have become senescent the process slows down or stops completely. - Wounds that have a significant number of fibroblasts that are arrested due to senescence, damaged DNA or enduring quiescence do not heal other factors, such as bacteria or the presence of devitalized tissue, which interfere with epidermal cell growth, have the potential to influence the rate of wound healing. - There are many reasons why the epidermal margin fails to migrate including hypoxia, infection,

-

-

-

-

-

-

-

-

39

desiccation, dressing trauma, hyperkeratosis and callus at the wound margin For wound healing to be effective, there needs to be adequate tissue oxygenation. Decreased oxygen levels impair the ability of the leucocytes to kill bacteria, lower production of collagen and reduce epithelialization It is important to remember that wounds rely on both macro- and microcirculation particularly in the lower limb. A baseline assessment needs to be undertaken to determine the degree of ischemic disease and the ability of the wound to heal without vascular intervention. Wound infection as discussed previously is extremely destructive to a healing wound. Inflammation caused by bacteria causes the extracellular matrix to degrade and therefore epidermal cell migration is interrupted. Wounds become chronic and fail to heal. Dressing products, particularly if adhered or made of fibrous materials, also cause trauma and inflammation of the wound bed which in turn delays healing. It is important to select dressing products which are non-adherent and will not dry out or leave fibers in the wound bed. In certain clinical conditions such as in diabetic neuropathy, there is an over production of hyperkeratosis and callus formation It has also been noted that the epidermis of the skin surrounding venous leg ulcers is thicker than normal skin and highly keratinized If this proliferative, thickened tissue is not removed, wounds will fail to epithelialize.

-

-

-

-

-

-

Failure of a wound edge to migrate is also thought to be associated with the inhibition of the process of normal programmed cell death (apoptosis) which particularly affects fibroblasts and keratinocytes. Cells undergo a characteristic series of changes following mechanical damage to the cell and on exposure to toxic chemicals. Cells become unresponsive and die. Undermining or rolling of a wound edge can also influence the ability of the wound to heal. Undermining can be indicative of a chronic wound and in particular, those wounds that are also critically colonized with bacteria or infected. Rolled edges can present in wounds that have an inflammatory origin such as pyoderma gangrenous or in malignancy. Early diagnosis is important in these cases as failure to provide the appropriate second-line therapy such as oral steroids or tissue biopsy and excision can result in poor healing outcomes.

-

-

-

-

-

Edges Sloping Punched out Rolled Everted Undermining Purple

Measuring a wound at the start of treatment is seen as best practice to enable accurate assessment of the impact of a clinician’s intervention. Subsequent measuring can identify whether or not a wound is failing to heal or deteriorating. The edge of the wound will not epithelialize unless the wound bed is well prepared. Always consider the elements of T, I, and M first to ensure that the use of advanced therapies is appropriate and if used are applied to a well-prepared wound bed to ensure optimal effect. Factors affecting healing of wound edge include: increased age, pain, poor nutrition, medications, e.g. corticosteroids, anticoagulants, immunosuppressants, chemotherapeutic agents, nonsteroidal anti-inflammatory drugs, hydration and lifestyle e.g. high alcohol intake, smoking and obesity

Types of ulcers Venous ulcer Arterial or vasculitic ulcer Basal cell carcinoma Squamous cell carcinoma Tb, syphilis Vasculitic (such as pyoderma gangrenosum)

40

Assessment and management

Goal is to: - Manage exudate (e.g., select causal treatment — compression therapy/ appropriate dressing) - Rehydrate wound edge (e.g., barrier cream) - Remove non-viable tissue (debridement) - Protect granulation/epithelial tissue (e.g., non-adherent dressing) 5. S = Surrounding skin: - Problems of the periwound skin (i.e., the skin within 4cm of the wound edge as well as any skin under the dressing) are common and may delay healing, cause pain and discomfort, enlarge the wound, and adversely affect the patient’s quality of life. - The amount of exudate is a key factor for increasing the risk of peri wound skin damage.

-

Greater moisture exposure reduces skin barrier function and increases the risk of skin breakdown and maceration. This may make patients more susceptible to developing a contact dermatitis Erythema and swelling may also indicate infection, which should be treated according to local protocols. - In addition to the peri wound skin, patients with wounds should also be assessed for problems that may be affecting their skin more widely Goal is to: - Manage exudate (e.g., select causal treatment — compression therapy/appropriate dressing) - Protect skin (e.g., barrier product/atraumatic dressings, avoid allergens). - Rehydrate skin (e.g., emollients). - Remove non-viable tissue (debridement).

41

Type

Product

Product Name

Product details 35 EGP 10 pieces 10x10 cm

Indication of use

Use for absorption of high to very high exudate.

Absorbent pad

Surgical pad

Super-absorbent pad

KerraMax Care

700-980EGP 10 pieces 5x5 cm

Suprasorb-C

320-500 10 pieces 10x10 cm

Foam adhesive

Tegaderm foam Adhesive

700EGP 5 pieces 15x15 cm

-Use to absorb moderate to high exudate. -Use to protect and pad vulnerable areas. -Use with caution on fragile skin.

SILICONE FOAM ADHESIVE

Dimora Silicone Foam (Adhesive)

600-800EGP 10 PIECES 10x10cm

-Use to absorb moderate to high exudate. -Use to protect and pad vulnerable areas. -Suitable for use on fragile skin.

Meplix (adhesive)

500-600EGP 10 pieces 10x10cm

FOAM NONADHESIVE

Biatain Silicone (Non-Adhesive)

42

650-700EGP 10 pieces 10x10cm

Use for absorption moderate to high exudate.

-Use to absorb moderate to high exudate. -Use to protect and pad vulnerable areas.

HYDROCOLLOID - THIN

HYDROCOLLOID - STANDARD

Activheal Foam (Non-Adhesive)

400-580EGP 10 pieces 10x10cm

Duoderm(Extra Thin Film)

800-1000EGP 10 pieces 10x10cm

Dimora (Extrathin) Hydrocolloid dressing

400-600EGP 10pieces 10x10cm

HYDRASEAL

700-800EGP 5pieces 10x10cm

JJ CARE

900-1000EGP 10pieces 10x10cm

-Use for protection of vulnerable skin under devices. -Use to secure other dressings/ packing. -DO NOT USE ON MOISTURE ASSOCIATED SKIN DAMAGE. -Use on superficial wounds where absorbency not required.

-Use for debridement of slough/ necrosis where clinically indicated. -Use as protection of vulnerable skin under devices. -DO NOT USE ON MOISTURE ASSOCIATED SKIN DAMAGE. -Use to secure other dressings/ packing.

Hydrocolloid Dressing 1000EGP 10pieces 5x5cm

HYDROFIBRE

AQUACEL RIBBON

ALGINATE

KALTOSTAT

600-1000EGP 5pieces 2x45cm

1200 EGP 10 pieces 10x20 200 EGP 10pieces 5x5

43

-Use on wounds with moderate to high exudate. -Useful for cavities or uneven spaces. -Can adhere if wound is too dry.

-Homeostatic. -Use to control mild-moderate bleeding

HYDROGEL

NON-OCCLUSIVE ISLAND DRESSING

Duoderm Hydroactive gel

JJ CARE Island

255 EGP 3(amp) 30g

-Use to rehydrate dry slough and necrosis to aid debridement.

688 EGP Pack of (25) 6x6cm

-Use on post-surgical wounds after 48 hours for protection. -Useful for securing other dressings where occlusion is not required. -DO NOT USE ON FRAGILE SKIN.

Dressing

HARTMAN Cosmopor E

612 EGP Pack of (50) 7.2x5cm

NON-ADHERENT WOUND CONTACT LAYER (NON-SILICONE)

HARTMAN Atrauman

500-800 EGP Pack of (30) 10x10 cm

-Use on superficial wounds to protect and line. -Can be used under topical negative pressure foam to protect vulnerable tissue.

SEMIPERMEABLE FILM

3M Tegaderm

1050 EGP Pack of (100) 6x7cm

-Use to secure other dressings. -Use to protect superficial wounds and vulnerable areas.

Medpride

468 EGP Pack of (10) 15x20cm

POSTOPERATIVE DRESSINGS

Smith and

400-600 EGP Pack of (20) 15.5x8.5cm

Nephew Inc Opifix Antibacterial dressing

3m

50-250 EGP Pack of (40) 25x10cm 150-250EGP 20 pieces 5x5cm,9x9cm

Smith and nephew inc

44

450 10g (amp)

-Use on post-surgical wounds immediately after surgery and for first 48 hours. -Useful for securing other dressings. -Use for protecting superficial wounds. -Use on infected superficial wounds. -Useful for drying ischemia areas, diabetic foot wounds.

References 1.

This source was the main core of this introduction, we copied it completely.Wound Care Guidelines and Dressing Formulary

2.

This Cambridgeshire and Peterborough System Wide Formulary is written and supported by: Cambridgeshire Community Services Cambridgeshire and Peterborough Foundation Trust Cambridgeshire and Peterborough Clinical Commissioning Group Cambridge University Hospitals NHS Foundation Trust North West Anglia NHS Foundation Trust Royal Papworth Hospital NHS Foundation Trust Abbas M, Uckay I, Lipsky BA (2015) In diabetic foot infections antibiotics are to treat infection, not to heal wounds. Expert Opin Pharmacother 216: 821-32 Adderley U (2020) National Wound Care Strategy Programme: looking at the impact of COVID-19. Wounds UK 16(2): 11 Angel ED, Lloyd P, Carville K, Santamaria N (2011) The clinical efficacy of two semiquantitative wound-swabbing techniques in identifying the causative organism(s) in infected cutaneous wounds. IntWound J 8: 176–85 Anjali R, Shanthakumar S (2019) Insights on the current status of occurrence and removal of antibiotics in wastewater by advanced oxidation processes. J Environ Manage 246: 51–62 Ayello EA, Carville K, Fletcher J et al (2012) International consensus. Appropriate use of silver dressings in wounds. An expert working group consensus. London: Wounds International. Available at: www. woundsinternational.com Beeckman D et al (2020) Best practice recommendations for holistic strategies to promote and maintain skin integrity. Wounds International, London. Available at: https://www.woundsinternational.com/resources/ details/best-practice-recommendationsholisticstrategies-promote-and-maintain-skinintegrity (accessed 24.06.20) Best EL, Parnell P, Wilcox MH (2014) Microbiological comparison of hand-drying methods: the potential for contamination of the environment, user, and bystander. J Hosp Infect 88(4): 199–206 Bus SA, Lavery LA, Monteiro-Soares M et al (2019) IWGDF Guideline on the prevention of foot ulcers in persons with diabetes. Available at: https:// iwgdfguidelines.org/guidelines/guidelines (accessed 28.07.20) Cooper R (2010) Ten top tips for taking a wound swab. Wounds International 1(3): 19–20 Cooper R, Kirketerp-Møller K (2018) Nonantibiotic antimicrobial interventions and antimicrobial stewardship in wound care. J Wound Care 27(6): 355–77 Cyriac JM, James E (2014) Switch over from intravenous to oral therapy: A concise overview. J Pharmacol Pharmacother 5(2): 83–7

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41. O’Neill J (2014) A review on antimicrobial resistance. Tackling drug-resistant infections globally. https:// tinyurl.com/zmylsav (accessed 17.08.2020) 42. Ousey K, Chadwick P (2019) Bacterial-binding dressings in the management of wound healing and infection prevention: a narrative review. JWound Care 28(6): 370–82 43. Ousey K, Blackburn J (2020) Understanding antimicrobial resistance and antimicrobial stewardship in wound management. Wounds UK 16(2): 36–9 44. Public Health England (2019) English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) Report 2018–2019. PHE, London 45. Roberts CD, Leaper DJ, Assadian O (2017) The role of topical antiseptic agents within antimicrobial stewardship strategies for prevention and treatment of surgical site and chronic open wound infection. Adv Wound Care (New Rochelle) 6(2): 63–71 46. Royal College of Physicians (2017) National Early Warning Score (NEWS) 2 Standardising the assessment of acute-illness severity in the NHS. Updated report of a working party. RCP, London 47. Sandy-Hodgetts K, Carville K, Parsons R et al (2019) The Perth Surgical Wound Dehiscence Risk Assessment Tool (PSWDRAT), development and prospective validation in the clinical setting. J Wound Care 28(6): 332-44 48. Sandy-Hodgetts K, Conway B, Djohan R et al (2020) International Surgical Wound Complications Advisory Panel Best Practice Statement for the early identification and prevention of surgical wound complications. Wounds International, London. Available at: https://www.woundsinternational. com/resources/details/international-bestpracticerecommendations-early-indentificationandprevention-surgical-wound-complications (accessed 21.08.20) 49. Sax H et al (2007) My five moments for hand hygiene’: a user-centred design approach to understand, train, monitor and report hand hygiene. J Hosp Infect 67(1): 9–21 50. Schultz GS, Sibbald RG, Falanga V et al (2003) Wound bed preparation: a systematic approach to wound management. Wound Repair Regen 11 (Supp 1): S1–28 51. Schultz G et al (2017) Consensus guidelines for the identification and treatment of biofilms in chronic nonhealing wounds. Wound Repair Regen 25: 744– 57 52. Serena TE, Harrel K, Serena L, Yaakov RA (2019) Realtime Bacterial Fluorescence Imaging Accurately Identifies Wounds with Moderate-toHeavy Bacterial Burden. J Wound Care 28 (6): 346 53. Sibbald R, Orsted H, Schultz G, Coutts P et al (2003) Preparing the wound bed 2003: Focus on infection

systematic review and meta-analysis of published data. J Wound Care 26(1):20-250 McGow CJ (2019) Prescribing antibiotics “just in case” must be tackled to slow rise in antibiotic resistance BMJ 364 :l553 Munita JM, Arias CA (2016) Mechanisms of antibiotic resistance Microbiol Spectr 4(2): 10: 1128 Nankervis H, Thomas KS, Delamere FM et al (2016) Chapter 6: Antimicrobials including antibiotics, antiseptics and antifungal agents. In: Scoping systematic review of treatments for eczema. NIHR Journals Library, Southampton, UK. Available at: https://www.ncbi.nlm.nih.gov/books/NBK363143 (accessed 8.06.20) National Institute of Allergy and Infectious Disease (2011) Causes of Antimicrobial (Drug) Resistance. National Institute of Allergy and Infectious Disease, Maryland, United States Nazarko L (2016) Good hygiene when dressing wounds. Nursing in Practice. Available at: https://www. nursinginpractice.com/woundcare/good-hygienewhen-dressing-wounds (accessed 19.05.20) NICE (2014) Infection prevention and control. Quality standard [QS61]. NICE, London. Available at: https://www.nice.org.uk/guidance/qs61 (accessed 18.05.20) NICE (2015) Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use (NG15). NICE, London. Available at: https://www. nice.org.uk/guidance/ng15 (accessed 18.05.20) NICE (2017) Healthcare-associated infections: prevention and control in primary and community care [CG139]. NICE, London. Available at: https://www. nice.org.uk/guidance/cg139 (accessed 10.06.20) NICE (2019a) Leg ulcer infection: antimicrobial prescribing [NG152]. NICE, London. Available at: https://www. nice.org.uk/guidance/ng152 (accessed 12.05.20) NICE (2019b) Diabetic foot problems: prevention and management [NG19]. NICE, London. Available at: https://www.nice.org.uk/guidance/ng19 (accessed 31.03.20) NICE (2019c) Surgical site infections: prevention and treatment [NG125]. NICE, London. Available at: https://www.nice.org.uk/guidance/ng125 (accessed 02.04.20) NICE, Public Health England (2019) Summary of antimicrobial prescribing guidance – managing common infections (October 2019). NICE, London. Available at: https://www.nice.org.uk/Media/ Default/About/what-we-do/NICE-guidance/ antimicrobial%20guidance/summaryantimicrobialprescribing-guidance.pdf (accessed 03.02.20)

46

CHAPTER

1 Nourhan Mohamed Fahim , Nada Metwally Ahmed , Ibrahim Ahmed Elsherbini

History of Wound Care The history of wound healing is the history of humankind One of the oldest medical manuscripts known to man is a clay tablet that dates back to 2200 BC. This tablet describes the ‘‘three healing gestures’’

One of the most common ingredients used in plasters was oil. -

1. Washing the wounds. 2. Making the plasters. 3. Bandaging the wound.

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Oil may have provided some protection from infection as bacteria grow poorly in oil. Oil would have prevented the bandage from sticking to the wound as a nonadherent dressing.

Topical wound remedies from ancient societies Animal origin

Vegetable origin

Mineral origin

Butter Bile Blood Egg-White Cochineal Cobweb Grease Meat Milk

Fruits Dyes Bark Leaves Honey Herbs Oils Resin Turpentine Sugar Wine Vinegar

Arsenic Antimony Alum Lead salts Copper salts Clay Potassium salts Mercury salts Zinc salts

Table 1 illustrates the various materials used in topical wound treatments used by ancient or primitive societies.

What the ancients and early moderns referred to as plasters are the present days corresponding to wound dressings. These plasters were mixtures of substances, including mud or clay, plants, and herbs. Table 1 Plasters were applied to wounds to provide protection and to absorb exudate.

Ancient Egypt -

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Egyptian civilization is very prominent and famous among all other cultures. In ancient Egypt (6000 BC), there was the rite of incantation, sorcery, and exorcism. Imhotep was one of the best healers in ancient Egypt, and therefore, was thought to be the Healing God. After

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the death of Imhotep, Egyptians constructed a large number of his temples which were considered to be the healing centres for non-healing diseases and wounds. The Egyptians may have been the first to use bandages either in a belief that closed wound heals faster than open or as a ritual practice because they already knew the art of bandaging during the process of mummification of the dead and were most probably the first people to apply honey to the wounds. They were masters in bandaging. They were successful in the invention of adhesive bandages by applying gum to the linen strip. These bandages were used to draw wound edges together. Honey, grease, and lint were the main components of the most common plasters used by Egyptians. Lint made from vegetable fibre aided in drainage of the wound. Grease made from animal fat provided a barrier to bacteria. Honey appears to be an effective antibacterial agent and has many other healing properties. Honey has been a choice as a topical agent for wounds for 1000s of years and is still part of many advanced wound dressings Another drug most used in Egypt was myrrh, probably because of its quality not to decay and also in a belief that it would fill the wound cavity in the same fashion when it fills the cut wound of the tree. Another drug used in the foul and malodorous wound was frankincense due to its good fragrance. The Egyptians used magic drinks, a mixture of Gum, Milk, and Milk from a woman who has given birth to a son for wound dressings.

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Egyptians also advocated various minerals in the management of wounds. The green copper pigment obtained from malachite and chrysocolla was used as astringents and antiseptics. Mercury compounds were used as antibacterial. Egyptians painted wounds in green colour. Green indicates life, and green paint contains copper, which is toxic to bacteria.

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Ancient Greece & Rome -

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The Greeks were very well aware of the importance of wound closure and were the first to differentiate between acute and chronic wounds, calling them ‘fresh’ and ‘non-healing’, respectively. The Greeks stressed the importance of cleanliness. They recommended washing the wound with clean water, often boiled first, vinegar (acetic acid), and wine. One of the interesting excerpts about wound healing is ‘‘For an obstinate ulcer, sweet wine and a lot of patience should be enough.’’ An early description of the ‘‘four cardinal signs of inflammation’’— rubor, tumour, calor, et dolour (redness, swelling, heat, and pain)— came from the Romans.

Arabic literature of around the 10th and 11th centuries AD - It provides extensive information -

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about surgery and medicine. These texts are extensively based upon Roman and Greek written theories.

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In his book, 'The Arrangement of Medical Knowledge for The One Who Is Not Able to Compile A Book for Himself', Albucasis described 18 case histories from his experience, out of which eleven of the cases were for the treatment of wounds. - Islamic medicine made a very important scientific contribution to the field of chemistry. - The Arabs discovered distillation and crystallization necessary in the manufacture of medicine. - They also founded the science of pharmacy. - Albucasis quoted four methods of stilling an arterial haemorrhage from the wound: Cautery, division of vessels, ligatures, or styptics. - His most famous book 'Al-Tasreef/VedeMecum' in volume number 30 has described detailed literature about wounds, ulcers, and injuries and their treatment. 6. Ali Ibn Isa Kahhal/Jesu Haly (1039 AD) - In his famous book 'Tazkarat-ulkahhalein', he mentioned the procedures of eye surgeries and according to Paulus Aegineta, eye wounds and their treatment. 7. Ibn Zuhr/Avenzoar (1091–1162 AD) - He had been a famous surgeon of the time; He described the wound and its treatment in his famous and most accepted book 'Kitab-ut-taiseer'. - He was an expert in the operations of renal stones, fistula, tracheal obstruction, and cataracts. 8. Isma'il Jurjani (12th century AD) - In his most accepted book 'Zakheera Khuarzam Shahi', in jild number seven, he has given detailed and fine descriptions of the wound and its treatment.

1. Zakariya Al Razi/Rhazes (864 or 865–925 or 935 AD) - Zakariya Al Razi/Rhazes described the categories of wounds and their management in his famous book 'Kitab-al-Hawi/Liber Continens in volume twelve. - Regarding surgery, it is focused specifically on bloodletting and cauterization. 2. Ali Ibn Abbas Majoosi (930–994 AD) - In his book 'Kamil-al-sana't/Liber Regius', He gave detailed information about the Amraz-e-zahira. 3. Ibn Sina/Avicenna (980–1037 AD) - He has mentioned types of wounds and ulcers in his famous book 'AlQanoon Fit Tib/Alcanon' in jild number four. He instructed to wash the wounds with wine. 4. Abu Sahl Masihi (10th century AD) - He described the wound and its treatment in his famous book 'Kitabal-Mi'at' in chapter number 61 named Bathoor wa qurooh and again in chapter number 98 named Amraz-ejild. 5. Albucasis/Abul Qasim Zohrawi (936–1036 AD) - By the end of the 10th century, the dominant centre of Islamic medicine had moved from Baghdad to Cordoba (present-day Spain) and he became its most famous teacher. - He earned a reputation in Islamic Spain for his surgical skills - He was a surgeon who realized the importance of anatomy in surgery. - His methods of wound treatment were firmly rooted in Galen, and he tried to encourage suppuration by applying various ointments. - His teaching came to influence early European surgery.

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He advocated the appliance of a plaster cast if bleeding is huge from the wound. 9. Ibn Baytar (1197 AD) - In his reputed book 'Kitab-al- jaameal-mufradat' has described many planters, mineral, and animal origin drugs, and also among them, the drugs, used for the treatment of wounds. 10. Najeeb-ud-din Samarqandi (13th century AD) - In his famous book 'Kitabul-asbaabwa-alamaat' jild number 3, has mentioned a fine description of the surgery. 11. Ibn Khateeb (1313 AD) - He has described crude drugs widely used in the treatment of ulcers/wounds in his famous book 'Kitab-ul-Advia

with fellowship programs offered at some academic centres. In summary, the first wound treatments were described 5 millennia ago. Since then, various principles of wound care have been passed on from generation to generation. It is essential to understand the historical aspects of wound treatment (both successes and failures) to continue this progress and provide future direction.

In the 19th century -

The antiseptic technique was a major breakthrough. The introduction of antibiotics helped control infections and reduce mortality. At the present time

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There are more than 5,000 wound care products. Most modern dressings contain materials that are highly absorbent, such as alginates, foam, or carboxymethyl-cellulose. There are growth factors, advanced honey-based dressings, and hypochlorous acid–based cleansers. Bioengineered tissue, negative pressure therapy, and hyperbaric oxygen therapy have changed the way we treat a lot of chronic wounds today. There are more than 1,000 wound healing centres within the United States today and wound healing has become a speciality,

50

CHAPTER

2 Eman Esam Elhofy , Wafaa Mahmoud Abdellatif , Ibrahim Ahmed Elsherbini

Wound Healing -

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8. Select and apply the appropriate products pertinent to all types of wounds. 9. Encourage ongoing initiatives for wound care education. - Using a coordinated strategy can lead to better results in terms of standardisation, teaching, and research, as well as more consistently applying evidence-based approaches to wound care. - This manual is meant for anyone who has an interest in and enthusiasm for caring for wounds, not just clinicians specialising in skin and wound care and other healthcare professionals.

An injury to living tissue that results in a break in the continuity of the epithelial lining of the skin or mucosa due to a generally external damage is referred to as a wound (i.e., physical or thermal, typically one in which the skin is cut or broken). It is essential that those involved in the care and management of wounds should have at the very least a basic understanding of the physiology of the natural processes involved in wound healing.

The Provincial Skin and Wound Care Manual will: 1. Assist the healthcare professional in assessing the patient with a wound and making decisions on the patient's treatment and management. 2. Provide a complete grasp of the wound healing process and how this impacts the patient’s general state of health. 3. Identify risk factors that affect and slow the healing of wounds. 4. Concentrate on and put into practice the best methods for evidence-based wound care. 5. Identify/adapt methods for avoiding the recurrence of wounds. 6. Become more knowledgeable about developing technical wound assessment and documentation abilities. 7. Become familiar with the most cuttingedge wound care technology available.

Anatomy and physiology of the skin

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The cells initiate protein synthesis required for the production of keratin.

The structure of the skin -

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The skin makes up to 15-20% of the body's weight, making it the largest and most noticeable organ. It receives 300 ml/minute, or about one-third of the body's blood flow. The epidermis and dermis are the two layers that make up healthy skin. The hypodermis, a layer of loose connective and fatty tissues that integrates with the deepest layer of the dermis to provide heat insulation and protection from physical forces, is located underneath the dermis.

3- Stratum granulosum (granular layer) The process of keratinization begins. 4- Stratum lucidum (clear layer) A soft gel-like material that eventually turns into keratin fills the cells. Only on the palms of the hands and soles of the feet, where the skin is thicker, is this translucent layer visible. 5-Stratum corneum (horny layer) The epidermis's topmost layer is this one. Keratin has accumulated inside the cells. Desmosomes are necessary for preserving skin integrity. These intercellular connections provide additional adhesion and strength to maintain neighbouring keratinocytes together. As dead surface cells are continually removed and replaced by cells from the deeper layers, the process of repair and regeneration never stops. The epidermal barrier that prevents water loss from the skin is provided by the stratum corneum. A continuous cellular matrix that is lipid-enriched surrounds the cells. The loss of lipids and consequent drying of the epidermis that results from constant exposure to fluid, such as from wound exudate, incontinence, or excessive washing, impairs the skin's ability to act as a barrier.

1. Epidermis -

The skin's topmost, thinnest, stratified, avascular layer. - It varies in thickness in different parts of the body, being thickest (1.6 mm) on the soles of the feet and the palms of the hands, and thinnest (0.04 mm) on the eyelids. - - Growth factors promote the differentiation or regeneration of the epidermal layer. - It takes approximately 3 - 4 weeks. The primary cells in this layer are Keratinocytes (protein-producing cells) and Melanocytes (colourproducing cells). The primary functions of this layer are Protection and Regulation. It is composed of five layers of stratified squamous epithelium:

Dermal–epidermal junction (Basement membrane zone)

1 - Stratum basale (basal layer)

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Cells go through mitosis. It takes roughly 28 days for cells to migrate from the stratum basale to the stratum corneum's outer layers. Additionally, it has Langerhans cells, which are important for immunological function, and melanocytes, which create melanin pigments.

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2- Stratum spinosum (prickle cell layer)

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It gives the skin strength and keeps the epidermis and dermis from separating. Blistering can happen if there are too many shear stresses at the epidermisdermis junction, causing the epidermis to detach from the dermis. It is made up of proteins including non-fibre forming collagen and fibronectin, which helps with hydration retention and the adherence of healing

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elements (adds thickness to the skin). The epidermal appendages, such as sweat glands and hair follicles, are anchored by it.

2. Dermis -

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It is the layer between the epidermis and the subcutaneous Tissue. It is thicker than the epidermis. It varies in thickness from 1 mm - 4 mm (The densest area is on the back) It contains the cells that are principally in charge of promoting wound healing, including lymphocytes, fibroblasts, and mast cells. Fibroblasts secrete collagen (protect by controlling microbial invasion). Collagen, reticulum, and elastin fibres make up its structure. a framework that houses the hair follicles, sweat glands, sebaceous glands, blood arteries, lymphatic capillaries, and nerve endings. Eccrine and apocrine sweat glands travel through the epidermis and emerge as pores on the skin's surface. Through the sweat gland, poisons, salts, and water are expelled. The sebaceous glands open into a hair follicle and secrete sebum. The primary functions of this layer are strength, nutrition and structural support.

Physiological changes in ageing skin -

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3. Subcutaneous Tissue -

The epidermis becomes thinner as fewer active basal cells are left in the layer. Slower cell turnover, resulting in slower healing. Fewer Langerhans cells, which results in a delayed inflammatory response. Tactile sensitivity lessens and patients experience reduced acuity of pain perception. Loss of subcutaneous fat results in less pressure dissipation. Vascular walls become thinner and fragile, and the skin bruises more easily. Skin splits easily as the dermoepidermal junction flattens, weakening the bond between the two layers.

Types of tissue injury

It holds the epidermis and dermis to the underlying bodily tissue and provides support for them. It is sometimes referred to as the Hypodermis. This layer's main purposes include body form, insulation, protection, and energy.

1. Environmental Injuries: -

Wind: -

PH of the skin -

If the skin comes in contact with something that has a pH outside its normal range, the potential for harm to the skin is present. The closer something gets to a pH of 1 or a pH of 13, the more acidic or alkaline it becomes, and it has the potential to cause serious burns to the skin

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The normal skin pH is 5.5. PH. A skin pH of 5.5 means that the skin is acidic.

Temperature Irregularities: -

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Wind can have an excessive drying effect on the skin, leaving it more at risk of breakdown.

Extreme cold can harm skin by causing frostbite or frostnip.

When the wind chill is -22 Co, frostbite might develop in 15 minutes. -

Humidity: -

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Excessive skin moisture can change the pH balance of the skin and lead to maceration.

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It is the inadvertent removal of the epidermis, with or without the dermis, by mechanical means. - It can be avoided by: 1. recognition of fragile, vulnerable skin, 2. appropriate application and removal of tape, 3. use of solid-wafer skin barriers or skin sealants under adhesives, 4. use of porous tapes, 5. Avoidance of unnecessary tapes.

Sunlight–Exposure to UV rays: -

It can lead to skin cancer, sunburn (first or second-degree burns), compromised immunity, and long-term skin damage.

2. Mechanical Injuries: -

Friction: -

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Two surfaces rubbing against one another can also lead to skin breakdown; popular locations include the elbows and heels.

3. Chemical Injuries: -

Shear force: -

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This is created by the interaction of both gravity and friction (resistance) against the surface of the skin. - Shear force injuries result in substantially more severe outcomes since the harm typically begins at the level of the bone or deep tissue and later manifests on the skin's surface. - This frequently happens when the head of the bed is too high, above 30o, or when a patient is transferred using improper transferring techniques. Pressure: -

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wastes build up in the interstitial tissue. - Anoxia and cellular death are the results. Prevention is the key. Epidermal Stripping:

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The most common form of mechanical damage. When pressure exceeds capillary pressure, which is typically defined as being between 12 and 32 mm Hg, cellular damage results. Tissue ischaemia develops with continued strain, and metabolic

Irritant contact dermatitis is a reaction that can occur when there are chemical irritants present. In the presence of a potent irritant, skin injury may become apparent within a short period of time (such as diarrhoea). Chemical dermatitis can be distinguished from an allergic reaction by its irregular borders and always requires the presence of drainage or chemicals. Faecal incontinence - faeces contains enzymes that are damaging to the skin. Harsh solutions (for example, betadine, hydrogen peroxide, alcohol and salvodil) - cause chemical irritation by destroying or eroding the epidermis. The pH of drainage around percutaneous tubes, drains, or catheters can erode the epidermis.

Physiology of wound healing -

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The body's replacement of injured tissues with living tissues is described as wound healing. This complex and

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dynamic process involves several cellular and matrix components that work in concert to restore the integrity of injured tissue. The type of injury and the degree of tissue loss determine the healing time. Healing takes longer and is more complicated in deep wounds where vasculature has been destroyed compared to superficial wounds where just epithelial tissue is harmed. Healing goes through complex, multistep processes, which include inflammation, collagen metabolism, wound contraction and maturation.

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1. Haemostasis -

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As soon as a wound is sustained, haemostasis occurs. First, the body's defences attempt to prevent bleeding by restricting the nearby blood vessels Platelets adhere to exposed collagen in the sub-endothelium of blood vessels. Fibrin combines with platelets and trapped erythrocytes to form clots. This temporary plug is later replaced by a more durable fibrin clot. This procedure goes quickly and takes several hours.

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2. Inflammatory Phase -

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The body's defence mechanisms trigger an inflammatory response as soon as an injury occurs. The first four to six days following a wound are spent in this period of healing. Injured blood vessels bleed into the wound, and platelets adhere to exposed collagen in the subendothelial layers of the walls of the damaged blood vessels.

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The platelets flatten and release substances, including proteins, which cause the platelets to become sticky. Fibrin joins with platelets and erythrocytes that have been trapped to form a clot that obstructs the damaged blood vessels. Activated platelets release growth factors, including platelet-derived growth factor (PDGF) and epidermal growth factor (EGF). The numerous proteins involved in directing the series of activities necessary for wound healing are referred to as "growth factors." There is a continuing study in this area, however, it is unknown how many growth factors are related to wound healing. Growth factors play a significant part in creating the channels for cell communication during the healing of wounds. PDGF aids in the development of granulation tissue, collagen, and ground material as well as the initial inflammatory phases of healing. EGF has a significant role in epithelialization and the formation of granulation tissue. These growth factors act as chemoattractant chemicals, which facilitate the migration of neutrophils to the area. On the first day, neutrophils and monocytes may be seen in the wound and are in charge of starting the wound-cleansing process by removing germs, dead tissue, and debris from the wound using a procedure called phagocytosis. Inflammation leads to an increase in vasodilation and vessel permeability. Serotonin and histamine are produced, increasing capillary permeability and permitting plasma leakage, which in

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turn causes fluid to build up in nearby tissues. The patient feels localised discomfort as a result of the increased blood flow and oedema, which also cause heat, erythema, and swelling. Excessive fluid drains from the wound tissue as exudate. Wound fluid from acute wounds is rich in growth factors that have been shown to promote tissue repair at the end of the acute inflammatory phase neutrophils decay and are themselves phagocytosed by macrophages that have matured from monocytes. Macrophages continue to undertake autolytic debridement of the wound by phagocytosing and digesting bacteria, wound debris, and necrotic tissue.

4. Maturation Phase (also called reconstruction or remodelling phase) -

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3. Proliferative Phase (comprised of granulation and epithelialization) -

Depending on the severity of the injury, the process of "new" tissue growth or proliferation is separated into two phases: Granulation and Epithelialization. 1. Granulation: Granulation is the process by which all partial and fullthickness wounds heal. The dermal cells (Fibroblasts) in the wound bed and peri-wound borders start the natural healing process because the epidermal layer has been damaged. Normally, 12 to 48 hours after the original injury, granulation will start. 2. Epithelialization: Superficial wounds heal by Epithelial Regeneration. The wound will be resurfaced with natural skin through the natural process of epidermal cell keratinocytes development and differentiation. The process is usually complete after 3 - 4 weeks.

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The maturation phase, also known as reconstruction or remodelling, may take up to two years to complete. Extracellular matrix components change Collagen fibres are reconstructed, giving greater tensile strength to the new tissue Scar tissue that has recently formed realigns the internal structure to make it more durable. The wound's strength will only increase by up to 80% after healing. If collagen production outpaces collagen degradation, abnormal scarring will result.

Types of wound healing -

A wound may heal through the following ways: 1- Primary intention 2- Delayed Primary intention 3- Secondary intention

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1- Primary intention: -

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In primary closure, which may involve a surgical incision, the edges of the wound are brought together and approximated using sutures, staples, or adhesive tapes. Healing occurs mainly by connective tissue deposition. Epithelial migration is short-lived and may be completed within 72 hours.

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3- Secondary intention: -

2- Delayed Primary intention (Tertiary intention)

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It is a combination of healing by primary and secondary intention, and is usually instigated by the wound care specialist to reduce the risk of infection. Before the wound is surgically closed, it is cleaned and watched for a few days to make sure there is no sign of infection. Examples of wounds that are closed in this way include traumatic injuries such as dog bites or lacerations involving foreign bodies.

It represents a method requiring no specialised tools. When contaminated or filthy wounds are made, they can be used to open the skin for a few days, allowing the soft tissues to drain (and preventing the build-up of microorganisms in a small space).

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Wound edges are not rounded off in secondary intention healing. There is tissue loss and skin edges are far apart, so they heal from the base upward by granulation tissue. Granulation tissue is the new tissue composed of capillary loops, collagen and the ground substance, it is red in colour and has a slightly rough granular texture. Pressure ulcers and open excision are two examples of wounds that heal through secondary intention.

Factors affecting wound healing 1. Infection -

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When determining whether a wound is infected, the clinician should be familiar with the following four terms: 1- Contamination: Presence of nonmultiplying bacteria within a wound, which accounts for the majority of the microorganisms present on the wound surface. 2- Colonization: Presence of bacteria which are multiplying but are producing no host reaction. This includes skin commensals such as Staphylococcus epidermis and Corynebacterium species, whose presence has been shown to increase the rate of wound healing. 3- Critical Colonization: This term describes a wound where the bacterial burden is increasing as a result of organism multiplication, which is starting to impede healing. Locally, but not generally, critical colonisation triggers the body's immune response. 4- Infection: This term describes the presence of bacteria that are growing and triggering a reaction in the host. Invading nearby tissue, pathogenic bacteria multiply and cause harm to the host. This could cause a systemic infection if left untreated.

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3. Compromised immune system -

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When the immune system is compromised, all phases of healing are delayed, and patients are at increased risk of infection. Patients with cancer, those who are HIV-positive, those who are malnourished, and elderly and frail patients are among those who have a compromised immune system. Some medical procedures, such as radiation therapy, chemotherapy, steroid therapy, and immunesuppressive therapy, can have adverse effects that compromise the immune system.

4. Smoking N.B: tobacco act as a potent vasoconstrictor -

2. Low oxygen and decreased tissue perfusion -

for very thin, ill, immobile, or other atrisk patients. Collagen synthesis and angiogenesis both require oxygen. Since haemoglobin carries the majority of the oxygen in the blood, patients with wounds who have low haemoglobin have slower wound healing. Tobacco acts as a potent vasoconstrictor and patients who require surgery are recommended to stop smoking pre- and post-operatively

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Unrelieved pressure may contribute to tissue perfusion impairment through arterial occlusion or vasoconstriction, peripheral vascular disease, diabetes mellitus, and other conditions. Pressure-relieving devices such as mattresses and cushions are available

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Nicotine and its primary metabolite, cotinine, have serious effects on Endothelial injury, atheromatous lesion growth, smooth muscle tone and blood viscosity. For more than an hour following the consumption of just one cigarette, the peripheral blood flow is reduced by at least 50% due to the nicotine absorbed from cigarette smoking. Carbon monoxide reduces the amount of oxygen in the blood by binding to

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haemoglobin in place of oxygen, which can slow the healing process. 5. Stress - Stimulates peripheral blood vessel vasoconstriction, which ultimately can reduce tissue perfusion. - Stress also raises levels of naturally occurring steroids in the blood, which can lessen inflammation and slow the development of fibroblasts and keratinocytes.

9. Hyper-granulation -

6. Hypertension -

Systolic hypertension in particular is the second most predictive risk factor for PAD.

7. High cholesterol levels -

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Elevated Cholesterol levels, especially elevated LDLs, are thought to be an important risk factor for the development of atherosclerosis and PAD.

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8. Metabolic Disorder -

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Other conditions such as COPD, PVD, CHF, and Hypovolaemia are all examples of disease states which can result in a reduced supply of oxygen to wounded tissue.

A variety of metabolic disorders can hinder the ability to heal wounds. Diabetes has a direct impact on the body's glucose supply, the health of peripheral blood vessels, and peripheral sensation, which blocks pain and discomfort. As a result, it can affect how aware an individual is of an injury or complications. High glucose levels impair leucocyte function, inhibit collagen synthesis and bundling processes, and interfere with the development of granulation tissue. Additionally, it reduces oxygen and raises the risk of infection. Metabolic waste products may accumulate or be insufficient as a result of renal disease. Bowel disorders can interfere with nutritional absorption.

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Granulation tissue that has continued to grow above the level of the wound bed is referred to as "hyper-granulation tissue," also known as "overgranulation tissue." Once granulation tissue has completely covered the wound, epithelial cells begin to migrate and proliferate from the edges of the wound or from islands within the wound bed. When hyper-granulation tissue is present, the raised tissue inhibits the migration of epithelial cells and healing is impaired. Hypergranulation has been reported as a common problem related to gastrostomy tubes and can occasionally be found around tracheostomy and drain sites. Topical steroid preparations are sometimes used to reduce and flatten hyper-granulation tissue. Occlusive dressings can sometimes result in a wound becoming overgranulated. When this occurs, changing from an occlusive dressing to a simple foam dressing can be helpful in reducing hyper-granulation. In some cases, hyper-granulation tissue resolves on its own as the wound heals, and wounds shrink as they close.

10. Medications -

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Drugs like steroids can suppress granulation and lessen the inflammatory response. The neighbouring cells' integrity, which is crucial to proliferation, can be

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impacted by chemotherapy and radiotherapy. These treatments can also deplete essential immunologic agents, energy and oxygen sources including RBCs. Vasoconstrictors can reduce the amount of circulatory volume available to healing tissue.

Nutritional factors in wound management -

11. Surgery -

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Certain anaesthetic agents cause vasodilatation that restricts the skin’s natural ability to alter the diameter of peripheral blood vessels, thus controlling thermoregulation. These patients may experience excessive shivering after surgery. This drop in body temperature could affect healing. To reduce heat loss, it's essential to cover up with cosy blankets.

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Biology of wound healing -

12. Advanced Age -

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There is a decline in fibroblasts, which are directly responsible for the synthesis of collagen or the growth of new tissue. There is also a tendency for nutrient and fluid intake to decline. Concurrent diseases of the respiratory and circulatory systems that can limit tissue perfusion are also common.

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13. Alcoholism -

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It can impair liver function, subsequently altering the production of protein and other essential elements needed for tissue repair.

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14. Nutrition -

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Maintaining skin integrity, fostering tissue restoration, and minimising wound complications depend on the prevention and treatment of nutritional deficiencies. Malnourished patients are at greater risk for complications including longer length of stay and more infections, leading to increased healthcare costs. Any wound management strategy won't work unless nutritional deficiencies are addressed.

A balanced diet that includes enough protein, carbohydrates, fats, vitamins, and minerals helps to maintain normal, healthy skin integrity. If skin becomes damaged, an increased dietary intake of some substances, such as vitamin C, for collagen formation may be indicated and beneficial.

When evaluating patients with wound complications and creating care plans, it's helpful to have an understanding of how nutrients are used during each stage of the healing process. Collagen formation is stimulated by fibroblasts, the formation of which requires the specific enzyme lysyl and prolyl hydroxylase. The activity of these enzymes requires oxygen, Vitamin C and iron as co-factors. This enzyme requires manganese as a cofactor. The final cross-linking of the collagen requires the enzyme lysyl oxidase and requires copper as a co-factor. Epithelialization needs both oxygen and a moist environment to occur.

Hydration Status: -

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Optimal intravascular volume and regional tissue perfusion depend on adequate hydration for electrolyte balance. In a moist environment, epidermal cells have been shown to migrate more

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quickly and cover the wound surface earlier. For wounds to heal, the right amount of fluid supplementation and avoiding dehydration and overhydration are essential.

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substrates that form cell membranes. The production of prostaglandins and other inflammatory and immune system regulators depends on fatty acids.

Specific Nutritional Requirements:

Vitamins and Minerals:

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The extensive process of wound healing necessitates an optimal nutrient supply, sufficient oxygenation, and blood flow, as well as numerous synthesis- and energy-intensive reactions. Protein: - Protein: Amino acids and proteins are necessary for the synthesis of proteins, including the enzymes involved in the healing process. - By altering antibody response times and lowering infection resistance, protein depletion weakens the immune system. - A lack of protein causes interstitial oedema and hypoalbuminemia, which slow the cellular exchange of nutrients and reduce skin integrity and resiliency, making the skin more vulnerable to injury.

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Carbohydrates and Fats: -

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Glucose, the simplest form of carbohydrate, is the preferred fuel for wound repair. When cells need glucose to function, the body breaks down protein and fat to provide the necessary energy. Fatty acids are needed for cell membranes, and deficiencies may impede wound healing. Unsaturated fatty acids such as linoleic and arachidonic are essential components of triglycerides and phospholipids,

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Vitamin A: - Vitamin A is essential for preserving the body's normal humoral defence system and reducing wound infection-related complications. - It promotes fibroplasia and collagen accumulation, hastens the healing process and enhances tensile strength. - Vitamin A has also been used to counteract the catabolic effect that steroids have on wound healing. Vitamin C: - It serves as a cofactor in the hydroxylation of proline, which is necessary for the production of collagen. - It has also been demonstrated to enhance the cellular and humoral response to stress. - Old wounds may reopen in vitamin C deficiency due to extracellular matrix degeneration and loss of tensile strength. Vitamin K: - Vitamin K is required for the hepatic synthesis of clotting factors II, VII, IX and X. - A vitamin K deficiency increases the risk of infection and wound complications, excessive bleeding and the development of haematomas. B-Complex Vitamins: - Cofactors in enzyme systems are essential for the protein, carbohydrate and fat metabolism

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and hence they are implied in the wound repair system. - A lack of B-complex vitamins, especially pyridoxine, pantothenic acid, and folic acid, suppresses the production of antibodies and leukocytes, which makes people more susceptible to infection and slow wound healing. - Thiamine (B1) deficiency could affect collagen synthesis. Zinc: - It is a component of bio-membrane and is necessary for RNA, DNA and ribosome stabilization. - Zinc deficiency hinders wound healing by slowing epithelialization, weakening the healing process, and decreasing collagen synthesis. Iron: - Iron is necessary for the hydroxylation of lysine and proline in the formation of collagen. - Anaemia could lead to hypovolaemia and tissue hypoxia. - Depressed inflammatory response, bacterial infection, and postponed wound healing may result from poor blood supply and low tissue oxygenation. Copper and Manganese: - Copper is a crucial component of the enzyme lysl oxidase, which catalyses the creation of stable collagen cross-links. - Manganese activates specific enzymes responsible for the glycosylation of procollagen molecules and the synthesis of proteoglycans. - These mineral deficiencies may alter collagen synthesis and slow wound healing.

Nutritional screening/assessment -

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The use of risk assessment tools, which should not only concentrate on the treatment of existing wounds but also the prevention of skin breakdown, could be the most effective way to prevent wound complications. Ideally, when risk assessments are completed, every patient must be individually assessed for co-existing risk factors for wound complications and malnutrition.

Risk Factors for Malnutrition and Wound Complications: Admission Diagnoses: - Patients admitted for nutritional risk include those with neurological deficits, GI bleeding or obstruction, pulmonary, renal, or hepatic failure, and sepsis from pneumonia or urinary sources. - Poorly controlled diabetes could also lead to impaired wound healing and poor wound outcome. Certain Circumstances - The use of steroids may slow the rate of neovascularization and wound healing as well as reduce collagen deposition and tensile strength. - Complex injuries involving multiple tissues and organs, infections, sepsis, and trauma increase the need for energy and protein; under these conditions, impaired healing may result from insufficient dietary intake. - Prolonged immobility secondary to fractures or decreased mental status places patients, particularly elderly patients, at greater risk of tissue breakdown and subsequent increase in morbidity and mortality.

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Weight Status: - Compared to patients who did not lose weight, patients whom self-reported unintentional weight loss of more than 10 pounds (4.54 kg) within the preceding six months of admission for elective surgery had significantly higher mortality rates. - Additionally, it has been reported that patients with decreased body weight are at increased risk of developing pressure sores. - Weight measurements can be influenced by a variety of things. Rapid changes in weight status can indicate significant changes in hydration status. - Gain or loss of more than 0.5 kg over 24 hours in the absence of significant fluid shifts may indicate measurement error and should be rechecked.

Transferrin: 2.12-3.66 g/L - A protein that binds iron, transferrin is frequently used to determine a person's nutritional status. Due to its smaller serum pool and 8–10-day half-life, it is more sensitive and specific than albumin. - According to Albina, serum transferrin concentrations under 150 mg/dL (1.5 g/L) were significantly predictive of slow wound healing or wound infections. - In a retrospective study, it was found that serum transferrin measurements predicted spontaneous fistula closure. - Conditions such as iron deficiency anaemia, transfusions, massive blood loss, chronic infections or inflammation could affect transferrin levels. - Blakburn et al. has categorized serum transferrin levels 100-150 mg/dL (11.5 g/L) as moderate malnutrition and less than 1.0 g/L as severe.

Biochemical Indicators: Albumin:35-50 g/L - Serum albumin, an indicator of visceral protein status, is widely used in nutrition screening. - This protein regulates the plasma osmotic pressure and carries metals, drugs, hormones, and other metabolites throughout the bloodstream. - Although serum albumin is subject to fluctuations in fluid status, it still remains a cost-effective/sensitive indicator of changes in clinical status such as infection, hydration and starvation. - Serum albumin levels less than 21 g/L are indicative of severe malnutrition, according to Blackburn et al. - When screening for pressure ulcers, patients with a serum albumin less than 25 g/L should be categorized as high risk.

Total Lymphocyte Count (TLC): - Total lymphocyte count (TLC) has been used as an indirect indicator of dietary intake and immune function. - Pinchkofsky-Devin et al. and Allman et al. have found that lymphopenia (TLC less than 1200 and 1500 cells/ mm or 1.2 - 1.5 x 10 cells) was associated with pressure ulcers. - Total lymphocyte count of 800 -1200 mm or 0.8- 1.2 x 10 cells are classified as moderate malnutrition and less than 800 mm or less than 0.8 x 10 cells as severe malnutrition. Haemoglobin, Haematocrit and Serum Ferritin: - They have been correlated with the risk of developing pressure ulcers and are excellent indicators of eventual mortality.

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Wagner has advised testing the triad of haemoglobin, haematocrit, and ferritin to distinguish between true iron deficiency anaemia and chronic anaemia, as the latter is common among patients with pressure ulcers. Determination of vitamin B12 and folate levels could then be carried out to diagnose other common nutritional anaemias.

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Energy Requirements: 1. Calculating the necessary amounts of protein and energy is the first step in creating a proper feeding schedule. 2. Wolfe et al. has determined that the maximum rate of glucose oxidation could be reached with 35 Kcal/Kg. Wagner recommends a range of 25 35 Kcal/Kg for estimating calorie requirements. 3. The agency for Health Care Policy and Research (AHCPR) guideline Treatment of Pressure Ulcers recommends 30 – 35 kcal/Kg for patients with pressure ulcers. - Wagner suggests that traumatised, septic, stressed patients fall at the higher end of the scale, while young, unstressed, malnourished patients fall at the lower end of the scale. It would be prudent to agree with Wagner on this point. - AHCPR additionally advises using the Harris Benedict formula to determine energy needs and to adequately account for "injury factors" like infections, fractures, and open wounds that will raise estimates of energy expenditure. - The energy requirements suggested by Jackob’s protocol as a standard and guide (25-30 Calories/kg for stage I and Stage II wounds, 30 to 40 Calories/ kg for Stage III and Stage IV wounds).

Serum cholesterol: - Low serum cholesterol (less than 4.14 mmol/L) has been linked to measurable mortality and unfavourable results in older adults. - The decrease in membrane phospholipids will affect cellular function resilience and skin integrity. Risk assessment tool: - The Braden Scale is designed to predict the likelihood of developing pressure sores; it is not intended to identify patients at high risk for delayed wound healing or wound complications. The committee advises routine screening of patients before and after surgery. -

The Committee recommends using one or more of the following criteria: 1- Serum Albumin Less than 3 2- Pre-albumin Less than .17 3- Recent Weight Loss Greater than 7.5% in 3 months 4- Total lymphocytes Less than 1.8 x 10^3 cells 5- Urea Greater than 7

Therapeutic Plan: -

determine the need for nutrition supplements. Dietitians should use their clinical judgment to determine appropriate body mass when calculating energy, protein and fluid requirements.

Patients should be assessed by a dietitian to ensure that nutritional requirements are being met and to

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Protein Requirements: - The Recommended Dietary Allowance (RDA) for protein, based on 0.8 g/kg, is insufficient for patients with wounds. - As the stress factor increases with injury, infection or open wounds, intake of protein should increase. - AHCPR guidelines advise consuming 1.25 to 1.5 g/kg of protein daily, but they acknowledge that some patients may require more protein depending on their wound type and treatment objectives. - The use of a very high protein formula (up to 2.9 g/kg) has been linked to improved nitrogen balance and faster healing of decubitus ulcers, according to research by Chernoff et al. - Jackob’s protocol as a guide to determine protein requirements of patients with wounds (1 gm/kg for Stage I, 1.2 gm/kg for Stage ii, and 1.5gm/kg for Stage III and IV). - However, patients with impaired renal function should have their individual protein requirements evaluated.

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Fluid Requirements: - A general rule of thumb is to provide 1 mL of fluid for every kcal of energy consumed, with a daily minimum of 1500 ml. - Patients' medical conditions, including cardiac status, renal function, and exudative losses from open wounds, should be taken into account when determining their fluid requirements. - Patients on air-fluidized beds need to increase their fluid intake to another 10-15 mL /kg of body weight above those recommended to prevent dehydration.

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Jackob’s protocol, (25-30 cc/kg for Stage I and Stage II wounds, 30–35 cc/kg for Stage III wounds and 3040 cc/kg for Stage IV wounds), except for patients on air fluidized beds.

Vitamins and Minerals: - Patients' medical conditions, such as renal status, gastrointestinal function, and altered immune status, should be taken into account when evaluating vitamin/mineral supplementation. - Three nutrients that are frequently associated with wound healing are Vitamin C, Vitamin A and zinc. - Individual supplements up to 10 times the Recommended Daily Allowance for water-soluble vitamins may need to be added to the patient's daily dietary intake when specific nutritional deficiencies are identified. - The recommended dietary allowance (RDA) for Vitamin C is 90 mg and 75 mg respectively for males and females above 19 years. This amount is easily achieved from dietary sources such as citrus fruits, green peppers and tomatoes. - It has also been shown that the Vitamin C status of hospitalized patients deteriorates during their hospital stay. - The addition of Vitamin C supplements to these patients' diets may help them heal their wounds more quickly after surgery or injury if they already have a marginal Vitamin C status. - They advise that seriously ill and injured patients be given 1 to 2 g of ascorbic acid daily, starting promptly and continuing until convalescence is well advanced

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(until skin coverage is almost complete in burn patients)”. The Committee advises supplementation in accordance with Jackob's Nutrition Protocol (250– 750 mg/day for Stage II and Stage III wounds) for patients without renal failure and kidney stones. For adult males and females, the RDA for zinc is 11 and 8 mg per day, respectively. Seafood, oysters, liver, meat, and milk are all good sources of zinc in the diet. Patients who have diarrhoea or high output ostomy or fistula drainage may be at risk of zinc deficiency because zinc losses through the GI tract may occur. Patients with burns or other wound exudate also lose zinc. Typical oral supplementation is 220 mg zinc sulphate or 50 mg elemental zinc. Prolonged intake of more than 150 mg per day has been associated with copper deficiency. Due to the fact that copper is a component of lysyl oxidase, which initiates the final cross-linking of the collagen, this would have an impact on wound healing. The Committee advises zinc supplementation as per Jackob’s Nutrition Protocol (25-50 mg of elemental zinc for a period of up to 3 months for Stage II and Stage III wounds). The RDA for Vitamin A is 900 RE (μg) per day for adult males and 700 RE (μg) per day for females. The major contributors of Vitamin A to our diets are liver, fish oils, fortified milk, eggs and dark green and orange vegetables such as carrots, spinach, broccoli, and squash.

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Levenson et al. suggested that patients with severe injuries should receive an administration of 25000 IU (4166 RE). To counteract the propensity of antiinflammatory steroids to suppress tissue repair, Hunt advises intravenous administration of 10,000 to 15,000 IU (1666 RE-2500 RE) per day for about a week. Animal sources of Vitamin A (retinol) are about six times more potent than vegetable sources and can be toxic if taken in excess. Because of this, Vitamin A supplements are restricted to carotenes (vegetable sources of Vitamin A). The Committee does not recommend additional supplementation of Vitamin A above and beyond the amount that is contained in a multivitamin/mineral supplement. The Committee emphasises the importance of consulting pharmacists and reviewing clinical practice guidelines when implementing vitamin/mineral/oral nutrition supplements to rule out potential drug-nutrient-nutrient interactions. (e.g., since iron, zinc and copper compete for common transport sites, patients taking a therapeutic dose of 30 mg. Iron should consider taking 15 mg zinc and 2 mg copper supplement).

Nutritional Outcome Monitoring: - The Provincial Skin and Wound Management Committee has developed a Nutritional Outcome Measurement Template - This template uses a combination of objective and subjective indicators such as weight status, appetite, intake,

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affect, mobility status and serum albumin. To track and assess the nutritional progress of patients with wounds, the initial assessment score and the score at a follow-up point should be reviewed and compared.

Protein: -

Water/Liquids: -

Patient Education Pamphlet -

How are all the nutrients for healing wounds obtained? - Follow the recommendations in Eating Well with Canada's Food Guide by selecting foods from ALL four food groups. - Ensure that you consume enough liquids each day. Drink milk, juice, or water along with your meals and snacks. - Talk to a health professional if you have: - An unplanned weight loss - Frequent diarrhoea or vomiting - Loss of appetite - Trouble chewing or swallowing your food - Other health problems like diabetes or high cholesterol - You should talk to your doctor or a dietitian before taking a vitamin/mineral supplement. - Who needs good nutrition? EVERYONE! - Who needs good nutrition for wound healing? YOU DO! - If you have a wound, the nutrients in food and liquids are very important. - These vitamins and minerals are essential for wound healing:

Water, juice, milk, Jell-O, sherbet, ice cream, yoghurt, pudding, soup, popsicles and other liquids except for caffeinated beverages

Zinc: -

Seafood (especially oysters), beef, pork, chicken, milk, legumes (peas, lentils, beans), whole wheat pasta, wheat germ and nuts

Iron: -

Liver, beef, turkey (dark meat), legumes (peas, lentils, beans), baked potato with skin, fortified pasta and cereals

Vitamin A: -

Liver, milk, cheese, broccoli, frozen green peas, spinach, carrots, red peppers, carrots, red peppers, tomato juice, cantaloupe, mango, apricots and peaches

Vitamin C: -

Calories: -

Beef, pork, chicken, turkey, fish, lamb, eggs, liver, dairy products (milk, cheese, yoghurt, pudding), legumes (peas, lentils, beans), seeds and nuts

All foods and drinks have calories, with the exception of water, coffee, tea, and diet drinks.

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Citrus fruits and juices (orange, grapefruit), cranberry juice, strawberries, broccoli, Brussels sprouts, red peppers, tomatoes, potatoes, cauliflower, melons (honeydew, cantaloupe)

In summary

Complex, multi-step processes like haemostasis, inflammation, collagen metabolism, wound contraction, and maturation are all part of the healing process.

The skin makes up to 15-20% of the body's weight, making it the largest and most noticeable organ. It receives 300 ml/minute, or about one-third of the body's blood flow.

Wound healing may occur either primarily, secondary through granulation tissue or by tertiary intention.

The epidermis and dermis are the two layers that make up healthy skin. The subcutaneous tissue, also known as the hypodermis, is a layer of loose connective and fatty tissues that sits beneath the dermis and serves as both a temperature insulator and a barrier against external stimuli.

Delays in the healing process are caused by infections, low oxygen levels, immunological deficiencies, smoking, stress, chronic diseases, hyper-granulation, drugs like steroids, some surgeries, ageing, alcoholism, and nutritional deficiencies.

The normal skin pH is 5.5. PH. A skin pH of 5.5 means that the skin is acidic.

For epithelialization to occur, an atmosphere that is both moist and filled with oxygen is necessary.

The closer something gets to a pH of 1 or a pH of 13, the more acidic or alkaline it becomes, and it has the potential to cause serious burns to the skin

Proper fluid replacement and avoiding dehydration and overhydration are essential for wound healing.

The physiological and anatomical barrier of the skin is significantly affected by ageing.

Despite fluid status fluctuations, serum albumin is still a sensitive and costeffective indication of clinical status alterations such as illness, dehydration and starvation.

Tissue injury can occur either due to environmental, mechanical or chemical factors.

When assessing fluid requirement, patients’ medical conditions such as cardiac status, renal function and exudative losses from open wounds should be taken into consideration

The body's process of replacing damaged tissues with living ones during wound healing is described as a dynamic and complex process in which numerous cellular and matrix components work in concert to restore the integrity of damaged tissue.

Any strategy for wound management will not be effective unless nutritional deficits are addressed.

The type of damage and the degree of tissue loss determine the healing time.

Patients should be evaluated by a nutritionist to make sure their dietary needs are being fulfilled and to decide whether they require nutritional supplements.

Healing takes longer and is more complicated in deep wounds where vasculature has been destroyed compared to superficial wounds where just epithelial tissue is harmed.

The first step in an appropriate feeding plan is the calculation of energy and protein requirements

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Glucose, the simplest form of carbohydrate is the preferred fuel for wound repair. Protein and amino acids are necessary for the synthesis of proteins, including the enzymes involved in the healing process, as well as for cell division. Cell membranes require fatty acids, and shortages may impede the healing of wounds. Vitamins (A, C, K and B complex) and minerals like zinc, iron and copper are essential for wound healing It has also been demonstrated that hospitalised patients' vitamin C level declines during their stay. The iron-binding protein transferrin is routinely utilised to determine a person's nutritional condition. Due to its lower serum pool and 8–10 day half-life, it is more sensitive and selective than albumin. Total lymphocyte count (TLC) has been employed as an oblique indicator of dietary intake and immunological function.

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Pictures Chapter 2

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https://www.google.com/search?q=structure+of+ebiderms&tbm=isch&ved=2ahUKEwj8mI7T_636AhUK 2KQKHRb6DK8Q2cCegQIABAA&oq=structure+of+ebiderms&gs_lcp=CgNpbWcQAzoECAAQEzoICAAQHhAHEBM6C AgAEB4QCBATOgQIABBDOgUIABCABDoKCAAQsQMQgwEQQzoECAAQHjoGCAAQHhAFOg YIABAeEAhQ8whYncUYJzvFGgAcAB4AIABogSIAZEekgEKMC4xOC4zLjUtMZgBAKABAaoBC2d3cy13aXotaW1nsAE AwAEB&sclient=img&ei=M0QvY7yzAYqwkwWW9LP4Cg&bih=657&biw=1366&rlz=1C1FHFK_enE G938EG938#imgrc=3UbfVgDSa8RoBM&imgdii=M8wwLJf2yC1dOM

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Figure Massive necrosis of fingertips. This type of fulminant presentation is often associated with connective tissue diseases, such as rheumatoid arthritis. It generally represents a vasculitis, but coagulopathies may coexist or even be the primary cause. The patient improved considerably with systemic immunosuppressive therapy and wound debridement. She did not lose function of her hand or fingers. This clinical presentation could also be consistent with purpura fulminans (like after varicella infection), leprosy (Lucio’s phenomenon), disseminated intravascular coagulation, frostbite, etc.

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Figure A multistage pressure (decubitus) ulcer. These sacral pressure (decubitus) ulcers are in different stages of development, from nonblanching erythema (stage I), to partial thickness skin loss (stage II), to extension into the subcutaneous tissue (stage III), and bone involvement (stage IV) (Panel A). Some of these ulcers are necrotic and covered by an eschar, while others show some evidence of re-epithelialization (Panel B, inferiorly). The blisters above the necrotic sacral ulcer may be secondary to friction injury. A multistage ulcer also points out the problem of classifying it for both clinical purposes and for clinical trials. A logical solution is to classify according to the worst aspect of it, and therefore as stage IV. Another problem may arise when a pressure ulcer recurs in the same location. Due to the underlying scarring, which may alter its natural size and depth, it becomes unclassifiable.

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Figure A pressure ulcer on the third toe This patient with long-standing diabetes and peripheral neuropathy has had this pressure ulcer from a hammertoe deformity for several months. The ulcer goes through periods of partial healing and enlargement. Ideally, one should remove the surrounding callus and have the patient evaluated for correction of the hammertoe. One should realize that it is important to warn patients that, while debridement is necessary, it will create a much larger ulcer. Topical plateletderived growth factor or bioengineered skin, in addition to protective measures and offloading, will be good therapeutic options here.

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Figure The effect of pressure on blood flow. Pressure causes very substantial decreases in local blood fl ow, and this photograph is a vivid demonstration of this. A glass slide was placed for a few seconds against this elderly woman’s sole. Although not much pressure was applied, blanching of the skin was quite evident. One can extrapolate this finding to the situation encountered by patients with diabetes or other neuropathies. These patients unknowingly place sustained pressure on their feet and, as a consequence, develop prolonged ischemia and necrosis. The technique shown here can be used as a teaching tool to show patients how pressure compromises blood flow.

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Figure Massive necrosis due to pressure. This large sacral ulcer in a nursing home patient needs immediate attention to remove the eschar and drain any possible underlying abscess (Panel A). In Panel B one sees the same ulcer 2 weeks later, after surgical debridement and nursing attention to relieve the pressure. This patient has a good chance to heal. Portions of the wound bed are still becoming necrotic, and will probably require additional surgical debridement. However, removal of the unwanted nonviable tissue could also be achieved with autolytic debridement with a hydrocolloid or hydrogel. We have developed the concept of maintenance debridement, which suggests that debridement (by a number of means) needs to be continued as long as there is nonviable tissue or lack of healing

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Figure A pressure ulcer in a patient with multiple sclerosis. This woman suffered from severe multiple sclerosis and sustained pressure injury to her knee. Her course was also complicated by the development of eosinophilia myalgia syndrome, which was secondary to the ingestion of L-tryptophan and had led to the development of fibrotic skin and subcutaneous tissue, down to the fascia.

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Figure Wound from chemical injury. This patient was injured by exposure to a chemical while at work. These and other wounds on his feet did not heal in spite of a number of therapeutic approaches. Pain was a persistent problem. The patient also had cirrhosis. Although the chemical injury may have been the inciting event, his clinical picture was one of venous insufficiency and ulceration. Generally, he tended to improve with compression therapy.

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Figure Contact dermatitis. Of course, not all skin redness is the result of infection. Here the redness on his neck, within and surrounding the sutures, was due to a localized allergic reaction to topical antibiotics. The tiny and subtle blisters, particularly on the inferior border of the excision, are quite suggestive of a contact dermatitis, rather than cellulitis. Pruritus, rather than pain or tenderness, is another useful clue pointing to a contact sensitivity reaction; cellulitis is generally not itchy. Sometimes, however, the distinction between cellulitis and contact dermatitis is next to impossible. Another point is that the dermatitis is not very well demarcated, thus suggesting that an allergic process is taking place, with inflammatory mediators infiltrating the surrounding skin. With an irritant contact dermatitis, the opposite is true and the rash is better demarcated and has more defined borders.

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Figure Allergic contact dermatitis to mercaptobenzathiol (rubber accelerator). This is an elderly woman with severe venous insufficiency, treated with multilayered compression bandages. The swelling of her legs was improving. However, she developed this severe dermatitis of both legs in areas where the compression bandages were applied, but which could not be easily separated from a case of cellulitis (Panel A). Patch tests with multiple chemicals applied to her back showed a positive reaction to mecaptobenzathiol at 48 hours (Panel B). This chemical is a rubber accelerator that is commonly used in many products. As a result of this allergic component, the application of compression bandages became very difficult. One could opt for short stretch bandages not containing the rubber accelerator.

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Figure Allergic contact dermatitis. This 76–year-old woman with a chronic venous ulcer had an allergic contact dermatitis (Panels A and B) to her foam dressing (proven by patch testing), which was quickly discontinued. She had other allergies to neomycin, gentamycin, and wood tar mix. The patient was treated with systemic corticosteroids, which were tapered over 3–4 weeks. However, there was not much improvement until we used a regimen of clobetasol ointment and a nonadherent dressing with compression. Note the dramatic ulcer size increase occurring during this complication.

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Figure Dermatitis and infection. This is a common combination in patients with venous ulcers, and it is necessary to address both conditions. The wound is debrided and systemic antibiotics are administered. We prefer to treat the dermatitis by avoiding all topical agents, including topical steroids, which could have ingredients that make the dermatitis worse. Gel dressings can be very helpful and soothing, but one must watch out for the development of infection/colonization with Pseudomonas organisms with these types of dressings. On occasion, after treating the infection, we have used systemic corticosteroids for 2–3 weeks to get the dermatitis under control.

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Figure Contact dermatitis and venous disease. This patient was being treated with a zinc-impregnated compression bandage and developed a bullous eruption consistent with contact dermatitis. This occurrence would lead one to use elastic bandages (preferably latex-free) instead of wraps that contain topical agents. It is important to realize that patients with venous disease have a high potential for contact sensitization. Patch testing can be a very important procedure. We have found useful to establish a dedicated clinic to patch test patients to over 100 allergens, including wound dressings.

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Figure Contact dermatitis in venous disease. Patients with venous disease are particularly susceptible to contact dermatitis. Clinicians have always thought that “stasis” dermatitis is an intrinsic component of venous disease. However, we and others have come to the conclusion that “stasis” dermatitis may not be a real entity but the result of sensitization to topical agents, particularly in cold climates that may require the use of emollients. Once patients stop using the topical allergen, it may take months before the dermatitis improves. Unfortunately, and almost invariably, patients or caregivers end up using emollients and other topical agents again in between visits even one application of potential allergens perpetuates the problem and leads to confusion during management.

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Figure Clinical stages of healing in a full-thickness wound allowed to close by secondary intention. Here we have a surgical wound after excision of a squamous cell carcinoma on the back. Panel A shows the appearance of the wound post excision; there are some necrotic areas caused by electrocautery. At 1-week post excision (Panel B), one can observe the fibrinous wound bed with areas of granulation tissue. The granulation tissue has persisted and there is some evidence of epithelialization from the wound’s edges 2 weeks after excision (Panel C). It is to be noted that, for the most part, the process of epithelialization is largely dependent on epidermal migration and less so on the epidermal proliferation. In this photo, there is little or no contraction. At 4 weeks post excision (Panel D), the granulation tissue is well established and the wound bed is almost flush with the surrounding skin. There is increasing epithelialization from the wound margins. Panel E illustrates the appearance of the wound 6 weeks post excision; the process of resurfacing has continued but is now accompanied by the obvious beginning of wound contraction. This is a clear example of the fact that larger wounds may eventually contract because the epidermal resurfacing is not solely dependent on migration and has to rely on dermal events, including extensive extracellular matrix deposition. At 12 weeks post excision (Panel F), the wound has almost completely resurfaced and shows clear evidence of contraction in addition to epidermal migration. Because no skin appendages (hair follicles, sweat glands, etc.) with their reservoir of keratinocytes were left in the wound at surgery, all of the epidermis has to come in from the margins.

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Figure Example of an acute wound with exuberant granulation tissue. This 74-year-old man with a wound on his leg after the removal of a skin cancer was healing by secondary intention and developed exuberant granulation tissue, which is still present 2 months after excision (Panel A). Removal of the exuberant granulation tissue led to healing after 2 or 3 more weeks (Panel B). It is often difficult to determine whether one is dealing with simple exuberant granulation tissue or bacterial colonization; clinical context and bacterial cultures are often required.

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Figure Granulating wound. This excision became infected and a fasciotomy was required. The wound is now left open to heal by secondary intention.

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Figure Basal cell carcinoma of the leg masquerading as a granulating wound. Quite frequently, basal cell carcinoma can present as wounds showing almost optimal granulation tissue (Panel A). Clues to the diagnosis are failure to heal, a rolled border that seems to spill onto the surrounding skin, and intermittent (not connected) areas within the “granulation tissue” that seem to represent epithelium and attempts at healing. The patient was treated with Mohs micrographic surgery to ensure complete removal of the tumor. Panel B shows the wound 2 months after surgery. Complete closure was achieved with secondary intention several months later (Panel C).

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Figure Detection of re-epithelialization/the wrinkle test. The steps outlined above for wound debridement are aimed at removal of necrotic tissue, improve the wound bed, and achieving wound bed preparation with better granulation tissue. Ultimately, however, the goal is to have the wound resurfaced from epithelium at the edges of the wound or from within the wound. During the re-epithelization process, the new epidermis is thin, very fragile, consisting of only 2–3 keratinocyte layers, and probably without the formation of a stratum corneum, which gives it durability. These features of neoepidermis make it difficult to detect. Moreover, the new and fragile epidermis is commonly stripped unknowingly during dressing removal. Several years ago, we noted that the gentle application of a cotton tipped applicator next to the thin epidermis generates wrinkle-like lines. These “wrinkles” are not seen when only granulation tissue is present. We see here a shallow peristomal erosion with some suggestion of complete re-epithelialization (Panel A). A simple test can be done to determine if a wound has re-epithelialized. A sterile cotton-tipped applicator is gently pressed adjacent to the wound to determine whether there are “wrinkles” on the surface. This detects early epidermal resurfacing in a noninvasive way.

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Figure Electrocautery burn. This represents a partial to full-thickness injury. Although the wound bed is still poor and shows what is probably denatured dermal structural proteins and nonviable tissue, there is evidence of epithelialization from the wound’s edges

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Figure Bacteroides melaninogenicus infection. This leg ulcer was found to be heavily colonized with B. melaninogenicus (presently classified in the Prevotella genus). The colonization became evident after the patient had been treated for 6 months with a potent topical corticosteroid (betamethasone valerate). Immunosuppression within the wound may have been the inciting factor. Ulcers colonized with this organism can show fluorescence under ultraviolet light (i.e., Wood’s lamp). The patient began to improve with the application of topical antibiotics, but surgical debridement is generally required to eliminate the organism.

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Figure An infected tumor. This patient had cutaneous T-cell lymphoma. The skin tumor shown here ulcerated and became infected. The photograph shows a purulent wound that appears to be covered by a fi lm-like membrane. Cultures from the wound grew S. aureus. She was treated with IV cephalosporins and the infection was controlled. When ulcerated, tumors frequently become infected.

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Figure Mycobacterial infection and immunosuppression. This patient was immunocompromised from the use of longterm systemic corticosteroids and methotrexate for psoriasis. Initially, the referring clinician thought that this eruption on the patient’s left upper arm looked like a folliculitis and treated him with oral antibiotics. However, the patient did not respond to this therapy and actually developed multiple abscesses on his left upper arm and leg. The photograph mainly shows nodules and ulcers. Culture of tissues from these areas grew M. fortuitum . This microorganism is often associated with subcutaneous and intramuscular injections. Therefore, the infection could have been the result of an injection.

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Figure Heavily colonized wound treated with debridement, antibiotics, and bioengineered skin construct/sequence. The patient was then admitted to the hospital for IV antibiotics and surgical debridement under general anesthesia (Panel C), with immediate postoperative application of a living bi-layered bioengineered skin construct. This was done to achieve proper wound bed preparation and to further stimulate healing. In addition, after we were satisfied that the bacterial colonization was getting under control, the patient was started on oral prednisone to help with the pyoderma gangrenosum. There was rapid improvement within a month. This case illustrates how one needs to remain flexible and open minded, often utilizing multiple concomitant approaches, to achieve proper wound bed preparation in patients with difficult wounds.

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Figure Colonization with S. aureus. This patient had a very large venous leg ulcer with bright red granulation tissue (Panel A) which we correctly assessed to be due to S. aureus colonization. The patient was started on oral antibiotics and silver-releasing dressings (Panel B). We also began compression therapy and pentoxifylline (at high doses of 800 mg 3 times a day). She tolerated the pentoxifylline well, except for some heartburn, which we treated and monitored. She healed in 4 months (Panels C and D).

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CHAPTER

3 Ibrahim Ahmed Elsherbini , Nourhan Mohamed Fahim , Eman Essam Elhofy Faisal Gamal Hemeda

Wound Management The objective is for patients’ normal physiological functions to recover as quickly as possible

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General principles of wound management -

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The majority of healthcare personnel responsible for applying wound dressings are nurses It is the responsibility of all nurses performing clothing changes to give their patients the safest, most efficient, and most comfortable care possible

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Basic principles of asepsis in wound management -

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Asepsis, which refers to the elimination of hazardous bacteria, is the term used to describe the process of preventing the infection of body tissues Dressing change is often referred to as an ‘aseptic technique’ The aseptic approach ensures that anything coming into touch with a wound is sterile and works to stop the spread of infection All dressings and dressing packs are packaged individually, are sterilised during production, and are handled with sterile gloves Effective hand washing is an essential part of the procedure. One of the four guiding principles in the national standards for preventing illness is hand

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According to the recommendations, hands should be thoroughly cleaned by using an alcohol-based hand rub or soap and water to wash them All jewellery, including bracelets, necklaces, and watches, should be taken off Stone-encrusted rings should be taken off

9. Pull open the inner wrapping's four corners using your fingertips alone to cover the trolley's top and create a clean field 10. Prepare any required strapping strips and attach them to the side of the trolley or open bandages and place them on the patient's side. 11. Clean hands thoroughly with an alcohol-based hand rub. 12. Add any other dressings required by opening the outer wrapping and dropping them onto the sterile field without touching the contents. 13. Prepare any strapping strips that may be necessary, attach them to the side of the cart, or position the patient's side with open bandages. 14. Keeping this hand inside the disposable bag, the used dressing can be removed. Then the bag should be inverted so that the dirty dressing is inside the bag. 15. The tape on the bag should then be removed to allow the sticky edge of the bag to be stuck to the edge of the trolley so that it is ready to receive any further waste items. 16. Clean hands thoroughly with an alcohol-based hand rub. 17. Put on the sterile gloves included in the dressing pack, ensuring that only the inner side of the gloves is touched. 18. Clean the wound, if necessary, using either gauze moistened in saline or a syringe filled with saline to remove remnants of the old dressing, dried exudate, loose slough or loose skin scales. 19. Gently dry the skin around the wound with a clean gauze swab. 20. Apply the new dressing and secure it appropriately.

The five-step systematic approach Step 1: Assess the patient, wound and circumstance Before getting any equipment ready, read the wound care strategy. The strategy should detail the following: 1. The kind of injury; 2. How it appeared during the previous assessment. 3. the dressing being applied 4. Adjuvant therapy Step 2: Utilize existing information about the patient The plan of care: 1. If the patient has previously experienced especially painful dressing changes 2. Techniques for reducing discomfort Step 3: Explore relevant current best practice 1. Wash your hands carefully and dry them thoroughly 2. Wear a fresh plastic apron. 3. Clean the trolley with alcohol and allow it to dry for 1 minute 4. Gather all the supplies required for the procedure, such as the dressing pack, gauze swabs, fresh dressing, sterile saline, strapping, or bandages, and set them on the trolley's bottom shelf. 5. Ensure patient privacy by closing the curtains and preparing the patient by placing them in the best position to get clear access to the wound. 6. Carefully remove any appropriate clothing and bedclothes while maintaining the patient's dignity 7. Wash hands with soap and water and dry thoroughly or cleanse thoroughly with an alcohol-based hand rub. 8. Ensuring that the dressing pack is intact and dry, open the outer bag at one end and slide out the contents onto the top shelf of the trolley.

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21. Remove gloves, fold up all remaining items in the sterile field, and place them in the side disposable bag. 22. To rearrange the items on the sterile field, pick up the waste disposable bag from the dressing pack, put your hand inside of it, and use it to move the items around as needed 23. Clean the trolley as before and return it to its usual storage place. 24. Remove the apron and wash your hands thoroughly with soap and water

Principles of wound healing Risk Assessment and Prevention: Determine the patient’s level of risk and implement interventions to prevent the development of pressure ulcers. - Wound Assessment and Documentation Tool: - When a wound is discovered, complete the wound assessment record as per regional policies and procedures - The assessment will provide the clinician with the necessary information to implement interventions. This will help direct the appropriate intervention (e.g. wound bed dry – add moisture; or, if the wound is too wet – absorb exudate). - Wound Assessment Objectives 1. Focusing on the clinical status of the wound is step one. 2. Step two directs the appropriate intervention for the wound. 3. Step three says to re-evaluate and change the plan if the wound status doesn't change within a set timeframe. 4. Steps four through five monitors and evaluate the overall client outcomes (progression or regression) 5. Step five determines the efficacy of the treatment. -

Step 4: Make a clinical decision 1. It is important to assess the wound carefully during the process of wound dressing 2. Before removing the dressing, start by inspecting the exterior to check for any symptoms of exudate leakage. If the dressing is leaking then it may require changing more frequently than stated in the care plan 3. After removal of the old dressing and cleansing of the wound - The wound appearance should be assessed for any changes since the previous assessment - If the appearance differs greatly then a change of plan may be indicated. - If there are signs of infection or a reaction to the dressing, it is advisable to get further advice from the nurse in charge or a doctor.

Assessment Wound assessment can be simplified by dividing the process into several questions: 1. What type of wound is it? 2. Where is it on the body? 3. What does the wound look like? 4. What is the surrounding skin like?

Step 5: Evaluate progress The final step is to record that a dressing change has been undertaken. 1. Details of the wound assessment 2. Any measurements that may have been taken 3. Any changes have been made to the existing wound care plan

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What type of wound is it? - determining the underlying cause or aetiology of the wound - determining whether it calls for further care or has an impact on the plan of care. - A fall or an animal bite, for instance, could have resulted in a skin laceration. - The patient will probably need antibiotics if it was caused by an animal bite due to the high risk of infection. - Antibiotics are typically not indicated if the cause was a minor fall. Where is it on the body? It is important to describe the anatomical position of a wound If a diabetic patient has an ulcer on the sole of the foot, it is most likely to have a different cause than that of an ulcer on the ankle. The position of a wound may affect the dressing choice. For example, although most dressings are easy to retain on a wound on the arm, it can be more problematic if a wound is on the heel or over a joint. Status

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What does the wound look like? Open wounds are wounds such as leg ulcers or pressure ulcers where the skin edges are separated. Closed wounds the skin edges are held together as: surgical wounds where the skin edges are held together with sutures or clips and lacerations where there is no skin loss. Determine the shape and size of a wound The wound bed of open wounds must also be assessed The amount and color of any exudate present is important to determine the status of the wound whether it is healing, static, or has any signs of complications such as infection. Also, the exudate production may be associated with high bacterial growth. The amount of wound exudate may be determined by assessing the interactions with the dressing: Evaluation of dressing: Exudate Interaction

Indicators

Dry

The wound bed is dry: there is no visible moisture and the primary dressing is unmarked: dressing may adhere to the wound NB This may be the environment of choice for ischemic wounds Moist Small amounts of fluids are visible when the dressing is removed; the primary dressing may be lightly marked; dressing frequency change is appropriate for the dressing type NB In many cases, this is the aim of exudate management Wet Small amounts of fluids are visible when the dressing is removed; the primary dressing is extensively marked, but strikethrough is not occurring; dressing frequency change is appropriate for the dressing type Saturated The primary dressing is wet and strikethrough is occurring; dressing change is required more frequently than usual for the dressing type peri-wound skin may be macerated Leaking Dressings are saturated and exudate is escaping from primary and secondary dressing onto clothes or beyond; dressing change is required much more frequently than usual for dressing type

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Record of wound assessment and dressing plan Complete one form for each of the patient’s wounds Patient ID / Name / Ward or sticker Wound site: Type of wound: Complete this section at the initial assessment then weekly or when changes to the wound occur Date and time Grade 1-4 or eschar (for pressure ulcers only) Size (in cms) - Diameter - Length -

Undermining/fistulas

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Photographed/traced Y/N Tissue type (in%) - Necrosis/eschar - Sloughy -

Granulating

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Over granulating

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Others e.g., muscle/bone/adipose Surrounding skin - Oedema - Dry/macerated -

Excoriated

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Blanching/nonblanching - Other e.g., bruising/hematoma Exudate - Color - Odour -

Quantity e.g., heavy/moderate minimum/none - Types e.g., pus/blood/serous Infection - Signs of clinical infection present e.g., heat/pain/erythema/ pus - Swab sent? -

Swab results:

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Treatment aims e.g., manage exudate /deslough/promote granulation/reduce maceration/reduce bacterial loads Comments Print name Signature Designation

Referrals to members of the multidisciplinary team Date and time

Details

Planning Once a full assessment of both the patient and the wound have been completed, it is possible to plan the most appropriate care

Dressing selected – complete at initial assessment and following any changes Date and time Skincare/cleansing regime Primary dressing Secondary dressing Securing mechanism Frequency of dressing change Print name Signature Designation

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Wound redressed – complete this section following each dressing change Date and time Comments Print name Signature Designation

Date and time Comments Print name Signature Designation

The wound treatment plan will be evaluated at least every 2 weeks and when there is a significant change in the wound.

greatest length and the greatest width, marking the points of measurement on the sketch -

Wound assessment by type -

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The duration of the wound, any prior wounds, history of trauma, the characteristics of the wound, underlying medical disorders, smoking, medications, and allergies are all necessary for appropriate wound assessment. Based on how they emerge, wounds can be divided into four groups: The wound site, surrounding skin, and exudate level are additional crucial considerations when choosing a dressing. If a wound is leaking, a dressing must absorb and control the exudate levels, with various degrees of absorption depending on the dressing.

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Measuring wound size

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Wound size progress should be monitored. Methods to measure the wound: -

Draw a small sketch of its shape on the assessment chart and measure the

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Tracing the wound using an appropriate acetate or polythene sheet and a pen. Photographs may also be taken to provide a visual record of a wound at the time of initial assessment and as it progresses The date that the measurement has been undertaken should be recorded so that it can be compared against later measurements incorporated into the wound assessment documentation. A reduction in wound volume by an average of 10–15% per week should be considered a chronic wound and treated accordingly. If the wound does not heal by 50% in 4 weeks, then a more aggressive approach is needed Wound healing society recommends a change of therapy and/or adding adjuvant therapies if the wound size reduction is less than 50% in 4-weektime. This is because the longer the wound remains open, the greater the risk of infection, the deeper spread of

infection, osteomyelitis and ultimately amputation

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What is the surrounding skin like? To consider the status of the skin surrounding the wound. It is an indicator of the state of the wound The skin is red and hot in the presence of infection If there is heavy wound exudate causing the skin to become macerated, it may need special protection N.B. There are several models that can be used to help with wound assessment, but the T.I.M.E. tool is suggested because of its relative simplicity. (This topic is covered in the book's introduction) N.B. Arterial or venous vascular disorders, poor diabetic control, smoking, steroid use and inadequate nutrition, all of which may delay wound healing. Tissue oedema from lymph oedema or chronic organ failure should be controlled, and patients at risk of pressure ulcers should be educated and nursed with a particular focus on pressure relief.

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Peri-wound skincare -

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On previously healthy skin, prolonged exposure to chronic wound exudate will cause maceration and may encourage additional epithelium loss. ‘White maceration’ occurs when there is maceration but little inflammation.

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The peri-wound skin appears white, hard, and swollen. Application of a suitable skin protectant to the peri-wound area can prevent skin damage from wound exudate and reduce the risk of further loss of epithelium. Erythematous maceration- damage may also result in the peri-wound skin being red, inflamed, moist or weeping. Avoid overly adhesive materials, such as some transparent film dressings, which can easily strip or tear the skin in an elderly patient. If adhesive dressings and taping are unavoidable, paint unbroken skin with protective skin sealants to facilitate non-traumatic removal. If an allergic reaction is suspected, have the physician consider the use of mild topical steroids to control associated pruritus and change the dressing protocol. The initial treatment of erythematous maceration is different from that of white maceration. A topical steroid preparation may be prescribed, for a few days only, to reduce any local inflammation present. The topical steroid relieves the symptoms of stinging and soreness within 24 hours and after 2–3 days treatment can continue with regular use of a skin protectant. The addition of a 50% soft white paraffin/50% liquid paraffin mixture (50/50) is required when applying zinc paste on very moist skin and also for removal. A barrier film is widely used as a barrier preparation on peri-ulcer skin and is available as an impregnated sponge on a stick or in a spray.

Types of peri-wound skin lesions

2- Allergic contact dermatitis: -

1- Varicose eczema: -

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The presence of eczema on the skin of the lower leg can complicate the treatment of venous leg ulcers. Care must be taken when applying any dressings and bandages to the skin of a patient with weeping eczema to prevent adhesion to the peri-wound skin. If there is adhesion to the skin the limb should be soaked in warm water prior to the removal of the dressings and bandages to avoid unnecessary pain and trauma to the patient. Adhesive dressings are best avoided on eczematous skin. Varicose eczema is managed with compression therapy to address the underlying venous dysfunction and, if severe, a topical steroid ointment may be prescribed. Topical steroids have an anti-inflammatory effect and decrease cell division in the epidermis. Topical steroids are divided into four groups according to their potency: 1. Mildly potent 2. Moderately potent 3. Potent 4. Very potent The potency of the topical steroid required depends on the severity of eczema. Topical steroids should be applied thinly to the affected area in a downward stroke and not rubbed into the skin. Topical steroids should be used for a few days only and then treatment continued with a simple emollient such as ‘50/50’ (50% white soft paraffin / 50% liquid paraffin).

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It is caused by direct contact with external substances Common in patients with venous leg ulcers. The allergic response is seen clinically as inflamed skin, characterized by erythema, weeping and scaling in the area of direct contact with the responsible agent (allergen) Itchy skin is often a predominant symptom of allergic contact dermatitis. Research studies have shown that it is possible for a patient with a venous leg ulcer to become allergic to any part of their topical treatment including dressings, emollients, creams, bandages and latex gloves of carer. If allergic contact dermatitis is suspected the patient should be referred to a dermatologist for patch testing so the causal agent can be identified and subsequently avoided in future management

3- Dry scaly skin: -

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Dry skin tends to be itchy, and scratching increases the risk of skin breakdown. Dry skin is managed with emollients to prevent water loss and lubricate the skin.

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Emollients form a thin film of oil on the skin, which reduces transepidermal water loss. Apply them to the affected areas. Emollients may be ointment or creams. Ointments are greasy preparations mainly with a paraffin base and have little or no water. They are more occlusive than creams and maintain hydration longer Patients with chronic venous insufficiency who have thick dry skin scale (hyperkeratosis) on their lower legs should have their legs immersed in warm water for 10–20 minutes to soften the scale before applying an emollient A simple emollient, such as ‘50/50’, should be applied regularly, to loosen the scale and keep the skin hydrated) Treatment needs to be frequent and long-term as the skin scale can quickly build up again. Creams are an emulsion of oil in water or water in oil, in semisolid form. When applied to the skin most evaporates due to the high-water content and a thin film of oil is left on the skin’s surface.

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Creams are often more acceptable to patients and carers as they are less greasy than ointment and easily absorbed into the skin. Creams contain preservatives and other additives and are therefore best Avoided in the skin around venous leg ulcers.

4- Skin stripping -

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Skin damage to previously healthy peri-wound skin can occur from repeated application and removal of adhesive dressings and tapes. Eliciting changes to the barrier function and superficial hydration of the skin. This may lead to an inflammatory skin reaction in some patients. The clinical appearance is similar to an allergic reaction. A barrier preparation that leaves a protective film on the skin surface may be applied under adhesive dressings to aid adhesion and prevent trauma on removal.

Wound type

Description

Aims of treatment

Necrotic

Frequently black in colour from dehydration and cell death. Wounds are covered in devitalized tissue Necrotic slough has a highly offensive, often copious, exudate Wounds are covered in a thick or thin layer of yellow/grey tissue. Slough is made of fibrin, leucocytes, serous exudates and protein

To facilitate removal of devitalized tissue. Ischemic wounds are the exception as they are generally kept dry

Wounds have a dark pink or red appearance showing their highly vascular status often with a cobblestone appearance

At this stage, the wounds require a warm, moist environment and minimal disturbance to facilitate healing

Epithelializing These are superficial by nature as they are at the end stage of healing. Epithelial cells migrate from the wound edges or islands in the wound centre, Little or no exudate, the new tissue is quite fragile

To maintain a moist environment and protection of the wound. Wound edges should not dry out as this prevents cell migration

Sloughy

Granulating

To reduce infection risk and prepare the wound bed for healing. This can be through surgical debridement or the use of topical agents

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Wound cleansing -

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Wound cleansing a crucial component of wound care, lowers the bacterial burden, prevents pH extremes from forming, and eliminates contamination. Wherever sensible and practical, wounds should be cleansed by irrigation at each dressing change. The manner of irrigation will vary according to the setting or resources available. Irrigation with a syringe or a bag of sterile saline poured slowly over the wound, or irrigation by the patient while in the shower is advisable. Another form of wound irrigation is the whirlpool. The whirlpool should only be used for wounds that contain slough and necrotic tissue. Once the necrotic tissue is removed, the whirlpool should be discontinued because it can damage granulation tissue. Pressures from 8-15 psi are considered safe and effective for wound cleansing and irrigation. Pressures greater than 15 psi can cause tissue trauma. Pressures of 8-15 psi can be obtained using an 18–20-gauge angiocath on a 30 to 60 cc syringe. A Cochrane systematic review has demonstrated that the use of potable tap water is perfectly adequate and does not increase infection rates. As a readily available hypoallergenic agent, a gentle household soap may be added to tap water, and this has been shown to be equivalent to normal saline and povidone-iodine in the management of wound dehiscence, with the additional benefit of being less harmful to granulation tissue.

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Criteria of cleansers: 1. Should be solvents for the protein exudate present on the wound surface 2. Should assist in managing the bacterial contaminants. 3. The solution needs to be isotonic and neutral in pH Isotonic saline is ideal for wounds that are healing. However, diluted solutions of simple soaps work incredibly well if there is a lot of protein exudate. Commercial wound cleansers contain surface-active agents to improve the removal of wound contaminants. Antiseptics such as Povidone – iodine, hydrogen perioxide, chlorhexidine, Dakins (javex), and acetic acid (vinegar) when used indiscriminately, have been shown to be harmful to fibroblasts. Therefore, frequent use is not advised. It is not necessary for a wound to be "sterile" for it to heal. While most chronic wounds are colonised, only a few of them become an infection

Debridement -

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Wound healing cannot take place until necrotic tissue is removed, or debride when there is deep eschar, purulence, infection or a large area of necrotic tissue. Do not debride if the wound has healthy granulation tissue and no necrotic tissue. Debridement is a basic procedure to help the healing of wounds. Debridement helps in the removal of bacteria, to convert a chronic wound into an acute wound and lots of growth factors are thereby released in the wound. We remove debris, slough, or necrotic tissue in debridement.

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Dead necrotic tissue, hyper granulation tissue, and biofilm in chronic wounds all need to be removed. They lose their ability to produce cytokines. Necrotic tissue, foreign material and bacteria in wound delay wound healing by producing and stimulating the promotion of abnormal metalloproteases such as collagenase and elastase. They prevent chemoattractants, growth factors and mitogens needed for healing. Bacteria inhibit healing by forming a biofilm for their own protection. Black wounds with dry black eschar which requires surgical debridement. Yellow wounds require non-surgical debridement. Red wounds don’t require debridement. This biofilm is an extracellular matrix that irreversibly binds to the wound bed and may cause resistance to therapeutic intervention. The timing of debridement is decided by two factors, ischemia, and infection. In gangrene in an ischemic wound, the timing of revascularization and debridement is critical. In wet gangrene or abscess formation in the ischemic limb, the wound should be debrided immediately, and revascularization should be planned out afterwards. In dry gangrene in absence of infection, the limb should be revascularized first. If any gangrene is present in the ischemic limb, after revascularization, we should closely observe for evidence of new tissue growth underneath the eschar. If there is evidence of new tissue growth, then we should observe the

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gangrene till it falls off or converts into wet gangrene. If there is no evidence of new tissue growth or healing, then it should be operated on. It takes a few days to four weeks for the effect of revascularization of the foot after an endovascular procedure. Surgical debridement is indicated in the presence of restored circulation. Even when tissue perfusion appears adequate revascularization often provides the necessary substrate for wound healing. The effectiveness and postrevascularization improvement in circulation depend on which type of vascular procedure is performed. In surgical bypass, is quicker as compared to endovascular procedures. To avoid debridement of potentially viable tissue during this time, debridement should be delayed. If dry gangrene becomes wet before adequate revascularization, the gangrene should be debrided or operated on.

Types of debridement S. no.

Types

Subtypes

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Mechanical debridement

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Chemical debridement

3 4 5

Biological debridement Surgical debridement Autolytic debridement

1. Wet to dry 2. Hydrotherapy or whirlpool 3. Pulsed lavage 4. Jetforce/Largo/Florida 5. Ultrasonic therapy 1. Enzymes 2. Dakin’s solution 3. Eusole Maggot therapy

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There are several ways to debride a wound. The more common methods are:

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Autolytic debridement is a process whereby the body utilizes its own digestive enzymes to break down necrotic tissue. This is accomplished by keeping wounds moist with hydrogel or moisture-retentive dressings. This allows the body’s enzymes to liquefy devitalized tissue. This method is usually painless but is slower than sharp debridement. It may be used with full-thickness wounds and Stage III and Stage IV pressure ulcers with small to moderate amounts of exudate and necrotic tissue.

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Irrigation: -

Two common methods of wound irrigation are achieved through highpressure irrigation and pulsatile highpressure lavage. A third method is through the use of a whirlpool

Whirlpool or Hydrotherapy:

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Are not a preferred treatment for debridement as it may actually interrupt the healing process. Emerging granulation tissue dehydrates and new vessels are disrupted by the removal of the adherent dry gauze. Because these dressings are applied to the wound wet and taken off-dry, they can be incredibly uncomfortable. This method of removal works by ripping out the slough that gets tangled up in the gauze's weave.

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This is the removal of devitalized tissue from a wound by physical forces rather than chemical (enzymatic), or natural (autolytic) forces. Two types of mechanical debridement include:

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Wet-to-Dry Dressings:

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Wet-to-dry gauze dressings eliminate necrotic tissue and soak up minute quantities of exudate, but because they use a nonselective debridement technique, they may also damage healthy tissue nearby

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Hydrotherapy, or whirlpool, is one of the oldest adjuvant therapies still in use today. Although originally used by physical therapists in the treatment of pain it quickly found a place in wound management. Burns patients, in need of extensive debridement, were immersed in the Hubbard tank, a full-body whirlpool. This quickly led to the development and institution of smaller extremity tanks.

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This makes dressing changes quite painful and psychologically distressing.

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Functions of Whirlpool: -

It helps to remove debris and surface bacteria and contamination It decreases wound pain and fever It helps to remove dressing that has adhered to the wound bed

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Pulsed Lavage or Pusatile Jet Lavage: -

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Pulsed lavage is a type of mechanical hydrotherapy that uses a pressurised, pulsed solution to irrigate and remove necrotic tissue from wounds. It has several advantages over whirlpool therapy, including a quicker recovery period, lower costs, less stress on patients, and a lower risk of crosscontamination. For cleaning and debriding lesions caused by PVD, venous stasis, diabetes, and pressure sores, pulsed lavage is recommended

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Contraindications: -

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It is not to be used near exposed arteries, tendons, nerves, capsules, cavities, fascial wounds recent grafts and actively bleeding wounds. Care should be taken in insensate patients and patients with tunnelling wounds and patients who are on anticoagulants. Pulsed lavage is not suitable for extensive wounds

Precautions and Contraindications: -

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Ultrasonic Therapy for Wound Debridement and Healing: -

because its role is for debridement and wound healing. Ultrasonic therapy uses acoustic energy to remove devitalized tissue from the wound bed and to promote wound healing. It removes particulate matter and reduces bacterial counts. There is hardly any blood loss. Low-Frequency noncontact Airborne Ultrasound Therapy is a known therapeutic modality to treat neuropathic diabetic foot ulcers. It is a known modality of treatment for infected as well as non-infected diabetic foot ulcers. Ultrasonic debridement works by the mechanism known as cavitation. This causes cavitation, fragmentation and erosion of dead tissues. Ultrasonic therapy has some good effects on wound healing. The therapy has no known adverse effects. The therapy is safe and easy to use. It decreases bacterial infection, increases local perfusion, and accelerates wound healing. Electrical stimulation improves the survival of flaps and grafts, speeds up the healing of difficult-to-heal wounds, and even enhances surgical outcomes.

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Ultrasound remains a controversial modality in wound care. This is not a mechanical or surgical modality; it is included in this segment

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It is contraindicated in malignancies, acute infection, ischemic areas and vascular disease and DVT. It should not be used near electronic implants or prostheses and during pregnancy. It should not be applied to the eyes, vaginal region, stomach region, or exposed neural tissue. It should be avoided in case of thrombo-embolic diseases.

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It should be avoided in patients with pacemaker. Precautions should be taken with sensory impairment. Ultrasound should be terminated if there is increased pain.

fibroblasts, resulting in impaired wound healing. Biological: Maggots:

Chemical: -

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Chemical debridement is the removal of necrotic tissue through a chemical process that may include:

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Enzymes: -

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Enzymatic debriding agents work by either directly digesting the components of slough or by dissolving the collagen anchors that attach the avascular tissue to the underlying wound bed. The clinician must follow the manufacturer’s instructions regarding enzymatic debriding agents. Enzymes are not effective in a dry environment. Enzymes must be discontinued once viable tissue is revealed and necrotic tissue is removed.

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Sodium Hypochlorite (Dakin’s Solution): -

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Sodium hypochlorite was originally used as a topical disinfectant. It is nonselective, meaning viable tissue may be removed along with nonviable tissue, and it has cytotoxic properties. Sodium hypochlorite is most appropriately used when there is a large amount of slough on the wound bed and the wound is infected or malodorous. It should be used for a short term, less than ten days. At concentrations of 0.025%, it can remain noncytotoxic and be an effective antimicrobial. At higher concentrations, it may be toxic and pose a risk of damage to

Sterile larvae are introduced into the wound bed. Larvae secrete proteolytic enzymes, including collagenase, that break down the necrotic tissue. Maggot therapy is considered for use in wounds that have not responded to conventional methods of debridement. While there are no reported side effects, care should be taken to avoid healthy skin contact. Some patients may feel a crawling sensation. The clinician can reduce this feeling by confining the larvae to the wound bed. Maggot therapy should not be used in fistula wounds, wounds connected to the body cavity and internal organs, and rapidly advancing tissue necrosis. The sterile larvae secrete proteolytic enzymes including collagenase and that break down necrotic tissue. It is also believed that larvae ingest microorganisms which are then destroyed.

Sharp: -

This is the fastest type of debridement. Examples of sharp debridement are:

Conservative Sharp Wound Debridement: -

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Removal of visible dead tissue above the level of viable tissue. Requires the use of surgical instruments (scissors, forceps, and scalpel). Done by a physician or other qualified health care professional. If done correctly it usually causes the patient minimal pain.

Surgical Sharp Wound Debridement: -

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Performed by a surgeon/physician. Surgical sharp debridement is usually reserved for the removal of massive amounts of tissue or when a patient’s life is in jeopardy from an infectious disease. Penetration extends through viable tissue. Can help turn a chronic wound into an acute wound and thereby stimulate healing. The cost of doing the surgery in the operating room is significant, and using anaesthesia puts the patient at risk.

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Signs and Symptoms of Infection in Chronic Wounds: 1. Abnormal odour – malodorous after cleansing 2. Changes in sensation or pain (type, intensity, duration) 3. Abnormal discharge – purulent, sanguineous 4. Warmth, redness, induration, oedema, discolouration, erythema greater than 2 cm 5. Prolonged inflammatory process; 6. Delayed wound healing; 7. Deterioration of wound site and surrounding tissue, tissue may be friable 8. Poorly or abnormally granulating tissue; may be pale in colour, uneven in growth pattern, have areas of pocketing 9. Bridging of soft tissue and epithelium 10. Increased temperature (may not be present in the elderly)

Laser Debridement: -

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Uses focused beams of light to cauterize, vaporize, or slice through tissue. Two disadvantages may be damage to surrounding healthy tissue and delayed healing.

Identification and elimination of infection -

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rising due to the multiplication of organisms which are now Starting to cause a delay in healing. Critical colonization initiates the body’s immune response locally but not systemically and will affect healing. Infection Refers to the presence of multiplying bacteria that are causing an associated host response. Pathogenic bacteria multiply and invade surrounding tissue resulting in host injury. If untreated, this may lead to systemic infection.

There are four terms that the clinician should know when deciding whether a wound is infected: Contamination: Presence of nonmultiplying bacteria within a wound which accounts for the majority of the microorganisms present on the wound surface. Colonization: Presence of bacteria which are multiplying but are producing no host reaction. This includes skin commensals such as Staphylococcus epidermis and Corynebacterium species, whose presence has been shown to increase the rate of wound healing. Critical Colonization: Refers to a wound in which the bacterial burden is

Diagnosis of Infection: -

To make an accurate diagnosis of infection, there must be an ongoing holistic assessment including: 1. Client status 2. Wound status

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3. Clinical signs and symptoms of infection 4. Microbiologic analysis to confirm the diagnosis and identify the causative agent - One factor alone does not confirm the diagnosis of infection. Swab analysis alone is not conclusive of an infection.

Local Versus Systemic Infection: -

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Identification of Infection: Wound culture – there are several types of wound culture: 1. Tissue Culture: Obtained by taking a tissue biopsy for culture. Considered the gold standard. 2. Aspiration culture: Insertion of a needle into the tissue adjacent to the wound to aspirate the fluid. 3. Swab culture: The collection of tissue fluid on a sterile swab. -

Treating Infections: -

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Guidelines for Swab Culture: -

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Increased heat at the location of the incision, increased pain, increased swelling, increased redness, increased smell, increased drainage, and a change in the colour of the discharge can all be signs of local infection. A systemic infection, on the other hand, is manifested by fever (greater than 38.5o), increased tissue destruction and increased white blood cell count (WBC), and is much more serious than a local infection.

Obtain a wound culture when clinical signs and symptoms of infection are present using the “10-Point” technique. Thoroughly cleanse the wound with sterile water or normal saline. Never take a swab of "old" surface drainage because this will only show what is growing on the surface drainage of the wound, not what is growing in the wound. If the wound is dry, moisten the tip of the swab with sterile normal saline or with the medium found in the base of the culture tube. Use a Zigzag motion. Applying light pressure roll the swab on its side for one full rotation over as much of the wound surface as possible. In particular, sample the part of the wound with the most dramatic signs of infection or the area that is worsening. Be sure to rotate the swab under wound margins and in any tunnelled areas.

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There is significant controversy about the use of topical antibiotic therapy. If it is used, it should be used no more than 7-14 days. Their use may lead to local cell and tissue damage, and systemic toxicity, or it could even lead to the development of contact sensitivity and allergic reactions, superinfections and antibiotic resistance. Systemic antibiotics should only be used when a definitive diagnosis of infection has been established.

Elimination of Dead Space: -

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Dead space refers to a hollow, cavity, or area of tissue destruction underlying intact surface tissue as sinus tract formation. Dead space must be filled, though not overfilled, to promote healing and prevent premature closure of the wound. Wounds heal from the bottom upwards. Dead space provides a fluid medium for bacterial growth.

Absorption of Exudate: -

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Excess exudate at the wound bed can cause maceration and tissue damage. It can pool and promote bacterial growth.

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Excess exudate is detrimental to wound healing and requires removal to achieve the optimal wound environment for healing. Change dressing before break-through of drainage. Choose an absorbent dressing and change the dressing before it becomes entirely saturated.

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Promotion of Moist Wound Healing: -

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Maintaining a moist wound environment facilitates the woundhealing process. Benefits associated with moist healing include: Increased rate of re-epithelialization – Wound healing is facilitated by a relatively hypoxic wound environment. Hydrocolloid dressings are capable of enhancing the process of angiogenesis. Moist wound healing helps to prevent crust formation, which leads to a faster epithelial migration across the moist wound bed. Bacterial barrier – occlusive dressings act as a barrier to keep environmental microorganisms from coming into contact with the wound. Decreased pain – local wound pain is significantly reduced in occluded wounds due to hydration of the wound by the dressing that insulates and protects nerve endings. Moist wound healing can help with the painless debridement of wounds. Enhanced autolytic debridement

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Protection of the Healing Wound: -

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Promotion of Thermal Insulation: -

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This impairment can increase the risk of infection because it causes vasoconstriction and increases haemoglobin’s affinity for oxygen. Both these processes decrease the availability of oxygen to the phagocytes. The consequence of hypothermia on phagocytes includes decreased phagocytic activity and decreased production of reactive oxygen products. Normal body temperature for optimal cellular function in humans is 36.4oC to 37.2oC. Above or below this range, the cellular reaction or process may be impaired or shut down. The wound temperature stays warmer when a dressing is more occlusive. Different moisture vapour transmission rates (MVTRs) apply to different moisture-retentive dressings

Wound healing is accelerated when the wound bed is kept warm at body temperature, therefore, frequent dressing changes should be avoided when possible. Local hypothermia can impair the healing process and the immune response.

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Mechanical injury to the wound may occur because of shear, pressure or friction forces. Interventions to prevent reoccurrence Proper positioning and transferring techniques Pressure redistribution support surfaces to reduce or eliminate pressure Healed venous leg ulcers require compression hosiery for life Frequent educational updates for the client with diabetes with attention to: - Proper footwear. - Proper foot care. - Proper nail cutting. - Tight control of blood glucose, blood pressure, blood cholesterol and triglycerides. - Education to all clients and their caregivers on the prevention of reoccurrence.

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Pain management

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Patients may be unable to comply with treatment such as compression bandaging, due to pain. A wound that fails to heal is at risk of becoming infected, leading to further delayed healing and further associated depression so that a vicious circle of pain and non-healing can occur. Successful interventions to lessen pain will not only improve the quality of life but also improve the overall health of the patient and in many cases expedite wound healing.

Physiology of normal pain -

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Wound pain may be caused by the initial trauma that resulted in the wound or persistent trauma to the wound bed, or it may be due to the underlying disease process that caused the wound. It may be also associated with interventions such as debridement (removal of dead tissue from the wound bed) or dressing changes. Continuous pain has an obvious negative impact on quality of life and affect clinical outcomes and impairs wound healing. Patients in pain experience a variety of physiological changes that can be detrimental to their health such as increased blood pressure, altered blood gases, delayed gastric emptying or urinary retention. Psychological stress brought on by intense pain has been found to have a negative impact on wound healing. Emotions such as fear, anger, and depression, can influence pain perception. In addition, healing may be impaired by sleep deprivation, heightened stress levels, immobility and increased inflammation caused by pain.

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The body’s nervous system specifically dedicated to detecting pain is known as the nociceptive system. It consists of: - Nociceptors (sensation): these are sensory receptors in the skin that are sensitive to noxious or painful stimuli or to stimuli which would become painful if prolonged. - Neural pathways (transmission): these consist of A and C fibres that send nerve impulses to the central nervous system (spinal cord and brain). - Processing areas (perception): these are neural areas in the brain that process incoming impulses to generate an awareness of the painful stimuli via the sensation of pain and interpret pain, identifying its cause and effect on the body. - Emotional response to pain is generated in the brain.

Gate theory and dimensions of pain -

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In addition to being a physiological reaction to tissue injury, pain can also be perceived differently depending on emotion and experience.

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In 1965 Ronald Melzack (a psychologist) and Patrick Wall (an anatomist) worked together and presented the ‘gate control theory of pain (Melzack & Wall, 1965): According to this hypothesis, a spinal cord gate metaphorically controls the flow of harmful information that travels to the brain. If the gate is open, noxious information can reach the brain to generate the sensation of pain. If the gate is closed noxious information cannot reach the brain and the sensation of pain does not result. Transmission through the gate is influenced by descending impulses from higher up in the nervous system as well as other competing stimuli in addition to the peripheral stimulus's intensity. This explains why distraction techniques can help reduce pain perception. Further work in this area suggested there are distinct dimensions of pain perception (Melzack & Wall, 1988): Sensory dimension: relates to the intensity, location, and quality of pain. Information is provided by the nociceptive system and is then relayed to and from the cortex of the brain. Affective dimension: relates to the emotional aspects of pain. Information is provided by the nociceptive system and is modified in the brain. For example, a very frightened patient may experience higher levels of pain.

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Chronic pain (persistent pain) -

Chronic pain is pain associated with an injury which is not resolved within an expected period of time, for example, pain associated with a chronic wound or an ongoing disease process such as cancer or an ischemic limb. - It may manifest itself as recurrent episodes of acute pain. - Persistent pain may be associated with ongoing tissue damage as in chronic wounds and can be divided into two categories: - Useful pain: this acts as a warning signal that something is going wrong in the wound, i.e., infection, ischemia, injury or inflammation. Increased pain levels post-surgery may also be a symptom of bleeding into the tissues. - Useless pain: this is where the nociceptive system has become sensitized, damaged, and dysfunctional (neuropathic pain). Neuropathic pain can be characterized by unusual symptoms such as numbness, shooting pains, electrical sensations and deep aching. - In addition, the signs of hyperalgesia or allodynia may be present. An understanding of these types of abnormal pain sensations will have an

Duration of pain Acute pain -

Acute pain may also signify that there is a deterioration in the wound, due to infection, ischemia, injury (this may be iatrogenic, i.e., caused by the practitioner) or inflammation, which may need prompt intervention. Pain should be regarded as the fifth vital sign (along with temperature, pulse, blood pressure, and respiration rate), and its presence should never be ignored either in an acute surgical wound or in a chronic wound.

The definition of acute pain is "pain of brief duration and little consequence." It typically has a causal relationship to injury and disease.

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impact on a nurse’s appreciation of a patient’s pain during dressing change. In hyperalgesia pain sensation is exaggerated either within the wound or in the healthy tissue surrounding the wound. This type of pain may cause a patient to cry out in pain when lightly touched during dressing change. Allodynia is the perception of nonnoxious stimuli, such as mild touch, as painful in or near the wound. In contrast to nociceptive pain, neuropathic pain has no utility in terms of preventing the wound from additional damage.

Key factors in the assessment -

1. 2. 3. 4.

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Assessment -

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‘To understand and adequately treat pain we have to be able to measure it. Establishing the cause of the pain is of vital importance for identifying the cause of the symptoms and suggesting a course of management. In the case of a surgical wound increase in pain in conjunction with raised temperature and pulse rate may suggest infection. In a chronic wound that becomes infected there may be little in the way of clinical signs and the only clue may be pain or increased pain. Leg ulcer pain is particularly complicated, and it frequently correlates with the cause of the wound. Pain assessment should be incorporated into every leg ulcer assessment and should be carried out by a suitably trained nurse. It may be that interventions such as dressing changes or debridement are either exacerbating or causing the pain. If this is the case, then pain prevention strategies should be clearly identified while planning care.

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Six key factors are commonly identified as the essentials of all pain assessment: Location: in the wound, around the wound, referred elsewhere. Description: ask the patient to describe pain in their own words. Duration: how long has the pain been present? Intensity: how bad is the pain? A formal assessment tool (see below) may be used. Influencing factors: factors that either help relieve pain, for example, position, or movement, or aggravate the pain, for example dressing change. Previous treatment: what has or has not worked. What analgesia is the patient taking and has it made any difference? Have any dressings made the pain better/worse?

Pain Scales -

The most crucial query to ask is, "Are you in pain and, if so, where does it hurt?" Having confirmed that the patient is in pain, a suitable pain scale can be selected to assess severity. - Commonly used pain scales are: - Verbal Rating Scale (VRS): this scale consists of a range of words from no pain to unbearable pain. The words to describe the pain may be predetermined or the patient’s own words may be used. - Numerical Scale: patients are asked to describe their pain in numbers rather than words. For example, from 0 = no pain to 10 = the worst possible pain.

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Visual Analogue Scale (VAS): patients are asked to indicate the intensity of their pain by placing a mark on a line with no pain at one end and unbearable pain at the other. is an example of a combination of a VRS and VAS scale. Faces Rating Scale: This scale represents the intensity of pain using faces from a continuum from smiling to crying. These can be useful for children or adults who have difficulty conceptualizing pain as a number or a word. These pain scales can be used to evaluate a patient's general level of discomfort or to evaluate pain during an intervention, such as a dressing change or ongoing evaluation.

and trauma on dressing removal and should be avoided. - Some modern adhesive-backed dressings may cause trauma to fragile skin and sometimes to the wound bed. - Soft silicone dressings, on the other hand, can be safely left in place for up to 7 days because they do not stick to the skin around the wound or the wound bed. Tissue injury -

Impact of exudate

Managing wound-related pain

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Pain at dressing changes -

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Tissue injury may occur if the dressing has been badly positioned or a bandage has not been applied correctly and consequently is cutting into the skin and causing unnecessary pain and distress to the patient.

Pain at dressing changes can be difficult to avoid. Building a positive rapport with patients is crucial because they will perceive pain differently if they have had a bad experience in the past. Reassurance and creating a relaxed atmosphere are also important. The patient may prefer to remove their own dressing. Distraction techniques such as having someone else there to talk to the patient may be helpful. In severe cases systemic analgesia may be administered prior to the procedure or gas and oxygen may be given. Analgesic lozenges, although expensive, are very effective and userfriendly. However, in most cases selection of a non-adherent dressing is sufficient to allow for pain-free dressing changes. Traditional dressings such as gauze and paraffin gauze often cause pain

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Maceration and wound extension are likely to happen and cause discomfort if a moist dressing is placed on a wound that is heavily leaking. Conversely a dry dressing on a dry wound will cause tissue adherence and pain. Maintaining the ideal moisture balance at the wound interface through the careful selection of dressings is essential for improving both patient comfort and wound healing.

Infection -

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The signs of infection are heat, redness, pain, and swelling. Increasing pain, along with odour and increased exudate, is frequently the first indication of elevated bacterial loads in a wound bed. Different types of dressings are already available for treating wounds that have a high bacterial colonisation rate. Cadexomer iodine dressings have been available for many years, and more

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recently honey and silver dressings have become popular. They all have a role, but unfortunately many patients find the honey and iodine dressings very painful after application.

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Pain at debridement -

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Sharp debridement should only be undertaken by a suitably qualified practitioner. The nursing assistant should make sure the patient is not in pain during the operation. Application of topical local anaesthetic can be effective. Patients must be reassured that the procedure will stop if they so request. Persistent pain Persistent pain is continual ongoing pain. There are dressings now available that have been shown to relieve pain in many patients. In many cases pain is not controllable by dressings alone and appropriate analgesia should be prescribed. It should be kept in mind that any drug has the potential to cause unpleasant side effects in a patient, and if this happens, alternative medication should be looked into.

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Appropriate dressing choice -

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An ideal dressing physically and microbiologically protects a wound; is non-toxic and nonallergenic; and maintains wound humidity while removing necrotic material and promoting gas exchange, granulation and reepithelialization. Healthcare professionals should choose a dressing that best fits these criteria while being affordable and non-traumatic.

Considered antibiotic prescription -

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Timely dressing change -

times a week, with 20% of wounds requiring daily dressing changing. Healthcare providers should use analgesics, adhesive remover, and soak dressings before removing them to prevent patients from experiencing pain when changing dressings. The skin should not be irritated by dressing adhesive, and photos can be taken to track a wound's development. If exudate is difficult to control, a total negative pressure dressing may need to be considered.

The ideal frequency of dressing changes is ultimately decided by the available resources, the characteristics of the dressings used, the patient's comfort, and variables such as the amount of wound exudate, anatomical position, and colonising organism. Studies show that on average, wound dressings are changed 3.5

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Careful antibiotic use reduces the risk of drug-resistant healthcare-related infections. Topical and systemic antibiotics should only be prescribed where clear evidence of infection is present (increased pain or wound discharge, spreading erythema, pyrexia, etc.) and only once appropriate wound swabs have been examined. When prescribed, antibiotics should be used for the shortest possible period and targeted to the likely causative organism, For chronic wounds where the presence of a bacterial biofilm is

suspected wound cleansing with an antimicrobial irrigation solution such as Prontosan is recommended.

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There are numerous methods for the classification of wounds.

Classification of wounds Wound classification Aetiology

Rank Wakefield classification system

The Skin duration of integrity wound healing

Wound depth

Morphological The degree of characteristics contamination

Severity

Surgical wound Wound caused by a surgical procedure

Tidy wounds Wounds cause by sharp instruments and do not contain devitalized tissue e.g., surgical incisions, knife wounds, glass cut

Acute wounds Wounds which heal in an anticipated time frame (immediately or in few weeks) e.g., wounds resulting from traumas or operative surgery

Open wounds Wounds in which the skin has been compromised and underlying tissue is exposed e.g., incisions, lacerations, amputations, punctures, abrasions, etc.

Superficial wounds Wounds in which only the epidermis is affected This type of wound does not bleed and usually heals in a couple of days e.g., abrasions and blisters

Bruises/ contusions Wounds in which only the epidermis is affected This type of wound causes trauma which damages tissue under the skin without breaking it

Clean wounds Wounds in which no inflammation is encountered and the respiratory, alimentary and genital tract are not entered

Penetrating wounds Wounds caused by penetrating trauma

Untidy wounds Wounds caused by crashing vascular injury, burns and are commonly associated with fractures

Chronic wounds Wounds which do not heal in an anticipated time frame and can reoccur Duration >4w to 3m Wounds which occur as result of an underlying condition such as pressure on tissues from an extended time and poor circulation e.g., pressure and diabetic foot ulcers

Closed wounds Wounds in which the skin has not but underlying tissues have been impaired e.g., contusions, bruises, hematomas, tumours, crushing injuries

Partial thickness Wounds in which the epidermis and a part of dermis are affected This type of wound does not bleed if left uncovered a blood clot will cover it and scar will form

Hematomas This is a type of closed wound caused by damage to a blood vessel which results in blood collection under the skin

Clean contaminated wounds Wounds in which the respiratory, alimentary, genital and urinary tract is entered under controlled conditions and without unusual contamination

Simple wounds Wounds in which the skin integrity is traumatized without loss or destruction of the tissue and the presence of a foreign object in the wound field Complex wounds Wounds in which the tissue is lost because of crash, burn or foreign body into the wound

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Blunt wounds Wounds caused by blunt trauma

Full thickness Wounds in which both the epidermis and dermis are affected also underlying tissues (fatty tissues, bones, muscles, tendons) may be affected This type of wound cannot be sutured as the healing process will generate new tissues to fill the wound followed by the regeneration of the epidermis

Burn wounds Wounds caused by burn injuries First degree Outer layer of the skin is affected Second degree Superficial or deep layer of the skin is affected Third degree Subcutaneous tissue is affected Forth degree Full thickness, extended to muscles and bones

Crush wounds Wounds caused by a great amount of force applied over time This type of wounds occurs when an object falls onto a person splitting the skin and tearing underlying tissues

Contaminated wounds Wounds which are fresh, open or accidental with major breaks in sterile technique or spillage from git non-purulent inflammation are encountered

Abrasion Wounds caused by a shearing injury of the skin

Infected wounds Wounds which are old, with retained traumatized tissues and existing clinical infection

Penetrated wounds

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According to the duration of wound healing Acute wounds Heal within a relatively short time frame

Chronic wounds Slow to heal

Heal without complication

Complications due to various underlying problems and pathological conditions

Normal inflammatory response Exudate production decrease as wound heals

Prolonged inflammatory response Increased and prolonged production of wound exudate

Acute wound fluid stimulates cell proliferation

Chronic wound fluid has sustained high levels of tissue-destructive enzymes

Decrease in protease activity in AWF as wound heals

Increased protease activity in CWF contributes to degradation of cell adhesion proteins required for tissue repair

Examples (surgical, traumatic, burn)

Examples (pressure ulcers, leg ulcers, diabetic foot ulcers, malignant fungating wounds)

Acute wounds: -

1. Surgical wounds: - Surgical wounds are, obviously, a result of a surgical procedure. - Classification of surgical wounds to measure infection rate:

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Classification Criteria

Risk of SSI in cattle

Clean

10.1 per cent

Clean contaminated

Contaminated

Dirty

Non-traumatic elective procedure where surgical site is not inflamed or contaminated No break-in aseptic technique Elective opening of respiratory gastrointestinal, biliary or genitourinary tract with minimal spillage Minor break in aseptic technique Gross contamination is present at eh surgical site without active infection including spillage of GI tract, incision into acute nonpurulent inflammation Major break in aseptic technique Active infection at the surgical site (purulent exudate is encountered) Surgery of traumatic wound with retained foreign bodies or faecal contamination Ruptured viscus

15.4 per cent

26.7 per cent

50 per cent

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Surgical wounds can vary greatly in size and can occur on any part of the body. Most surgical wounds have the skin edges held together by sutures, clips or tape. A smaller number may be left open to heal from the bottom up or for suturing a few days later. Methods of closure: - Depending on the location of the wound and the surgeon's preference, the layers of tissue are typically sutured, and the borders of the skin are pulled together and approximated by sutures, clips, staples, or tape. - Depending on the position of the wound, sutures, also known as stitches, are removed between 7 and 14 days after surgery. They can be created from a range of materials such as nylon and silk. - Clips and staples are made of metal and require special applicators for applying and removing them. Generally removed between 5 and 7 days after surgery.

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There are also small, pre-cut tapes designed specifically to hold skin margins together. You can leave the tapes in place for 7–14 days. This is called healing by secondary intention, whereas healing with the skin edges closed is called healing by primary intention. Due to the high danger of infection or the requirement to allow drainage from the wound, it is not appropriate to close the skin in this manner for various surgeries. In some cases, the incision is closed from the inside out while leaving the outside tissue layers open to heal. In order to prevent the wound from closing too quickly, the cavity is filled with a dressing material such as alginate. These wounds are usually associated with infection, for example, an abscess. Although it is vital to measure the number of surgical wounds for epidemiological research since they are deliberate wounds caused by problemsolving procedures, the number of operations is only counted in relation to government targets and planning for future care delivery. However, the incidence of surgical wound infection is monitored as this is a complication that can have serious implications for the patient as well as costing a great deal to treat. When monitoring the rate of infection in surgical wounds it is usual to divide wounds into different It demonstrated that how the potential for infection varies and why prophylactic antibiotics may be given routinely to prevent infection in high-risk operations such as following traumatic injury.

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Most surgical wounds heal, without incident, by primary intention and will epithelialize Within 48 hours, which seals the wound. There is insufficient evidence to conclude that a dressing is necessary after this point (However, dressings provide protection for the wound against rubbing by clothing and improve patient comfort). An ideal dressing for a surgical wound should be affordable, conformable, low-adherent, semi-permeable, and absorbent. Probably the most common type of dressing used is an island dressing, which meets all the above criteria. Other types of dressing in regular use are films, thin hydrocolloids and foams. Film dressings offer the advantage that the wound may be seen without having to remove the dressing, but they lack absorbency unless they expressly include an absorbent pad

Complications of surgical wound: 1. 2. 3. 4. 5. 6. 7.

Hemorrhage Wound infection Wound dehiscence Hemorrhage Evisceration Hematoma Poorly approximated incision line

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The most common complications are haemorrhage, infection or breakdown of the suture line, known as dehiscence. Hemorrhage can occur during the operation or in the postoperative period (may be due to uncontrolled bleeding during the operation, a slipped suture around a blood vessel or, if it occurs late in the postoperative period, infection).

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The bleeding needs to be controlled and may require further surgery. If excessive, the patient may require a blood transfusion. Infection can occur in around 10% of surgical wounds. It may be caused by several different factors, but the poor surgical technique is the most common. Some surgical procedures carry a greater risk of infection than others. For instance, the risk of infection is substantially higher following surgery to repair a perforated appendix than following varicose vein surgery. Patients typically receive antibiotic prophylaxis when there is a recognized risk of infection. Wound dehiscence may occur along part or all of a suture line There are a variety of reasons for the dehiscence, such as infection, poor suturing technique or the sutures being removed too soon. Dehiscence along a portion of a suture line is typically left exposed to allow granulation to repair the area. Depending on the size and depth of the incision, these wounds can be quite sloughy with a moderate to substantial quantity of exudate. Appropriate dressings may be alginates or hydrofibre dressings for deep wounds with heavy exudate or an amorphous hydrogel for shallower wounds. A used dressing won't adhere to the wound and will keep the exudate from the wound wet on the wound surface, promoting the migration of epithelial cells. A wide range of dressings could be used, for example, thin foams, films, hydrogels, hydrocolloids, and siliconebased dressings. Selection should be

based on the position of the wound and the status of the surrounding skin. Monitoring progress: -

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Nurses have a responsibility to monitor surgical wounds closely for any indication of complications. Ideally, this should be undertaken at least every 4 hours for the first 12 hours after surgery and then daily until the skin closures are removed. As patients are often discharged after a few days this is not always possible. Patients should be given written and verbal advice on the possible indicators of complications and the actions to be taken should they occur.

Patient Management: -

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A key component of nursing care is reducing patients' anxiety by making sure they have clear information about the entire procedure so they know what to expect. Every patient is entitled to effective postoperative pain management and patients require assessment and appropriate analgesia. Some patients will require specific care because of pre-existing conditions such as diabetes. Others will need to adhere to a schedule of care according to their type of operation. For instance, patients having orthopaedic surgery might need to restrict their range of motion, but those having gastrointestinal surgery won't be

able to resume their normal diet right away

Principal of closed surgical wound care -

Surgical Site Infection (SSI): -

Surgical Site Infections are defined as occurring within 30 days of the operative procedure. If an implant is used, such as a mesh, the time for the SSI may extend to one year.

Types of surgical site infection:

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1. Superficial infection: includes the skin or subcutaneous tissue of the incision. 2. Deep infection: involves the deep soft tissue of the incision, i.e., fascial and muscle layers. 3. Organ/space infection: involves any part of the organs or spaces that was manipulated during surgery other than the skin. Bacterial count and host resistance are the two major factors determining the development of post-surgical wound infection. Site of surgical incision: Incisions that cut across Langer’s lines are not ideal for wound healing although they may be necessary to gain access to the site of operation. Length of pre-operative stay: the longer the hospital stays before surgery the higher the risk of wound infection. The patient's skin may become colonized with bacteria from the hospital environment; admission to the hospital may reduce the patient's general physical fitness. Pre-operative bathing and showering are linked to an increase in skin organisms, probably by the spread of germs from sites with high

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colonisation, like the axilla and perineum. - Pre-operative bathing and showering: Using non-medicated soap is linked to an increase in skin organisms. If feasible, take a shower the night before surgery. Hair removal: Routine hair removal before surgery is not essential. Depilatory creams are advocated by some, but problems have been reported. The incidence of sensitivity reactions in these studies ranged from 1.0%-7.7%, necessitating a delay in surgery. The greater the time lag between shaving and surgery; the more time bacteria have to multiply. Length of operation: An increased incidence of Infection with longer operations, approximately doubling with every hour of the procedure. Skin preparation of the operation site: Antiseptic skin preparation aims to remove transient and pathogenic organisms on the skin surface and reduce the resident flora to a low level. Choice of suture: Since sutures are foreign bodies and as such can set up an inflammatory response, it is important they are removed as soon as the wound is strong enough to remain intact without their support. Post-operative care: Involves a very small risk of introducing bacteria into the wound. It depends on how quickly fibrinogen is converted to insoluble fibrin as well as the speed at which the fibrin contracts to form a firmer structure. Wound dressings: The purpose of dressings applied in theatre is to absorb exudate and protect the wound from exogenous contamination until the incision line is sealed. It prevents sutures from catching on clothing or bedding. Where the level of exudate is low, film dressings have been used in

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surgical wounds without an increase in infection rate. Wound drainage: Drains can act as bacterial conduits through which skin contaminants can gain access to deep layers of the wound, although this risk is greatly reduced if a closed system is used. Despite using a closed system, the risk can still be significant if there is prolonged use and frequent emptying of the drain. The solution lies in the prompt removal of the drain when the benefit of hematoma prevention is outweighed by the risk of wound contamination. It is safer in terms of tissue trauma to release the vacuum prior to removing the drain. Use of antiseptics: clinical studies assessing are inconclusive and comparison of the results is difficult as different preparations are used. The effects of long-term use are uncertain. Alcohol-based solutions of antiseptics should not be used for wound care because of the strong cytotoxic effect of alcohol. Washing and bathing after surgery: There is no increased risk of infection when sutured wounds are washed with soap and water from the first postoperative day. A shower may be preferable to a bath following surgery as there is less possibility of crossinfection from a previous user

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animal, or human bites and finger-tip injuries. The more serious of these injuries require treatment in an accident and emergency department (A&E).

Patient history: -

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2. Traumatic - The most common minor traumatic injuries are cuts, abrasions and lacerations. - Traumatic wounds are caused by accidental or malicious injury. - Major traumatic wounds require surgery and so become translated into surgical wounds. - Minor traumatic injury includes cuts, abrasions, lacerations, skin tears,

Find out when and how the injury occurred, taking into account that some injuries may not be accidental. Accident and emergency departments have policies for dealing with suspected non-accidental injuries, particularly in children and older people: Make a record of any first-aid treatment that has already been applied to the wound. Determine the patient’s tetanus immunization status and whether booster immunization is required. Determine if the patient has any allergies, especially to wound care items such as adhesive tapes. Ascertain the patient's social situation, whether the patient is a single person or not, and whether support is accessible if needed. If the wound is likely to be disfiguring, then there may be psychological issues to address, either immediately or at a later stage. Determining the patient's level of discomfort is crucial since it could be essential to administer analgesia before beginning any treatment.

Wound assessment: -

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- Make sure the full extent of any traumatic damage is visible, and examine the wound to see how much bleeding has occurred; keep in mind that head wounds flow profusely. Any tissue loss should be identified – this involves assessing whether any of the skin’s epidermis has retracted away

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from the dermis, or if there is a complete loss of the epidermis or deeper layers of tissue. - Check to see if the damaged part has lost any sensation or function. Check to see if a patient can move and bend a finger that has a deep cut, for instance. When a hand is injured, check whether it is the dominant hand or not. Although medical assessment and intervention may be required in many situations, skilled nurses may manage some of the minor injuries.

2. Laceration: - Are penetrating wounds with a jagged edge. - Caused by sharp objects or blunt instruments that cause tearing of skin and possibly the tissue below. - commonest position below the knee (pretibial lacerations) - Severe lacerations, where there is a large hematoma and possibly necrosis of the skin flap or where there is a major de-gloving injury, require surgery. - Simple lacerations, even with a small hematoma or skin-edge necrosis, can be managed conservatively. - Any hematoma should be evacuated, and any necrosis trimmed, after which the skin edges can be brought together, and adhesive strips applied. - Pre-tibial lacerations should have a supportive bandage applied from toe to knee.

Wound Cleansing: -

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Abrasions often feel very sore and may benefit from being covered with a film dressing, thin hydrocolloid or adhesive foam dressing.

Before applying any form of treatment, it is essential to ensure that the wound has been thoroughly cleaned to remove any foreign bodies, such as grit or embedded clothing, from the wound. By their very nature, traumatic wounds are likely to be heavily contaminated with bacteria and so at great risk of infection, especially if the injury occurred some hours previously. Cleansing is best achieved by using either normal saline or tap water.

Examples of traumatic wounds:

3. Cuts: - Cuts are caused by a sharp instrument without tissue loss. - Treatment aims to control any bleeding and to hold the skin edges together to allow healing. - Depending on the position and depth of the cut, it can be managed in a variety of ways, such as sutures, adhesive strips, or tissue adhesives. - Sutures should be used on cuts over joints or on cuts on the hand. - Their use takes considerable skill to prevent scarring, especially when used to treat facial cuts. - Adhesive strips can be useful if the patient has fragile skin which might

1. Abrasion: - Can be described as a superficial injury where the skin surface is rubbed or torn - This type of injury most commonly occurs from falling onto a rough or gravelled surface. - Occur due to trauma, as in the case of “Road Rush” or from elective procedures such as derma abrasion. These wounds initially produce copious amounts of exudate composed of blood and serous fluid. - Traumatic abrasions are frequently contaminated with physical debris and if left unattended may lead to infection.

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4. -

tear if sutures are applied. However, they should not be used over joints as they are likely to pull away from the skin if stretched. Tissue adhesives (or glues) can be very useful, especially for treating children as they can be applied quickly and painlessly. They can be very useful in treating cuts on the head as only a very small area of hair needs to be shaved off compared with the amount needing to be shaved off to apply sutures. Skin tear: Caused by friction and/or shearing forces Occur in people with thin fragile skin (elderly) Mostly occur on the arms or legs

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3. 1. 2. 3. 4.

1. Pressure ulcer: - Pressure ulcers have been defined as an area of localized damage to the skin and underlying tissues caused by pressure, shear, friction or a combination of these. - They are also known as pressure ulcers, bed sores or decubitus ulcers. They are ulcers, or wounds formed when skin is subjected to unrelenting pressure and shear (movement between a bed and skin). - These physical factors induce tissue necrosis and ulceration. - “Pressure” is a perpendicular load or force exerted on a unit of bodily area. In a sitting position, the deep fascia of the body moves in a downwards direction with respect to the skeleton, while at the same time the skin that is in contact with a bed remains stationary, thus creating “shear”. - “Friction” is the force produced by two surfaces moving across each other. Pressure, shear and friction are implicated in the pathogenesis of decubitus ulcers (also called here” pressure sores”)

6. fingertip injuries: - It occurs in young children who get their fingers crushed in doors. Aftercare

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Burn injury: There are four causes of burns Thermal (fire or hot fluid) Electrical Chemical (spillage of corrosive) Radiation

Chronic wounds:

5. Animal and human bites: - Cause bruises, cuts, lacerations or puncture wounds

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maybe day 14 in a hospital clinic or general practitioner's office. The majority of wounds will heal without complication, but there is a risk of infection in these wounds. Patients should be advised to seek medical assistance if the wound becomes swollen and inflamed or the level of pain suddenly increases.

Some patients may need assistance at home, especially if they have hand wounds, as performing routine, everyday tasks may be challenging If this is the case, they should be encouraged to seek help from family or friends. Patients should also be encouraged to mobilize as much as possible. If the injury affects a limb or digit, it is helpful to elevate the affected part when resting to reduce oedema. Simple analgesia may be required for a few days if the wound is sore. - A medical professional should examine the wound on day 7 and

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We can see these principles at work in a bedridden patient. The skin is subjected to three stresses: 1. pressure 2. shear 3. friction

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- It's crucial to act right away to reduce pressure on the area when early indicators of a decubitus ulcer, such as skin reddening or induration, are noticed.

Compared to when a patient is erect, semi-recumbent patients automatically experience higher levels of pressure, shear, and friction on the tissues. These bodily assaults cause the local arteries supplying the location to stretch and maybe avulse. Friction is often seen clinically when a paralyzed patient or unconscious patient is moved across rough bed linens. By itself, the friction causes only abrasions, but it also produces the critical pressure required to produce ulcerations. Shear occurs when a patient shifts in bed and subcutaneous tissue moves over a bony prominence, resulting in injury to the underlying vasculature. Shear is a significant predisposing factor to ulcer formation and enlarges the area of necrosis.

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Decubitus ulcers develop when there is "enough pressure to cause an obstruction inside the skin's microcirculation, which results in the death of the tissue." If the compression pressure is larger than the mean capillary pressure, the process can begin after just three hours of compression in a high-risk location. Prolonged pressure greater than mean capillary pressure causes occlusion of blood vessels, depriving tissues of their vital blood supply. Human skin can tolerate pressure as high as 500 mm Hg for short periods. However, if the perfusion pressure of the venous capillary system (approximately 30 to 40 mm Hg) is exceeded for even two hours, tissue damage will occur. Ischemia is the primary factor in ulceration, and persistent pressure exacerbates the damage.

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Assessment of pressure ulcers

Muscle and subcutaneous tissue are far more susceptible to pressure necrosis than the skin. According to several medical experts, changing the patient at least once every two hours can reduce pressure. However, at night this is often impossible, and in some patients (such as the poorly nourished and the very elderly) even two hours in one spot can result in significant pressure damage. It is important to recognize that 90% of all decubitus ulcers occur in only four places. As expected, 90% of pressure ulcers occur in four places, the sacrum, buttocks, trochanters, etc.

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Common decubitus ulcer locations Location

Incidence

Sacral-ischial

30%

Iliac spine/crest

30%

Femoral trochanters

10%

Calcaneal prominence

20%

Total ulcers

90% 130

The prediction of patients at risk (particularly paraplegics or wheelchairbound patients) has been greatly assisted by the development of riskassessment scores, such as the Pressure Sore Prediction Score (PSPS), utilized in the UK The PSPS is best explained by enumerating the six individual components of the predictive score, as shown below: - Leaning back Propping yourself up in bed for extended periods of time is a categorical "no." - Unconscious Mental confusion may qualify as a “no” answer. - Poor overall This might be an acute/severe sickness, such as paralysis. - Condition Incontinent How often is the patient wet underneath? - Lifts up Can the patient lift himself without help? - A “yes”; answer means that the patient is able to elevate the pelvis. - Gets up and walk A “yes” answer implies a normal, or nearly normal ability to walk

Staging of pressure ulcers I

Non-blanchable erythema of intact skin, the heralding lesion of skin ulcer The area may be painful, firm, soft, warmer or cooler as compared to adjacent tissue

II

Partial thickness skin loss of dermis presenting as a shallow open ulcer with a red-pink wound bed, without slough May also present as an intact or open/ruptured serum-filled blister This stage should not be used to describe skin tears, tape burns, perineal dermatitis, maceration or excoriation

III

Full-thickness skin loss. Subcutaneous fat may be visible but bone, tendon or muscle are not exposed. Slough may be present but does not obscure the depth of tissue loss. May be include undermining and tunnelling NOTE the bridge of the nose, ear, occiput, and malleolus do not have subcutaneous tissue and stage III ulcers can be shallow

IV

Full-thickness tissue loss with exposed bone, tendon, or muscle. Slough or eschar may be present on some parts of the wound bed Often undermining and tunnelling

Unstageable

Full-thickness tissue loss in which the base of the ulcer is covered by slough (yellow, tan, grey, green, or brown) and/or eschar (tan, brown, or black) in the wound bed. A pressure sore that cannot be accurately staged due to the presence of necrotic tissue covering the wound base

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Decubitus ulcer assessment scale Grade of score

Comments

0

Erythema/induration noted (potential sore)

1

2

Blister skin formation Erythema which does not disappear within 30 mins after pressure relieved Superficial skin break in the dermal layers

3

Tissue necrosis involving loss of subcutaneous tissue

4

Tissue cavity formed; cavity extends to bones

The PSPS pressure sore prediction score Sitting up?

Unconscious?

Poor general condition?

Incontinent?

Lifts up?

Gets up and walks?

Yes = 3 yes, but = 2 No, but = 1 No = 0 A danger zone is usually indicated by a score of 6 or more

Prevention of pressure ulcers 1. Skin Care Management -

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Use warm water rather than hot water. Hot water can make the skin more metabolically active and produce dryness, burns, and burns. Use a pH balanced (5.5) cleanser. Astringent soaps can strip the skin of its natural protective oils and antimicrobial acid mantel. Be kind. Avoid vigorously rubbing your skin. Rubbing can cause fragile skin to break due to friction. Pat damp skin to make it dry. Cleanse the skin ONLY as needed. Moisturize regularly.

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2. Injury Prevention -

Avoid massaging any reddish or bony prominences. To prevent sliding, keep the head of the bed below 30 degrees, slightly raise the knee catch, or use footboards. Avoid pushing or dragging a client

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when relocating them; lift them instead. Position client to promote good blood flow. Ensure that the client's feet are not exposed to unrelieved pressure from the footboard. Limit opportunities for friction injuries. Use protective devices between the skin and the source of friction such as socks or cotton bandages. Do not use "Donut" type devices to remove the pressure. Instead, lift the entire area, do not use IV bags or other similar devices under the heels. Reposition clients with limited mobility frequently. Chair-bound clients should be moved every hour. Avoid positioning a client directly on their trochanters. Place pillows between bony prominences.

3. Equipment -

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A wide range of tools, such as mattresses, overlays, customised beds, and cushions, are available to prevent pressure ulcers. They are made of a variety of materials and work by either reducing pressure or relieving pressure. Pressure reduction occurs when the patient ‘sinks’ into a device, thus spreading the weight load and reducing the pressure over the bony prominences. Pressure relief is achieved by the removal of pressure over a bony prominence in a cyclical manner. The NICE guidelines recommend that patients with grade 1 or 2 pressure ulcers should, as a minimum, be placed on a high-specification foam mattress or cushion Patients with grade 3 or 4 pressure ulcers are likely to need a more sophisticated device such as alternating air mattresses or overlays. Selection of an appropriate device will depend on a range of factors such as overall health status, level of mobility, patient acceptability and lifestyle. The tissue viability nurse may be involved in selecting suitable devices for patients with complex problems. Some trusts may have an equipment store to provide, monitor and maintain equipment and to ensure that there is 24-hour access to pressure redistributing devices

Category

Type of equipment

Low tech devices

Highspecification foam Cut foam Gel-filled Fluid-filled Air-filled

High tech devices

Alternating pressure Low air loss Air fluidized Turning beds

Bed

√ √ √

Mattress

Overlay

√ √ √ √ √

√ √ √ √ √

√ √

√ √

Management -

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In order to achieve new granulation tissue, the treatment goal is to debride the eschar by promoting autolysis, or the natural separation of the eschar from the wound bed. Two types of dressing are very useful in promoting autolysis: hydrogels and hydrocolloids.

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Nutritional Support

If the patient is in bed, either of these types of dressing could be selected. If the patient is mobile, then a hydrocolloid dressing may be more practical as hydrogels may squeeze out from behind the secondary dressing during weight-bearing

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Consult a dietitian to develop a meal plan to increase protein and calories Provide nutritional supplements. Maintain good hydration with 6 - 8 glasses of water per day, unless

Wound Care

Pressure Reduction/Relief

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Follow the principles of wound healing, and select wound care products. As with any other wound, pressure ulcers need to be assessed and appropriate treatment goals set. Deep pressure ulcers are often associated with necrotic tissue that must be debrided before the wound can heal. As the necrotic tissue liquefies, the wound may produce a foul-smelling heavy exudate. This should not be mistaken for an infection, although obviously if there are clinical signs of infection they should not be ignored. Patients need to understand what is happening as they may find this phase distressing. NICE recommends that progress towards healing should be reviewed weekly and that the pressure ulcer grade, size, and appearance should be recorded.

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Evaluation -

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Positive outcomes may include: - Wound is healed. - Wound is reduced in size (usually by 1 cm per week). - Reduced pain. - Improved quality of life. - Wound is not deteriorating. - Prevention of Pressure Ulcers

2. Ischemic Ulcers - They are a direct result of a degeneration of the cardiovascular system. - Such degeneration leads to reduced blood flow. - The extremities and subsequent tissue necrosis resulting in the formation of dermal lesions. - There are two subcategories of ischemic ulcers called arterial ulcers and venous ulcers.

Skin Care -

Consider implementing pressure reduction/relief mattresses for all patients at risk or who have developed a pressure ulcer. Obtain pressure reduction/relief seating for patients who are chair bound. Use chairs with tilt/recline features rather than just recline features alone. Implement a repositioning schedule to reduce the length of time spent in one position.

Inspect skin daily and with each episode of incontinence Bathe skin using a mild pH-balanced cleansing product and avoid hot water. Use moisturizers liberally once to twice a day for patients with dry skin

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Ischemic ulcers Arterial

Venous

Cause of ulcer

Arterial occlusion curtails blood flow

Incompetent perforator valves

Initiating factor

Deep vein thrombosis

Location

Arteriosclerosis Atherosclerosis Toes, heels

Pain

Extreme, increase with leg elevation

Medium decreases with leg elevation

Pedal pulses Appearance

Usually absent Punched out lesion with pale or white bed

Usually, present Irregular lesions with brown and blue lesions

Above medial malleolus

capillaries and subsequent leakage of red blood cells into the tissue spaces.

Venous leg ulcers -

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Leg or foot wounds that do not heal after six weeks Venous ulcers of the lower extremities affect 1% of the general population and 3.5% of persons over 65 years of age, with a recurrence rate approaching 70%. The venous system of the legs comprises three parts: - The deep venous system (includes the femoral, popliteal, and tibial veins) - The superficial system, composed of the greater and lesser saphenous veins - The perforator veins that join the deep and superficial systems. Veins have one-way valves that allow blood to flow in one direction, i.e., towards the heart. Failure of these ‘one-way’ valves in the deep and perforating veins allows the backflow of blood from the deep veins to the superficial veins which become stretched and dilated, leading to damage to other valves that were previously competent. This causes abnormally high pressure in the superficial veins, known as venous hypertension, and leads to a rise in pressure in the

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Venous stasis is another category of ischemic ulcer, caused by unrelieved high pressure in the venous vasculature of the lower extremities and thought to be related to incompetent perforator valves. According to the latest theory, when venous valves do not function properly, the venous capillaries overstretch and become more permeable. Large plasma molecules (i.e., fibrinogen) normally retained in blood escape into the extravascular space. Leaking fibrinogen coagulates around the capillary, forming a “fibrin cuff” These cuffs, in turn, are believed to block oxygen transfer to the skin, and also prevent capillary dilation in response to increased demand for blood supply. These modifications cause tissue death and the development of ulcers. In addition to having an uneven shape, edematous tissue and dark hemosiderin colouring surround venous stasis ulcers.

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Assessment DEFINING CHARACTERISTICS Location Anterior, pretibial and gaiter (sock) area, Medial malleolus Skin colour Brown staining or discolouration due to deposits ofhemosiderin Skin Warm, dry, pruritic Pulses Present usually good popliteal and pedal pulses Pain Aching, heavy feeling in legs Ulcer Base Moist and shallow, deep red in colour or yellow with fibrousslough Ulcer Margin Irregular configuration Peri-wound Maybe macerated if exudate copious; may also be dry andflaky Oedema Increases with extremities dependent decreases when limbs are elevated to heart level or above. Mild ankle swelling Discharge Moderate to large amount of exudate

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Intervention Plan: -

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The gold standard for the management of venous ulcers lies in the application of compression therapy. Compression therapy is the application of external pressure to the lower extremity to facilitate Venous blood return. Compression therapy showed: - Reduce distension in the superficial veins, counteracting the high pressure. - Encourage and enhance blood flow in the deep veins. - Restore damaged valve function in some patients - Facilitate the action of the calf muscle pump; restricting the muscle which directs pressure inwards onto blood vessels, thereby increasing venous return. - Force fluid into both the venous and the lymphatic system, thus reducing oedema.

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Reduce the symptoms of venous disease such as aching limbs and pain from the ulcer. - Increase the healing rate of venous ulceration. - Improve skin condition; some studies report increased removal of fibrin during compression therapy. - Enhance fibrinolytic activity needed to increase the healing rate of venous ulceration. - Promote the growth of healthy tissue and prevent concomitant infection. Compression is created by the use of elastic or rigid external layers of bandages. The amount/type applied is dependent upon the extent of peripheral oedema, Measured by ankle circumference, and the expected amount of normal calf muscle flexion. LaPlace’s Law* for compression bandages explains the effect.

LaPlace Law - High compression is contraindicated for patients with the arterial disease Number of layers X Tension SubBandage pressure = Ankle circumference X Bandage width

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(ABI less than 0.8). However, lower compression can be used in patients with an ABI of 0.6 to 0.8. The Ankle-Brachial Index is a noninvasive test used to detect evidence of significant arterial insufficiency.

Arterial leg ulcers ABI Reading Greater than1.0

Results indicate Normal arterial circulation

Less than 0.9

Mild-degree arterial diseases

0.5-0.8

Mixed arterial and venous diseases

Less than 0.5

Arterial disease

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Intervention focuses on appropriate wound compression, if compression therapy is applied inappropriately or to patients with arterial occlusion, it could result in the need for amputation of the limb.

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Evaluation -

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Positive outcomes may include: 1. Wound is healed. 2. Wound is reduced in size (usually by 1 cm per week). 3. reduced pain. 4. improved quality of life. 5. Wound is not deteriorating. 6. Wound does not reoccur.

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Prevention -

Maintenance of compression therapy for life. Maintenance of healthy skin integrity. Prevention of injury to the lower limbs.

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Local wound care -

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The best primary dressing should be chosen after evaluating the wound and the skin around it. The peri-wound skin should be protected from the wound. Skin can be kept moisturized with a simple emollient such as 50% white soft paraffin in 50% liquid paraffin (50/50). If a patient has cellulitis, then the compression bandage should be discontinued and only used once the infection has settled

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Arterial ulcers are caused by arterial insufficiency and occur when circulation to the lower limbs is compromised, usually by atherosclerosis. Such ulcers are common in patients with diabetes mellitus who may suffer from arteriosclerosis and peripheral neuropathy. Arterial ulcers are usually painful, and exquisitely sensitive to touch (except where neuropathy has dulled sensation). They often occur in the lower leg, especially in the toes and heels. Arterial ulcers are not as common as venous ulcers, and they are often more complex to manage because of coexisting diseases and complications. Peripheral Vascular Disease (PVD) is a term commonly associated with arterial insufficiency. However, PVD includes the arteries, veins and lymph vessels and results in chronic, systemic health problems. There is no cure for PVD. The pathogenesis of PAD is arteriosclerosis, a thickening and decreased elasticity of the arterial walls. Atherosclerosis, a form of arteriosclerosis, develops as a result of the accumulation of plaque, lipids, fibrin, platelets, and other cellular debris into and along the wall of the artery. When resting, a person can tolerate up to 70% occlusion of the artery. However, with exercise, the increased demands for blood flow cannot be met and muscle ischemia occurs, causing crampy leg pain; 90% or greater occlusion will reduce flow resulting in pain even at rest.

Risk Factors for PAD: 1. Smoking - Carboxy haemoglobin, which can damage the lining of blood vessels - Altered platelet function with resultant thrombus formation - Decrease in prostacyclin, a prostaglandin that prevents platelet aggregation and promotes vasodilation. In a smoker, 5 - 15% of the oxygen in the blood is replaced with carbon monoxide. 2. Diabetes Mellitus - Peripheral vasoconstriction effects of nicotine reduce the absorption of insulin from s/c tissue. 3. Hyperlipidemia - (Hypercholesterolemia and hypertriglyceridemia) significantly affect atherogenesis. - A serum cholesterol level greater than 220 mg per 100 ml is considered a sign of hyperlipidemia. - Elevated triglyceride levels should be evaluated and may also be indicative of hyperlipidemia.

- Loss of hair 4. Gangrene

Wound assessment DEFINING CHARACTERISTICS Location Anywhere on the legs or feet, especially pressure points, distal to impaired arterial supply Skin Color Blanching with limb elevation to 30 degrees, Rubor with limb dependence Skin Thin, shiny and hairless Nails Hypertrophied, yellow and fragile, clubbing of nails, loss of hair on feet Pulses Absent or faint Pain Severe pain intensified with activity or limb elevation Ulcer Base Pale, grey or yellow with no evidence of new tissue growth Ulcer Margin Well-defined, “Punched-out” appearance. These can be deep wounds Peri-wound Dry, no surrounding inflammatory response. Shiny red Oedema Minimal Discharge Minimal serous or purulent Capillary Refill Greater than 4-5 seconds

Interventions -

Signs and Symptoms of Peripheral Arterial Disease: 1. Pain - pain may be with exercise (intermittent claudication) or nocturnal or it may simply be a pain at rest. 2. Impaired Circulation, manifested by: - Decreased pulses - Skin-temperature changes - Delayed capillary and venous filling - Pallor on elevation - Dependent rubor 3. Ischemic Skin Changes: - Color - Atrophy of subcutaneous tissue - Shiny, taut epidermis

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Invasive procedures - are used in an attempt to restore blood flow in the extremity. This may include vascular surgery. Goals of a comprehensive management plan for arterial ulcers are to: - Reduce or eliminate the cause - Optimize the microenvironment - Support the host - Provide education Eschar debridement may not be recommended. Debridement of the wound won't do anything but raise the danger of infection in cases of severe vascular disease. The wound will not receive the needed WBCs and nutrients to heal. The exposed tissue would then be vulnerable to microorganisms.

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adequate blood supply has been achieved following surgical intervention.

Occlusive moisture-retentive dressings are not recommended in these circumstances. Dry gauze is a suitable choice to keep the wound dry and stop further wound degeneration.

Diabetic foot ulcers -

Evaluation -

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Evaluation indicators should evaluate the goal of treatment. If the goal is to heal the wound, a positive outcome may include: - Wound is healed - Wound is reduced in wound size (usually by 1 cm per week) - Reduced pain - Improved quality of life - Wound is not deteriorating If the goal is to palliate/maintain the wound status, a positive outcome may include: - Reduced pain - Improved quality of life - Wound does not deteriorate - Wound does not become infected

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Prevention -

Cessation of smoking Implementation of a walking program to improve collateral blood flow Prevention of injury Maintenance of skin integrity.

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Local wound care -

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Any necrotic tissue and slough should be removed, and the incision should be maintained moist. This may be achieved by autolytic debridement facilitated by dressings that rehydrate the wound, such as hydrogels and hydrocolloids, or by bio-surgery (larvae therapy). Dressings applied to an arterial ulcer will not improve healing until an

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Foot complications are one of the most common reasons for hospital admissions in patients with diabetes. They are caused as a result of peripheral neuropathy or PAD or a combination of both Sensory neuropathy puts the patient at risk for mechanical, chemical, and thermal trauma. Motor neuropathy results in muscular atrophy in the foot, creating two basic problems - Foot deformities develop and the patient’s gait changes. - These gait changes cause repetitive stresses on areas of the foot, usually a metatarsal head, Callus build-up is the first sign of repetitive stress and will progress to ulceration if the weight is not properly redistributed with special shoes (orthotics). Autonomic neuropathy is the third category of peripheral neuropathy, with distal anhidrosis as its principal symptom. - Anhidrosis causes xerosis (dry skin) and puts the client at risk for developing fissures and cracks. A chronically dry or moist interdigital environment on the foot is a perfect breeding ground for selective bacterial or fungal flora. With repeated stressors from ambulation, these bacteria or fungi that enter soft tissues through cracks and fissures move deeper into the soft plantar tissues and may result in

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infection, gangrene, and even eventual amputation. Also, patients with diabetes experience PAD which results in tissue ischemia. The results: blistering, ulceration, infection and/or gangrene, and, not infrequently, amputation. The main goal is to prevent the occurrence of a diabetic foot ulcer. Patients with diabetes should be encouraged to inspect their feet daily for any changes to their normal skin tissue such as reddening, blisters and areas of dry hardened skin. If the patient is ill in the hospital, then the nurse responsible for their holistic care should undertake this.

Wagner’s classification of diabetic foot ulcers Grade 0 1

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Description of ulcer Intact skin in patients who are at risk Superficial ulcers with exposed subcutaneous tissue Exposed tendon and deep structures Ulcers extend up to the deep tissue and have either associated soft tissue abscess or osteomyelitis Ulcers include feet with partial gangrene Feet ulcers with more extensive gangrenous tissue

Assessment

Diabetic Foot Assessment Ischemia

Ischemia results from atherosclerosis of the arteries of the leg. Assess pedal pulses, skin colour (dusky red or cyanotic blue) and capillary refill

Deformity

Callus Swelling Skin Breakdown Infection

Deformity often leads to the development of vulnerable bony prominences, which are associated with high mechanical pressures on overlying skin. This usually results in ulceration in the absence of protective pain sensation and particularly in those who wear unsuitable shoes. Foot deformities Clawed foot Fixed flexion deformities at the interphalangeal joints. Pes Cavus Abnormally high medial longitudinal arch, leading to abnormal distribution of pressure and excessive callus formation under the metatarsal heads. Hallux Rigidus Limited joint mobility of the first metatarsophalangeal joint with loss of dorsiflexion leading to excessive pressure causing callus formation. Hammer Toe Flexion deformity of the proximal interphalangeal joint of a lesser toe with hyperextension of the associated metatarsophalangeal and distal interphalangeal joints leading to ulceration. Charcot Foot Bone and joint damage in the metatarsal-tarsal region results in rocker bottom foot and medial convexity. Thickened area of epidermis which develops at sites of high pressure and friction. Predisposes to ulceration; impedes healing of ulcer. Any break in the skin over the entire surface of the foot, ankle, between the toes and back of the heel Signs could include ulceration, cellulitis, purulent discharge, and pain in an insensate fool.

Necrosis

Black/brown devitalized tissue.

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Location

Diabetic foot ulcer assessment Most often on the feet, especially weight-bearing surfaces or pressure points. Maybe located between the toes.

Surrounding skin

Dry, thin, crack or fissure. Thick callous pressure points

Ulcer Base

Maybe dry or covered with eschar. Often has deep necrotic areas that go undetected until opened surgically.

Border

Undefined; ulcer may be small at surface and have large subcutaneous abscess. Absent, burning or numbness (Mild to Severe ). Varies; an infected ulcer may have purulent exudate; others may have little serosanguinous discharge.

Pain Drainage Pulses

Usually present (dependent on involvement of arterial component).

Skin Color

Normal; pallor if arterial disease is involved.

3. Patient reports reduced pain.

Prevention -

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4. Patient reports improved quality of life. 5. Wound is not deteriorating. 6. Function is restored. 7. Maintenance of wound condition. 8. Maintenance of skin integrity.

Avoid smoking. Wash and inspect feet daily. Avoid exposing feet to temperature extremes. do not walk barefoot. Do not soak feet. Wear proper-fitting socks and change them daily. Wear proper-fitting shoes and inspect shoes daily for any areas of wear or roughness inside the shoes. Cut nails straight across or, if unable to cut their nails, have a health professional, who is foot care specialist trained, cut their nails Manage their diabetes closely and work with health professionals to try to achieve and maintain good glycemic control. See a health professional immediately if a cut, blister, or sore develops. Do not cut corns and calluses. See a health professional.

Malignant wounds

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Evaluation 1. Wound is healed. 2. Wound is reduced in wound size (usually by 1 cm per week).

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Aetiology 1. Fungating wounds Ulcerated “malignant skin lesions” which are open and drain. They can result from primary cancer, metastasis to the skin from a different tumour site, or a tumour at a distant location on the body. The lesions may look like a rapidly growing fungus or they can present as a cauliflower-like appearance that may ulcerate and form craters. Fungating wounds may result from almost any type of cancer but are most commonly associated with breast cancer. The wounds often become infected with anaerobic and aerobic organisms. 2. Radiation-induced wounds Skin reactions and complications occurring from radiation therapy.

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A reaction may develop that progresses through erythema to dry desquamation and then moist desquamation when the skin receives significant doses of radiation therapy.

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3. Extravasation wounds Results from the leakage of vesicant intravenous fluids or medications into the interstitial tissue surrounding an intravenous site The injury to the tissue is dependent on the specific drug administered, its concentration, the amount of drug extravasated, the length of time the extravasation was occurring and the site of the extravasation.

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4. Malignant cutaneous wounds characterized by visible changes in the skin where an extension of cancer cells is observed through the epidermal/dermal layer These lesions may result from primary cancer or they may develop as a secondary infiltration in the late phases of the disease.

Intervention -

The considerations for dressing selection should also include the following: - Cost - Reimbursement - Local availability - Number of applications required - Complexity of the procedure - Additional patient care needs - Anticipated care provider - Education requirement of care providers - Client comfort

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There are three key objectives when managing a fungating wound. They are: - Wound pain management - Odor management - Control of exudate Radiation wounds - Some require leaving the area open to air - Others suggest covering the area with a cream or non-adherent dressing.

Assessment -

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- Size and shape of the site - Pain - Bleeding Irradiated skin looks dry because sweat glands and sebaceous glands are destroyed. There may also be loss of elasticity, ulceration, necrosis, shedding or nail deformity and malignant tumours. Fibrosis of the lymph glands may cause lymphedema. Extravasation wounds - Manifests as a burning pain and occasionally erythema at the injection site. - Often, there may be swelling or bleb formation

Fungating wounds and malignant cutaneous lesions It is centred on prioritising symptom control and patient comfort over wound healing as the main goals. It is often best to begin the assessment by asking the patient what aspect of the wound is most disturbing for them. The assessment parameters for fungating wounds include: - Appearance - Odor - Drainage/exudate - Presence of infection - Peri-wound Skin

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Extravasation wounds look for the extent of tissue damage as it may not become evident for several weeks and require excision and skin grafting.

Pain Management: - Fungating wounds and cutaneous lesions - Patients' main sources of discomfort are typically severe and traumatic clothing changes. - It's crucial to think about utilizing items that don't stick, may work as a hemostatic dressing to control bleeding, and provide protection to the skin around the wound when choosing dressings for a fungating wound. - Appropriate medication for pain is crucial. - Radiation wounds - May be extremely painful, depending on the depth of tissue involvement and the outward signs of damage. - Cool compresses may help and systemic analgesics should be administered as appropriate. - Extravasation wounds - Can be painful. Depending on which agent has been infused - Cold compresses may be contraindicated so the clinician should know all potential reactions and antidotes before beginning infusion.

Debridement -

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Fungating wound - If necrotic tissue is present, the use of products to encourage autolytic debridement is advised. - It is not recommended to mechanically debride because these wounds often bleed easily and are quite painful. Radiation wounds - Unless areas of necrosis occur, there may be no need for debridement in many radiation wounds. Extravasation wounds - Debridement and surgical repair with skin graft is indicated in some types of extravasation wounds - As few as one-third of all vesicant extravasations will develop ulcerations, therefore surgical debridement is not indicated in all extravasation wounds. Exudate Control

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Odor Management -

The topical application of the antimicrobial metronidazole has been reported to be effective in the reduction of odour by managing anaerobe growth and infection. Odour is not usually a problem in radiation or extravasation wounds unless the tissue becomes necrotic.

It is important to try to determine if the odour is caused by necrotic tissue, infection, or by saturated dressings. Odor can be controlled by wound cleansing, use of wound deodorizers, debridement, and treatment of infection

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The use of exudate management products that can absorb high volumes of exudate will provide appropriate exudate management in the wound and facilitate a dressing change schedule that will not be too traumatic to the patient. Radiation and extravasation wounds do not usually have exudate management problems.

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The clinician should observe the dressing to look for strike-through and base the decision to change the dressing on the level of exudate present in the dressing and the patient’s report of comfort with the dressing.

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Evaluation -

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The key indicator when evaluating success is to ask the patient if the care being provided has met their needs and determine if it has improved their quality of life.

Quality of Life -

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Lifestyle factors: social, cultural and economic Aesthetics Management of bleeding Odor and exudate control Comfort: psychological and spiritual Pain management Control of treatment-induced side effects

In summary, wound assessment requires an accurate clinical history, which includes the duration of the wound, any previous wounds, history of trauma, wound characteristics, underlying medical conditions, smoking, medications, and allergies. Wounds can be classified into four categories based on their appearance: necrotic, sloughy, granulating, and epithelizing. The wound site, surrounding skin, and exudate level are additional crucial considerations when choosing a dressing. If a wound is oozing, a dressing must absorb and control the exudate levels, with the dressing having a different absorption capacity.

Irradiated wound -

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Irreversible and chronic effects include atrophy, scaling, telangiectasia, subcutaneous fibrosis, and necrosis. Early radiation injury is due to the depletion of rapidly dividing cells (proliferating tissue such as mucosa). Slowly proliferating or nonproliferating tissues experience late damage (months to years later). Long-term complications (months to years later) are caused by the injury of late-responding tissues (skin, subcutaneous tissue, muscle, bone. glands, CNS) where progressive fibrosis occurs. Because the cellular milieu of irradiation wounds is still unknown, they are treated similarly to chronic wounds.

Hemostasis, inflammation, angiogenesis, collagen synthesis, turnover, epithelialization, and contraction are necessary for healing. A delay in the earlier phases of healing interferes with all subsequent stages of the healing process. Radiation impairs healing by microvasculature obliteration, fibrosis, and disruption of cell proliferation. Irradiation effect on the skin depends on the following variables: the area and volume of tissue, fractionation, total dose, type of radiation, and skin type. Reversible effects include dry desquamation, hyperpigmentation, and hair loss.

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Pictures Chapter 3

Figure Non healing traumatic wound. This patient had a surgical procedure to repair her Achilles tendon. Postoperatively, she was placed in a cast to immobilize her leg. This type of laceration just above the heel was present after the cast was removed and has not healed for several months. There is considerable induration and probable fibrosis around this wound. As in other situations like this, the fibrotic/ sclerotic component may be interfering with the healing process. Topical retinoic acid (shortcontact method) was used to stimulate granulation tissue, but did not improve this particular wound. She was lost to follow-up, but our plan was to surgically remove the fibrotic tissue around the wound and then perform an autologous graft.

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Infection Dermatitis from ant bite

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Figure A diabetic ulcer and Charcot foot. This patient had long-standing diabetes mellitus and neuropathy. He presented to us with an ulcer on the sole of his foot. The mid foot is collapsed, giving a flat appearance to the sole. In these circumstances, progressive damage to the tendons and collapse of the bones leads to excessive pressure and persistent ulceration. Charcot foot is seen in several diseases characterized by neuropathy, such as diabetes, syphilis, and leprosy. The etiology of the Charcot foot remains unknown but is thought to be initiated by an inflammatory process. In this particular case, the patient has some redness on the plantar surface, suggesting that one needs to investigate whether this represents a chronic Charcot foot or whether an inflammatory process is still present

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Figure A diabetic wound treated with a living dermal skin substitute. This neuropathic heel wound in a diabetic patient shows excellent granulation tissue. Because of the beefy red wound bed, we were concerned about colonization with S. aureus, but bacterial cultures proved negative. The wound should heal with appropriate off-loading measures. Bioengineered skin products can be used to accelerate the healing process.

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Figure pressure ulcer on the knee in a paraplegic patient. Such ulcers on the medial aspects of knees are not uncommon in patients with spinal cord injury and spastic paralysis. In this case, there was almost constant trauma to the medial aspect of both knees. Although much of the ulcer has excellent granulation tissue, the center is necrotic and in need of debridement. Management of these ulcers involves the use of protective dressings, such as hydrocolloids, or foam padding.

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Figure Choosing a wound dressing/limitations in highly exudative wounds. The photograph shows the challenges and consequences of keeping a compression bandage over highly exudative leg wounds. In this case, the bandage has been cut and removed, showing the massive exudate that accumulated underneath. The drainage is often foul smelling, which can be very upsetting to patients and can fool inexperienced clinicians into thinking that the wound is infected. Ways to deal with this problem is to use an absorbent wound dressing, such as foams, hydrocolloids, alginates, and to change the bandages more frequently. Other clinicians have used antimicrobial agents or adsorbent material within the bandages to decrease the bacterial burden and the foul odor.

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Figure Choosing a wound dressing/exudate and purulence. Highly exudative and/or purulent wounds require a localized approach, because systemic antibiotics are often not effective or indicated. The ankle ulcer shown in Panel A is highly exudative and contains a high bacterial burden (colonization). In this case, we will prefer the use of foam, calcium alginate, or a hydrofiber dressing with or without silver. Another possibility would be cadexomer iodine. The extensive ulcerations shown in Panel B are not as exudative but probably also contain a very high bacterial burden. Colonization here is more likely than cellulitis, because there is no severe pain or fever and there is not much redness around these ulcers. Extensive surgical debridement in the operating room is an option, perhaps with hydrosurgery. Antimicrobial dressings, containing either silver or iodine, will be helpful.

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Figure Wound measurement systems There are several ways and devices to measure the wound area and perimeter. Some of these methods use digital photography. Other methods, as in this case, rely on planimetry by tracing the wound and computing the tracing on a digital pad. Shown here (Panels A – C) is an example of a disposable tracing grid system that can be used to measure the wound area. As shown in Panel A, this particular product consists of 3 layers: the 2 superficial layers are translucent and the 3rd is a white backing layer. After this backing layer is removed, the 2nd (contact) layer is placed against the wound. Panel B shows the contact layer over the pad, ready for measurement by using a specialized retracing pen. The area of the ulcer can now be traced over the top layer, which is ultimately separated from the underlying second contact layer that will be discarded. Panel C shows an example of a tracing of a venous ulcer.

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Figure Healed ulcer and chronic lipodermatosclerosis. There are several presentations of chronic lipodermatosclerosis (LDS). The hypo pigmented area on the medial aspect of the lower leg is an ulcer that has healed recently. Interestingly, it takes several months or even years for the pigment to return to the previously ulcerated site. The surrounding hyperpigmentation and the hardness of the skin are classic for chronic LDS. There is usually little pain at this point, although some discomfort can be felt upon prolonged walking. This 64-year-old man needs to wear graded compression stockings for the rest of his life, so as to avoid recurrence of the ulcer.

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Figure Management of dermatitis (irritant or allergic). The surrounding skin of chronic wounds, especially those caused by venous disease, is frequently complicated by scaling, redness, warmth, and other signs that, collectively, we call dermatitis. Not infrequently, it may become difficult to distinguish dermatitis from cellulitis. In our experience, topical antibiotics and emollients are the most common reasons for dermatitis. In treating this complication, we try to avoid other topical agents and advise discontinuing all topical medications. In some cases, we prefer to use films, hydrocolloids, or hydrogels to treat the dermatitis. Dermatitis can present in many ways. Panel A shows a dermatitis over a leg stump (below the knee), which prevented the patient from using his prosthesis. We excluded a dermatophyte infection and also biopsied the scaly area to rule out a squamous cell carcinoma. A hydrogel will be helpful in the management. Panel B shows a severe dermatitis on the dorsum of the foot and between the toes. The patient had onychomycosis, but the dermatitis was not due to a dermatophyte infection. Reluctantly, we did have to use a topical corticosteroid ointment. The use of ointments, which contain less chemicals and possibly sensitizing ingredients, is preferable to the use of creams. Panel C shows yet another example where we would use a hydrogel to control the severe leg dermatitis occurring in the setting of venous insufficiency. In severe and unresponsive cases of dermatitis, after ensuring that no infection is present, we may choose to use systemic corticosteroids for a short period of time.

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Figure Chronic lipodermatosclerosis and dermatitis. In colder climates, the clinical picture of venous disease can be somewhat different, in that the involved skin is dry and scaly. This 82-year-old man had a very distinctive scaly plaque on his shin, which was not painful or tender. These plaques were present bilaterally, and we also thought of the possibility of pretibial myxedema. However, a biopsy showed no evidence of increased hyaluronic acid (as in pretibial myxedema) and there were typical histological findings of venous disease (i.e., increased tortuous vessels, hemosiderin deposition).

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Figure Removing undermined tissue from a pressure (decubitus) ulcer. This patient had a pressure (decubitus) ulcer that may appear superficial upon early inspection. However, careful examination of the wound edges and the use of a sterile cotton applicator show that the ulcer was undermined by about 2 cm, almost circumferentially (Panels A – C). It is important that undermining of pressure ulcers be assessed carefully and that proper debridement be done to remove the undermining. Some clinicians may disagree with the need to remove the undermining, but we feel that bacteria thrive under that skin overhang. The undermining also suggests that unwanted pressure to the wound is continuing to occur.

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Figure A sinus tract in a pressure (decubitus) ulcer. In this patient the undermined area has been mapped out and removed (Panels A – B). However, there is a sinus tract in the middle of the ulcer (Panel B). The sinus tract was then excised (Panel C). In addition to adequate debridement, the reduction of pressure against the ulcer with the use of specialized surfaces and proper positioning of the patient are essential to healing. Medical management of a patient with a pressure ulcer includes careful attention to wound bed preparation. This even includes proper attention to optimization of the patient’s nutritional status and appropriate surgery for urinary or fecal diversion. Frequent assessment for possible infection should always be done. One unresolved question is whether certain dressings, particularly those that are rigid or quite adhesive, add to the effect of pressure. It’s sadly ironic that dressings could contribute to the amount of pressure against the wound. In our experience and experimentation, it might be that gel dressings are less likely to do so, but more work is required to make a final determination.

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Figure an ischial pressure (decubitus) ulcer. Wound bed preparation is critical in these cases of very difficult-to-treat pressure (decubitus) ulcers. Treatment requires a combination of approaches, including surgical debridement, negative pressure, and appropriate dressings that do not augment the level of pressure by forming a rigid unit with the ulcer. In this particular case (Panel A, at baseline) there was improvement with these approaches and with the use of a hydrogel dressing (Panel B), which tends to be more flexible than other dressings. However, the granulation tissue seen in Panel B is still not optimal, and the plan is to use additional treatment with negative pressure and bioengineered skin. More surgical debridement will be required, as there is undermining and the possibility of sinus tracts.

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Figure Arterial ulcers. This 79-year-old woman presented with multiple non healing ulcers. It was unclear whether the etiology was related to her history of CREST (calcinosis, Raynaud’s phenomenon, esophageal problems, sclerodactyly, and telangiectasia) syndrome. CREST can be thought of as an exaggerated form of the limited variant of systemic sclerosis (scleroderma), and it’s also associated with anticentromere antibodies. The deep, punched out appearance of the ulcers, together with the visible tendon sheath and pain on exposure to air pointed to an arterial component (Panel A). Vascular studies confi rmed that the ulcers were due to arterial occlusion. In order to restart/reset the healing process, extensive debridement with hydrosurgery was performed. Thereafter, topical negative pressure was applied to stimulate the granulation tissue, and a stent was placed in the left leg. Five weeks later there was definite improvement in the wound bed and tendon (Panel B). A plan was made to continue the topical negative pressure until there was substantially more granulation tissue that would allow us to graft the ulcers.

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Figure A pressure (decubitus) ulcer over a hip prosthesis. This had been a recurrent ulcer. The white area was immediately over the prosthesis (Panel A). Extensive debridement with a scalpel and scissors showed the ulcer to be much larger and deeper than initially assessed (Panel B). Probing of the edges is always a useful maneuver to judge the extent of deep tissue injury. This is often done repeatedly during debridement, to be sure of removing all necrotic and undermined tissues (Panel C). Further debridement over the middle of the ulcer showed that the hip prosthesis was directly exposed (Panel D). The patient had to be taken to the operating room to have the hip prosthesis removed. We felt that there was no choice at that point.

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Figure Debridement of an arterial ulcer and stimulation with pinch grafting. This 70-year-old woman had inoperable arterial insufficiency, diabetes, and this non healing ulcer of the big toe (Panel A). She also had severe neuropathy and an insensate foot. The ulcer developed after she stepped on a sewing needle that was stuck in her carpet. She repeatedly refused amputation, even when imaging studies suggested the possibility of osteomyelitis. Systemic antibiotics were given intravenously for 6 weeks, with some improvement. Here one sees substantial necrosis of the ulcer bed. There is also a yellow area of exudate and fibrinous material in the center of the wound bed. No sinus tract was present and the underlying bone was not visible. After the application of a lidocaine/prilocaine anesthetic combination followed by infiltration with local lidocaine infiltration, a scalpel was used to remove the necrotic areas (Panel B). Right after the debridement in the outpatient setting, a few pinch grafts of skin from her abdomen were applied to the ulcer bed with the goal of activating the wound bed and stimulating healing (Panel C). The photograph in Panel C was taken a week after pinch grafting. The applied skin has not taken and has mostly fallen off. However, the “pharmacologic” action of the autologous grafts may have stimulated ulcer healing (Panel D). This approach is simple, cost-effective, and worth trying in difficult situations like this one.

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Figure Wegener’s granulomatosis/importance of local wound care. She has an established diagnosis of Wegener’s granulomatosis. Patients with this condition develop sinusitis, pulmonary disease, and renal involvement; these findings do not occur in a uniform sequence. The condition is commonly associated with serum autoantibodies to cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). The photograph shows a large necrotic ulcer that needed surgical debridement to accelerate healing (Panel A), and Panel B indicates the appearance of the ulcer about 3 weeks after the initial debridement. There is now good granulation tissue and some evidence of re-epithelialization. Six weeks after the initial presentation, there has been rapid healing (Panel C). She was kept on her systemic immunosuppressive therapy for Wegener’s granulomatosis, which generally includes prednisone and cyclophosphamide; sulfa drugs are used occasionally. This case illustrates the importance of following basic wound care principles in conditions that are inflammatory. We find that some clinicians often emphasize systemic therapy in these cases without proper attention to basic wound care. .

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Figure Examples of digital ulcers in systemic sclerosis (scleroderma). Digital ulcers are a cause of great morbidity in these patients. Panels A – D show some challenging clinical situations. It is our view that digital ulcers in these patients should be evaluated by MRI before embarking on any intervention; osteomyelitis and septic arthritis can be difficult to detect clinically. It should be noted that ulcers on the fingertips are likely due to poor vascular supply, and that the digital blood vessels are obstructed and do not respond well to vasodilators. Still, some systemic vasodilator therapy is worthwhile, particularly with calcium channel blockers and sildenafil l. Care must be taken not to lower the blood pressure to the point that vascular flow is adversely affected. Bone seems to be exposed in Panel A. Systemic antibiotics may be needed for several weeks, but the possibility of amputation is high. The finger in Panel B needs to be surgically debrided to evaluate the presence of bone involvement. If the bone is not involved, enzymatic debridement could be initiated. A similar situation is present in Panel C. Of course, in all of these three cases one would be wise to obtain an MRI at baseline. Panel D shows the typical indentation (pitting scars) present on the pulp of the finger in many patients with systemic sclerosis. It is probably due to ischemia and collapse of the underlying tissues.

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Figure Debridement/hydrosurgical approach. In the last few years, methods for achieving thorough debridement of wounds with high-powered water devices have improved and progressed substantially. This type of debridement is known as hydrocision/hydrosurgery. It generally still requires general anesthesia and an operating room setting for large wounds. Compared to scalpel/surgical debridement, it has the advantage of accomplishing a very extensive and rapid removal of necrotic tissue even in deep wounds. It shares with surgical debridement the disadvantage of often not distinguishing between viable and nonviable tissue. Panels A through D show the use of hydrocision in complex wounds precipitated by trauma (Panels A and B: foot trauma and fractures; Panel C: development of compartment syndrome on the leg; Panel D: debriding necrotic tissue of a below the knee amputation stump). There are various configurations to the hydrosurgery tip associated with these devices and they all deliver water at very high pressures.

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Figure Surgical debridement without anesthesia. Unfortunately, we sometimes see patients with severe neuropathy involving the upper and lower extremities. The only advantage is that in such cases surgical debridement can be accomplished without anesthesia. Panels A through C in this elderly man with syringomyelia and blistering of the dorsum of the hands show the progression of surgical debridement in one setting. Panel D shows a photograph taken several weeks later and illustrating remarkable healing. The light colored skin indicates recently healed portions of the wound. This is because the pigment largely lags behind during the process of re-epithelialization.

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Figure Debridement/the use of maggots. Maggot debridement therapy (also known as biodebridement or biosurgery) is the intentional introduction of fly larvae (generally commercially available maggots) into a wound for debridement of necrotic tissue. In the United States, maggot therapy can be prescribed for soft tissue wounds and non-healing necrotic skin (i.e., postsurgical wounds, venous ulcers, etc.). It is approved by the FDA. These fly larvae are placed on wounds and left in place under a cage-like dressing for approximately 2 days. Panel A shows a company container with maggots (about 1–2 mm) clinging to the wall and to the bottom. One substantial problem is to ensure that the maggots do not escape and contaminate the clinical setting.

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Figure Debridement/the use of maggots/dressing for bio debridement. Panels A through D illustrate the application of the maggots and the resultant stimulation of granulation tissue free of necrotic material. As mentioned, containment of the larvae and avoiding their escape is critical. Panel A shows the application of multiple dressings that create a “cage” for the larvae. Panel B shows engorged maggots over an improving wound bed. Since maggots can affect keratin, there has been some increased redness around the wound. It is important to realize that maggots don't have teeth and don't chew the tissue. Rather, they deliver enzymes that break down the wound tissue and they are able to then suck the fl uid. Panels C and D show a progressive improvement of the wound bed in this man with rheumatoid ulcers.

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Extremity whirlpool H Tao, JP Butler, T Luttrell - … of the American College of Clinical Wound ..., 2012 – Elsevier

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A: Image of the luminescent bacteria within a wound before irrigation, that is, baseline luminescence. B: Image of the luminescent bacteria remaining in the wound after 9 L of pulsed irrigation Ref: Comparison of Bulb Syringe and Pulsed Lavage Irrigation with Use of a Bioluminescent Musculoskeletal Wound Model Major Steven J. Svoboda, Terry G. Bice, Heather A. Gooden, Daniel E. Brooks, Darryl B. Thomas and Joseph C. Wenke J. Bone Joint Surg. Am. 88:21672174, 2006. doi:10.2106/JBJS.E.00248

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Figure: ULTRASOUND DEBRIDEMENT DEVICE This 25 kHz ultrasound generator (Sonoca 180) has 3 debridement hand pieces with different probe tips. Ref: Wound Debridement with 25 kHz Ultrasound Margaret McCarty Stanisic Froedtert Memorial Lutheran Hospital Barbara Provo Sinai Samaritan Medical Center, Milwaukee David L. Larson Medical College of Wisconsin Luther C. Kloth Marquette University, [email protected]

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Venous ulcer before ultrasound debridement This wound is located on the edematous left medial ankle. Ref: Wound Debridement with 25 kHz Ultrasound Margaret McCarty Stanisic Froedtert Memorial Lutheran Hospital Barbara Provo Sinai Samaritan Medical Center, Milwaukee David L. Larson Medical College of Wisconsin Luther C. Kloth Marquette University, [email protected]

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Venous ulcer after ultrasound debridement Ref: Wound Debridement with 25 kHz Ultrasound Margaret McCarty Stanisic Froedtert Memorial Lutheran Hospital Barbara Provo Sinai Samaritan Medical Center, Milwaukee David L. Larson Medical College of Wisconsin Luther C. Kloth Marquette University, [email protected]

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Venous ulcer before ultrasound debridement This wound is located on the right anterior edematous leg. Ref: Wound Debridement with 25 kHz Ultrasound Margaret McCarty Stanisic Froedtert Memorial Lutheran Hospital Barbara Provo Sinai Samaritan Medical Center, Milwaukee David L. Larson Medical College of Wisconsin Luther C. Kloth Marquette University, [email protected]

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Venous ulcer after ultrasound debridement Ref: Wound Debridement with 25 kHz Ultrasound Margaret McCarty Stanisic Froedtert Memorial Lutheran Hospital Barbara Provo Sinai Samaritan Medical Center, Milwaukee David L. Larson Medical College of Wisconsin Luther C. Kloth Marquette University, [email protected]\

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Swap for culture

Figure Pain scale: documenting pain for both investigational and non-investigational patients. This visual scale may be used to document and semi quantitavily assess pain in patients with chronic wounds. It is surprising how reproducible these visual scales are, but investigators often rely on more than one instrument to ask patients about pain or other symptoms. (Copyrighted, P. Carson, 2011)

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Examples of wound types:

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Classification of wounds (slideshare.net)

Figure Hematoma after breast surgery. This large hematoma developed following surgery for duct ectasia. The clot needs to be removed and all bleeding vessels need to be tied or cauterized. A pressure bandage will be applied. Consideration should also be given to the use of bioengineered constructs or tissue rearrangement.

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Figure Squamous cell carcinoma. This man had received political asylum after escaping from a Central American totalitarian country. While in prison there, he had received a bayonet injury to both legs more than 20 years earlier. The wound never healed and he refused further treatment. Several years later, the wound began to enlarge and showed increasing amounts of exudate and necrosis. Multiple biopsies confirmed the clinical suspicion that this represented a squamous cell carcinoma. It was poorly differentiated, pointing to an unfavorable prognosis. The patient vehemently refused amputation and was treated for a while with surgical debridement, occlusive dressings, and Mohs micrographic surgery to decrease the tumor burden. However, the cancer extended to the bone and osteomyelitis became evident. He eventually agreed to leg amputation. However, a few years later he died from metastatic squamous cell carcinoma, most likely from this leg cancer.

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Figure Ulcerated squamous cell carcinoma and diagnostic difficulty. This ulcerated shin plaque was present for more than 5 years. When he was referred to us, we suspected a malignant process, such as amelanotic melanoma, basal or squamous cell carcinoma, or an appendegeal skin tumor. With the lack of scaling, squamous cell carcinoma would not be at the top of the differential diagnosis. We decided to perform a shave biopsy. While generally superficial, a shave biopsy samples a larger area of the lesion of interest. The histology was nonspecific and showed no evidence of squamous cell carcinoma. However, we were still suspicious and did not accept the negative findings, especially after we analyzed the histological slides ourselves (Figure 6.14b). A larger, excisional biopsy was done and that specimen did show an invasive squamous cell carcinoma. The patient underwent Mohs micrographic surgery, which should be curative. This particular case illustrates the importance of correlating the clinical findings and impression with histological findings. Persistence is needed when a tumor is suspected.

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Figure Basal cell carcinoma of the leg initially thought to be a traumatic wound. This elderly woman has atrophic and fragile skin. She developed an ulcer on her shin (Panel A) which was first attributed to trauma. However, the ulcer failed to heal after several months. Upon our close evaluation of the wound bed we noted areas with a “pearly surface” (Panel B). This appearance and lack of healing suggest a skin cancer, particularly a basal cell carcinoma.

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CHAPTER

4 Omnia Hussein Ibrahim , Omnia Alaa El-Din Abd El-Salam , Ibrahim Ahmed Elsherbini

Introduction To Wound Dressing Materials Polymeric dressing materials became inevitable for skin tissue repair or healing with time With the renewal of cognitive concepts and the innovation of therapies and technologies, including stem cell therapy, 3D printing, and electrospun polymer, the composition and structure of skin repair and wound dressing biomaterials are becoming more and more perfect and reliable.

-

-

The Criteria for ideal dressing material are as follows (Turner’s criteria):

History of wound dressings -

-

-

-

-

1. It should be non-adherent to the wound bed. 2. It should be impermeable to bacteria. 3. It should maintain a moist wound environment. 4. It should be absorbent. 5. It should be non-toxic, and nonallergenic. 6. It should require a minimal change of dressings. 7. It should be cost-effective with a long shelf-life. 8. It should be easy to apply and remove.

In the eighties, the wound dressings were classified according to their wettability degree into dried and wet dressings. The traditional or dried dressings maintained the wound area dry, reduced the wound size from view, allowed to absorb of all wound exudates and fluids causing leakage and provided further contamination Thus, this behaviour was classified as hostile to bacterial proliferation and also to the viability of mammalian cells and tissue repair. According to the last investigations, it was found that in the case of dried dressings, a scab can cover the whole wound area, which decreases the epithelialization rate and inhibit the dressing rate. Therefore, the gauze-cotton dressings (dried dressings) which were earlier frequently utilized as wound dressings became now not so useful because of their own drawbacks.

It was demonstrated that wound healing with wet dressings is faster than that with dried dressings. This fact is ascribed to the healing and the renewed skin without the formation of eschars or inflammation; can be only taken place in a wet environment

Characteristics of wound dressing

Importance in wound healing

Providing a moist wound environment

Prevents dehydration and cell death Promotes epidermal migration and angiogenesis Maintains moisture at the wound bed Exudate is essential for the wound healing process but excess exudate can cause healthy tissue maceration, resulting in a chronic wound Oxygenation controls exudate levels and stimulates epithelization and fibroblasts Microbial infections delay the wound-healing process by prolonging the inflammatory phase and by inhibiting epidermal migration and collagen synthesis Removal of adherent dressing can be painful and can cause further damage to granulation tissue An ideal dressing should assure the woundhealing process at a reasonable cost

Removal of excess exudate Allows gaseous exchange Prevents infection

Low adherence and painless removal Cost-effective

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Traditional wound dressings 1. Gauze products - For many years, gauze swabs have been used in wound care as both a main dressing in direct contact with the wound and as a secondary dressing over a primary dressing. 2. Films - Film dressings are made from a thin layer of polyurethane with an adhesive coating. 3. Foams - Foam dressings are made from polyurethane foam and generally have a waterproof backing 4. Hydrogels - Hydrogels are aqueous gels made from different materials - Hydrogels can absorb and retain the wound exudates 5. Hydrocolloids - Hydrocolloid dressings are generally made from a polyurethane film with an adhesive mass attached to it to form a flexible wafer. 6. Sponges - Sponges are foam-like, solid structures that can absorb large amounts of liquid due to their high porosity.

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Name of the dressing

Advantages

Disadvantages

Indication

1- Gauze-cotton

-

Easily available

-

Sticks to the wound.

Moist wound

dressing

-

Cheap.

-

Painful during change.

-

Good absorbing capacity.

-

Low gas permeability.

-

Can damage epithelium.

-

Not truly occlusive.

-

Requires frequent change.

-

Could leave residues activating the immune system towards granuloma formation

- Keep the wound dried which decreases the epithelialization rate and cell proliferation. - Not suitable for chronic wounds.

2- Transparent films

-

Provide a moist wound

-

environment. -

Ensure gas exchange.

-

Prevent contamination from

Nonabsorbent, hence not

Superficial

useful in exudative wounds.

wounds and surgical sites.

external bacteria. -

Easy to adapt and remove without causing patient pain

3- Foams

-

Remarkable high absorbance

-

capability. - Thermal insulation.

Need exudates to function,

Exudate-rich

hence not suitable for dry

wounds.

wounds

- Gas exchange.

4- Hydrogels

-

Show discrete sorption capability.

Less effective in facing

wounds with low

- Allow gas exchange.

bacteria contamination

to moderate

- Avoid patient pain during their

compared to occlusive

exudate

removal.

-

dressings and thus, they are

- Enhance tissue granulation.

generally used in conjunction

- Able to lower th ewound bed

with anti-microbial agents.

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temperature up to 5 °C.

-

- Maintain a moist wound

Require a secondary dressing such as an absorbent pad

environment, which in turn promotes autolytic debridement. - Structure allows transporting of bioactive molecules e.g., antibiotics to wound centre. - Has significant flexibility and elasticity to adapt wounds located in different body sites.

5- Hydrocolloids

-

Absorb large amounts of fluids

-

and consequently change into

Cannot be used in anaerobic

Highly exudative

infection/dry wounds.

wounds

gelly-like masses -

Keep amoist environment.

-

Unlike hydrogels, the outer layer of hydrocolloids can more efficiently seal the wound bed and, thus, act as an efficient barrier against bacteria and pathogens without the need for secondary dressings.

-

Able to speed the healing process up by intensifying the autolysis.

6- Hydroconductive

-

Show a specific multilayer structure able to absorb exudate,

dressings

and remove debris from the wound bed.

7- Sponges

-

High porosity.

-

Mechanically weak.

-

Thermal insulation.

-

May provoke skin

-

Suitable in moist environments as it absorbs the wound exudate.

-

Enhance tissue regeneration.

maceration. -

Unsuitable for third-degree burns or wounds with dry eschar.

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Moist wound

2. Phenolics - Tannins, cinnamic acids, phenolic acids, and phenylpropanoids have antimicrobial and antioxidant properties. - Tannins bind to proteins and carbs reducing their digestibility thus inhibiting microbial growth. Tannins increase the woundhealing process via, chelating free radicals, improving wound contraction, and increasing capillary vessel, and fibroblast formation. It also has antioxidant properties. - Plants such as Ageratum conyzoides, Punica granatum, Strobilanthes crispus, etc. contain tannins. 3. Saponins - Are glycosides of both triterpenes and steroids. They have antioxidant and antimicrobial activities, saponins thus increase contraction and epithelialization. 4. Alkaloids - Are cyclic compounds containing nitrogen. They have analgesic, antispasmodic, and bactericidal properties. - The extracts of plants such as Adhatoda vasica, Berberis lyceum, Catharanthus roseus, etc. are rich in certain alkaloids, 5. Quinones - are aromatic rings with two‐ketone substitution. - The roots of plants such as Alkanna tinctoria and Arnebia euchroma have antimicrobial and antioxidant properties. - N.B. The paper contains a table mentioning ethnobotanical claims of the herbs having wound‐healing activity.

Herbal dressing: -

-

-

-

-

Therapeutically active agents present in medicinal plants increase wound healing and regeneration of the lost tissue. These phytomedicines are cheap and affordable and are also safe. Herbal extracts can stop bleeding from fresh wounds, limit microbial growth, and speed up wound healing. The increased healing activity is attributed to free-radical scavenging. While increased healing speed is due to bioactive compounds in plants that increase the strength of collagen fibres. Bioactive constituents in medicinal herbs are defined as secondary plant metabolites having pharmacological or toxicological effects. They have therapeutic activities such as hypoglycemic, antidiabetic, antioxidant, antimicrobial, anti‐ inflammatory, and anticarcinogenic. The most common phytochemicals are saponins, tannins, flavonoids, alkaloids, and quinones.

1. Bioflavonoid - include anthocyanins, flavonols, flavones, flavanones, flavan‐3‐ol, and isoflavones. - Flavonoids enhance the healing process and helps wound contraction and epithelialization rate. They also have antioxidant properties. - Plants such as Moringa oleifera, Cuminum cyminum, and Flaveria trinervia, are rich in various flavonoids and thus used for wound healing.

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membranes, and commercial dressings. - The authors observed that electrospun membranes with 31.2 mg/mL of CA extract increased the fibroblast proliferation up to 93% of cell viability. - The slow release of the drug provided better physical support for cellular proliferation. - Asiaticoside‐loaded alginate films did not have adherence toward the skin cells and were nontoxic to skin cells. 3. Azadirachta indica - It has along with its anti‐ulcer effect, antifungal activity, antibacterial, antiviral activity, anticancer, and antioxidant activity. - indica into collagen biocomposite film has a potent anti‐inflammatory activity and nitric-oxide scavenging activity. - A research investigated the potential of electrospinning four different plant extracts A. indica, Indigofera aspalathoides, Memecylon edule (ME), and Myristica andamanica, along with PCL for skin‐tissue engineering. - M. edule‐incorporated PCL possessed better cell density and ample cell‐to‐cell communication - M. edule extract containing nanofibers also acted as a stem‐cell slot 4. Tecomella undulate - Crude bark extract of T. undulates obtained from the stem contains tecomin, and β‐D‐glucoside is used as a remedy for wound healing. - The extract was released rapidly in a few hours followed by slow release over 24 hours in an acetate bufferreleasing medium.

Herbal Constituents-Incorporated Wound Dressing 1. Aleo vera - Used in the past in dermatological conditions - The leaf gel contains water for moister, prostaglandins for inflammation, and glycoproteins for cell proliferation. - Improves collagen content within the wound - Consistency of the material holds up to 5 days which is ideal - Bioactive constituents present in AV help in collagen secretion. - Nanofiber membranes also provide better cell adherence, nutrient supply, and protection against contagious pathogens. - AV gel into chitosan provided adequate roughness, degradation rate, and mechanical properties. - The AV is incorporated into the nanofiber made with natural (gum tragacanth) (GT) and synthetic polymer (PCL) - PCL/GT/AV nanofibers have mechanical strength and hydrophilic nature and also maintain structure after biodegradation test. 2. Centella asiatica - Asiatica (CA) is composed of triterpenoids (such as asiatic acid, madecassic acid, madecassoside, and asiaticoside) - Asiaticoside, a trisaccharide triterpene, is identified as the most active compound associated with wound healing. - The results of an experiment show that the wound areas covered with membranes exhibited more collagen deposition with more capillaries than with gauze, neat gelatin

193

-

6. Chamomilla recutita - Its therapeutic values are because of various phenolics and flavanoids, apigenin, quercetin, patuletin, luteolin, and their glucosides present. - Apigenin is the rarest flavonoid present in chamomile flowers and shows a great effect on wound healing. - The nanofibers with 15% chamomile extract could cure the wound up to 99 ± 60.5% after 14‐ day posttreatment periods. 7. Hypericum perforatum - H. perforatum has a vast range of bioactive effects such as depression, anti‐inflammatory, antimicrobial (E. coli and S. aureus), antioxidant agent, and wound‐healing effects. 8. Ginger - Ginger (Zingiber officinale Roscoe, Zingiberacae) is widely used in food as a spice and herbal medicine with insignificant adverse effects. - [6]‐gingerol is reported to have antitumorigenic, anti-inflammatory, antiapoptotic, antihyperglycemic, antilipidemic, antiemetic, and analgesic activities. 9. Sago Starch - Soya protein and sago starch cross‐ linked with (gluteraldehyde G) as wound‐dressing materials cause reepithelialization and remodelling of the skin had been achieved by providing a wet environment at the wound site and thereby hastening the migration of keratinocytes. 10. Grape Seed - Grape seed extract (GSE) is a mixture of polyphenols composed of procyanidins, catechin, epicatechin, gallic acid, and epicatechingallic acid ester.

PCL/PVP fibre mats showed activity against pathogenic bacteria Pseudomonas aeruginosa, S. aureus, and Escherichia coli. - Experiment shows that the extent of wound healing offered by the wound dressings was 50% faster than commercial wound dressing. 5. Curcuma longa (turmeric) - The wound-healing activity of turmeric is due to the presence of curcumin. - Curcumin is the major constituent of plant C. longa. Its major constituents are curcuminoids, which are polyphenols and have several properties including antioxidant, anti‐inflammatory antitumor induction of detoxification enzymes and provide protection against degenerative diseases. - Curcumin can enhance cutaneous wound healing in rats. - Curcumin‐incorporated collagen matrix showed increased wound reduction, enhanced cell proliferation, and free‐radical scavenging activity. - Curcumin was also shown to accelerate the closure rate of punch wounds in streptozotocin (STZ) diabetic mice. - At higher concentrations, curcumin had been reported to reduce wound contraction. - In another study, curcumin‐loaded poly(ε‐caprolactone) (PCL)/gum tragacanth nanofibers were developed to repair diabetic wounds. - The presence of curcumin increased the fibroblast content and vascular density in the wounds and prevented oxidative damage to the skin. - Curcumin is nontoxic.

194

A study shows GSE‐loaded SF/PEO nanofibrous mats enhanced the proliferation of the skin fibroblasts and protected them against damage from tert‐butyl hydroperoxide‐ induced oxidative stress. 11. Green Tea - Catechins are polyphenolic compounds present in the unfermented dried leaves of the Camellia sinensis, which is a source of tea. - Green tea contains antioxidants such as carotenoids, tocopherols (vitamin E), and vitamin C. - Green tea prevents the nanofiber from sticking to the wound surface. 12. Mangostem - The film containing mangosteen is found to improve antimicrobial activity and is also noncytotoxic. - Cumulative release of the extract was found to be 30.30% to 48.80% after 60 hours - Study showed that the presence of teak leaves methanolic extract improves the cell migration rate of fibroblast. 13. Biophytum sensitivum - The cells showed greater than 70% of viability for the BS-loaded PCL fibres after 24‐hour exposure to the cells. - N.B. The paper contains a table mentioning the biomedical activities of some of the herb‐derived compounds‐incorporated wound dressings -

-

-

-

-

-

-

Anti-microbial agents

1. Silver is characterized by several modes of action, comprising disruptions of bacteria cell walls, inactivation of bacterial enzymes and interference with the synthesis of bacterial DNA. 2. Iodine has been also widely employed as an antiseptic agent since the first demonstrations of its anti-microbial properties. 3. Antibiotics represent another strategy to strongly face infections and they have become particularly popular with the introduction of in situ delivering systems. Indeed, this mode of administration has led to a remarkable reduction in the required dosages

Medicated wound dressings -

Wound dressings releasing antibacterial agents are made by adding antimicrobial agents to wound dressings during the production process. Pain is a common problem affecting all patients suffering from chronic skin wounds. Moreover, pain-related stresses weaken the immune system response, thus leading to delayed wound healing. Physical trauma can produce pain, but it can also be generated by dressing changes, debriding, wound cleaning, and a protracted inflammatory reaction. Hence, together with infections, pain management is another important issue to face to improve patients’ quality of life. With the aim of developing wound dressings capable of more actively participating in the wound healing process, more recently the attention has been focused on the investigation of the role exerted by released biological factors.

Bioactive dressings are wound dressings constituted by precursors showing endogenous activity that may be used to actively accelerate tissue regeneration.

195

compared to intravenous or oral administration routes.

In summary, the process of wound healing is not static. It requires an appropriate environment at each stage of the healing process, and a reasonable approach to the selection of dressing for certain types of wounds should be clarified for clinical professionals. An ideal dressing is expected to possess the capacity for moisture balance, promote oxygen exchange, isolate proteases, stimulate growth factors, prevent infection, facilitate autolytic debridement, and promote the production of granulation tissue and reepithelialization. However, currently, there are no dressings that can achieve all these functions. Hence, the specific selection of modern wound dressings for different wounds should be based on particular conditions, such as the patient's primary disease, the characteristics of the dressing, and especially the physiological mechanisms of wounds. This chapter summarized the characteristics of various wound dressings and their applications in different wounds, aiming to provide a clinical guideline for the selection of suitable wound dressings for effective wound healing

Wound dressings releasing antiinflammatory drugs

-

1. Ibuprofen 2. Lidocaine 3. Opioids They are the most exploited antiinflammatory and analgesic drugs for the treatment of chronic wounds and, thus, they are widely investigated by researchers.

Wound dressings embedding biological factors -

Among them, growth factors (GFs) are bio-macromolecules physiologically involved in the wound-healing pathway as they mediate the interactions between cells and the local environment.

Advanced wound dressings -

Advanced wound dressings refer to a class of smart systems able to release their payload in response to external stimuli, such as temperature, pH, oxygen and moisture composition, with the aim to further increase their therapeutic efficacy while reducing the released dosages.

196

Pictures Chapter 4

Figure Examples of dressings/absorptive wound dressings. There are dressings that are able to handle considerable amounts of exudate (Panels A and B). The photograph shows a small sample of hydrocolloids, foams, and calcium alginate. There are many variations of these dressings, and they keep evolving. Although there is substantial experimental evidence that moisture-retensive dressings are capable of accelerating the healing of partial thickness wounds, there is no absolute evidence that they achieve complete wound closure in full thickness wounds. However, they are very useful in pain relief, autolytic debridement, and stimulation of granulation tissue. Hydrocolloids can also block bacteria from entering the wound bed.

197

Figure Choosing a wound dressing/dressing dry skin in an exudative wound. Panels A and B show the use of a primary dressing (bismuth/petrolatum impregnated gauze; Panel A) and the use of an absorbent secondary dressing (Panel B), respectively. The patient had a large venous ulcer that was complicated by the presence of severe dermatitis.

198

Figure Choosing a wound dressing/difficult locations. At times, the location of the ulcer makes it very difficult to apply certain dressings. A dressing we have found to be helpful in these circumstances is this hydrocolloid dressing with paper tape “wings.” Panel A shows this dressing being applied to this foot ulcer just above her heel. In Panel B the hydrocolloid portion of the dressing is over the ulcer. Rings of foam on the outside act as a protective barrier. One can remove as many of these rings as needed based on the size of the ulcer.

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Gauze dressing:

Figure Wound contact (primary) dressings. These are all examples of primary dressings. Going horizontally from top to bottom, the left upper dressing is a meshed gauze impregnated with petrolatum and 3% bismuth. The upper middle dressing is a soft fenestrated, net-like silicone dressing, which allows wound fluid to escape and decreases the need for painful dressing changes. The large dressing on the right is a nonadherent knitted viscose rayon material that allows free passage of exudate. The left lower dressing is a soft sterile cellulose material impregnated with ionic silver. The bottom middle dressing is a thin cotton nonadherent pad. While these dressings and others are labeled as being “non adherent,” they still adhere to the exudative wound and commonly cause dressing removal injury to the thin migrating epithelium.

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Film dressing:

Figure Film dressings. These polyurethane dressings are generally transparent and adhere to the skin surrounding the ulceration. They are very good for shallow wounds with little exudate. Only a handful are shown in this photograph, and each brand will have its own specific advantages or special indications. They also vary in terms of permeability.

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Foam dressing:

https://www.google.com/search?q=foam+dressing&tbm=isch&ved=2ahUKEwjmvHm6Kb6AhXOnaQKHQI9CDkQ2cCegQIABAA&oq=foam+dressing&gs_lcp=CgNpbWcQAzIECAAQQzIFCAAQgAQyBggAEB4QBzIG CAAQHhAHMgYIABAeEAcyBggAEB4QBzIGCAAQHhAHMgYIABAeEAcyBggAEB4QBzIGCAAQ HhAHUN0MWIoaYJQmaABwAHgAgAH_AogB1weSAQcwLjQuMC4xmAEAoAEBqgELZ3dzLXdpe i1pbWfAAQE&sclient=img&ei=uIArY-a-E867kgWCqDIAw&bih=657&biw=1366&rlz=1C1FHFK_enEG938EG938#imgrc=99AiUBUyvWx83M&imgdii=9ckrvyflE 1frxM

202

Figure Example of localized supplemental pressure using foam. We use localized supplemental pressure when the ulcer is not healing, irrespective of its location. This 59-year-old woman has a venous ulcer that has not developed good granulation tissue and is not healing (Panel A). Frequent surgical debridements have been required. Panel B shows the application of a foam dressing insert directly over the wound (extra gauze or foam can be added), which will be followed by the application of compression bandages.

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Hydrocolloid dressing:

Figure Ulcers after surgical arterial reconstruction/ follow-up. His blood flow was adequate and good wound care should enable these ulcers to heal. He was treated with hydrocolloid dressings. A few months later, he was completely healed. We have seen many patients develop ulcers after surgical reconstruction, particularly within the surgical excisions. Often, conservative therapy or small and thin autologous grafts can help the situation.

204

Figure Securing a hydrocolloid dressing in place. It is extremely useful to hold down the dressing and its borders when applying a hydrocolloid dressing. Sometimes, it is helpful for the clinician to keep his or her hand over the dressing for almost a minute; this helps in warming the material and securing it to the wound. Rounding the edges of the dressing with scissors prior to application makes it less likely that the originally sharper edges of the dressing will be stuck onto the secondary dressing and come off unintentionally upon dressing removal.

205

Figure Proper hydrocolloid removal. Depending on whether the patient is ambulatory or not, it is wise to have a rather extensive border of the dressing on the side that is most dependent, in order to minimize leakage of exudate and dressing removals. These four panels show the appearance and removal of a thin hydrocolloid dressing 3 days after it was applied to a venous ulcer. Panel A shows that the patient has been mostly in a recumbent position, for the exudate is tracking down posteriorly. As mentioned earlier, the best way to remove these adherent dressings and minimize damage to the healing structures is to lift up the dressing as a sheet and not to roll it back (Panel B). It seems anti-intuitive, but it has been shown to generate less damage to the wound. This movement is slowly continued throughout the process of dressing removal (Panel C). At the end, once the nonulcerated skin has been reached, the dressing can be slowly rolled back (Panel D).

206

Hydrogel dressing:

Figure Choosing a wound dressing/relieving pain. This illustrates the application of a hydrogel dressing (Panels A and B). Panel A shows the polyurethane covering on one side (which will be in contact with the wound bed) being removed. It is easy to minimize the clinical significance of the shallow wound seen in Panel B. However, such small wounds (in this case from livedoid vasculitis) are very painful. The vasculitic component is suggested by the purple areas and hyperpigmentation. Gel dressings can be quite effective in relieving pain in these types of ulcers. Panel B shows the coverage of the wound with the hydrogel dressing. At this point the outer polyurethane fi lm has not been removed yet and may remain in place to prevent drying of the gel dressing.

207

Figure Choosing a wound dressing/radiation injury. This man had a liver transplant and required multiple fluoroscopic exams. Although this is not commonly known, repeated or prolonged exposure to fluoroscopy can cause serious radiation injury. This painful wound developed in the midst of the area affected by the radiation. The tissue around the wound is fibrotic and shows telangiectasia (Panel A). These types of indurated plaques are commonly mistaken for the morphea variant of localized scleroderma. The ulcer itself has a poor wound bed, even after several attempts at surgical debridement. There were two problems in choosing a dressing for this wound. One is that the wound was on the back, thus a nonadherent dressing would have to be taped in place. The second problem was that tape or strongly adherent dressings could further damage the atrophic surrounding skin. In this case, an island hydrogel was used (Panel B) because it has an adherent border that allows easier removal. At the same time, the hydrogel provides pain relief. It is transparent, thus allowing wound inspection without removal. Moreover, the grid on the dressing can be useful for wound measurement.

208

Figure shows a wound abrasion treated with povidone iodine after 7 days. The wound abrasion showed scar formation, however, the granulation was evident. The skin was color pink and moist even if the scar reveals a collagenous epithelialization. Abrasions can use povidone iodine [4, 6] however; it is expected to have scar tissue formations. RIII Dioso, K Judenimal, G Arunaj - Journal for Research| Volume, 2017 - academia.edu

209

Figure likewise is treated with normal saline because the laceration from exit sites shows Evidences of necrosis outside the wound perimeter. Normal saline dressing solutions are more likely indicated to wounds with exit site necrosis [7] because it allows moisture and ensures that blood vessels remain intact. Daily treating the wound with normal saline religiously for more than 10 days allows skin integrity to remain intact. The wound returned to its moisture hence, nutrients again were redistributed by the blood vessels in order to re-epithelialize thus granulate and makes the skin more intact. RIII Dioso, K Judenimal, G Arunaj - Journal for Research| Volume, 2017 - academia.edu

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Figure on the other hand shows the effectiveness of using normal saline However, on abrasions. The wound maintained its vascularization and ensure that the integrity of the epithelium remained moist in 5 days. There are lesser episodes of scar formation and the tissues remain intact. The granulation looks pinker in color after treatment with normal saline and it does not lead to necrosis. Fallahil et al [5] agreed that normal saline solution as wet-to-dry dressing applied on abrasions and wound dehiscence can preserve the integrity of the skin and its surrounding epithelium thus maintains its moisture. RIII Dioso, K Judenimal, G Arunaj - Journal for Research| Volume, 2017 - academia.edu

211

Figure Various wound dressings that deliver silver to the wound. Silver dressings come in several concentrations of this antimicrobial, different forms and sizes of the sheets, and in different materials such as foams, calcium alginates, and hydrofibers. These dressings can provide a sustained release of silver (even in nanoparticle technology) to the wounds, and are able to absorb exudate. In relatively dry wounds, silver dressings may be moistened with sterile water to facilitate transfer of silver into the wound bed. Silver dressings are generally well tolerated by patients, and allergic contact dermatitis to silver is rare. The dressing material into which silver is incorporated consists of single/multiple and combinations of rayon, polyester, and polyethylene. Silver delivery to the wound can take place within minutes of the application.

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Figure Use of a silver-delivery dressing. Dressings capable of delivering silver for its antimicrobial properties come in different and often complex configurations. They can consist of polyester, rayon, polyethylene, and combinations. The silver component is generally coated on one side of the dressing. When wounds are dry, the dressing needs to be saturated with sterile water for effective delivery of the silver. Panel A shows one such dressing over a layer of gauze and which has already been saturated with sterile water and is ready for application. Panel B illustrates how these dressings can be cut to conform more easily to the size of the wound.

213

Figure Cadexomer iodine dressings. Shown here are two types of iodine-containing dressings. In a cadexomer (microbeads) vehicle, cadexomer iodine is available as a sheet (right side of Panel A) or as an ointment (Panel B). The sheet form of this dressing has the advantage of not containing polypropylene glycol and thus is less irritating. The ointment form in Panel B, which can generally be applied to other support dressings, does contain polypropylene glycol and can be quite irritating and cause burning on application. For this reason, the cadexomer iodine ointment must be applied very sparingly to the wound. These dressings are used in exudative wounds and exchange iodine for wound exudate. One gram of the cadexomer iodine can absorb up to 6 g of fluid. The dressings facilitate autolytic debridement. A relative contraindication for use is allergy to iodine, the presence of severe thyroid disease, or the concomitant systemic use of lithium.

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Figure Cadexomer iodine application. When indicated, there are several nonsurgical ways to debride wounds and stimulate granulation tissue, besides the use of moisture-retentive dressings. Here we have used cadexomer iodine ointment. This preparation consists of 0.9% iodine incorporated into cadexomer beads. When this agent is applied to an exudative wound, the iodine within the microscopic beads is slowly exchanged for wound fluid and released into the wound. Cadexomer iodine ointment is usually applied by spreading a very thin layer of it on a minimally adherent dressing (Panel A). Only enough cadexomer iodine to cover the wound area should be used. The iodine is slowly released into the exudative wound, and the ointment becomes a light brown color as shown here (Panel B). This is a signal for removal of the material and, if needed, a new application. From a practical standpoint, it is probably easier to instruct the patient or the visiting nurse to remove cadexomer iodine and reapply it daily, rather than waiting for this change in color. Also, we have found that dried cadexomer iodine is more difficult to remove.

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CHAPTER

5 Omnia Alaa El-Din Abd El-Salam, Omnia Hussein Ibrahim, Nada Metwally Mohamed, Ibrahim Ahmed Elsherbini

Natural Polymers In Wound Dressing Various fabrication methods and biomaterials have been explored to produce dressings.

Polymeric dressing materials -

-

-

-

-

-

Significant progress has been made, in particular, in the search for a flexible biomaterial that is biocompatible, nonimmunogenic, readily available, and has tunable properties. In this regard, a variety of synthetic and/or natural polymers have been investigated. The biomaterials in wound healing can serve two different functions: 1. They have the capacity to serve as supporting frameworks for endogenous cells to adhere to, move to, secrete growth factors from, and finally integrate into the skin tissue. 2. Provide mechanical protection, keep the environment moist, and stop the bacterial invasion to perform a passive function. A variety of biomaterials have been transformed into formulations for wound healing, including sponges, hydrogels, foams, fibres, composites, and particles. By physically or chemically crosslinking soluble polymers, hydrogels are incredibly hydrophilic macromolecular networks. Hydrogels are exceptional possibilities for biomedical applications because of their peculiar characteristics, which include great sensitivity to physiological conditions,

-

-

-

216

hydrophilicity, soft tissue-like water content, and sufficient flexibility. Hydrogels can respond to specific environmental stimuli, such as temperature, pH, and ionic strength, by swelling and contracting water in a reversible manner. As a result, hydrogels' intelligent physiological reaction to changes in physiological variables points to a variety of medicinal applications for them. Its structure enables the transportation of bioactive molecules, which can be swapped with absorbing wound exudates during the sustained release phase after connecting hydrogels with the wound surface. Bioactive molecules can be entrapped into hydrogel networks during the gelling process. We can categorise the various types of contemporary wound dressing based on a variety of quantifiable factors as follows:

Hydrogel classification Measurable factors Source

Polyemer composition

Natural polymer e.g. (Alginate,c ollagen) Synthetic polymer e.g. (Polyvinyl alcohol)

Homo-polymeric e.g.(PolyNisopropyl acrylamide Hetero-polyameric e.g.(Polyvinyl alcoholgelatin) co-polymeric e.g.(PolyPEGMA-comonomethyl itaconate Hyprid (Different polymers or phases) Composites (Organic and inorganic components as fibers and nanoparticles Interpenetrating polymer networks (IPNs) e.g.(Polybinyl alcoholalginateIPN)

Network structure

Sensitivity to stimuli

Physical crosslinking e.g.(Freezethawing) Chemical crosslinking e.g.(Glutaraldeh yde)

Physical stimulus e.g.(Temperature) Chemical stimulus e.g.(PH, ionic, strength Bio-chemical stimlus e.g. (Antigen, enzyme)

Physical aspect

Configiuration of chains

Micro/nanoparticle e.g.(Microbed/nanogel) Film e.g. (Electrospun mat) Matrix e.g.(Scaffold) Gel (Injectable drug oadedhydrogrel

Non-crystalline (Random arrangement as amorphous domain) Semi-crystallin (Amorphous + drystalline domains

Charge of polymer networks

Non-ionic e.g(No change) ionic e.g.(Cationc or anionic) Zwitterion e.g. (Both cationic and anionic Amphoteric e.g.(Both acidic and basic groups)

Classification according to the source of polymer Proteins & Peptides Polysaccharide

Natural

Proteoglycans Polycaprolactone

Bio Polymers

Polyvinylpyrrolidone Poly(lactide-co-glycolide)

Synthetic Polyethylene glycol Polyvinyl alcohol Polyurethanes Collagen Proteins and peptides

Gelatin Pectin & gums Cellulose Dextran

Neutral

Beta glucans Natural Polymers

Polysaccharide

Acid Basic

Alignates Hyaluronic Chitin Chistosan Fucoidan

Proteoglycans

Sulphated Glycosaminoglycans

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Chondrotin Heparin Keratin

General characteristics

Natural polymers

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Definition and sources

Has a rapid rate of biodegradation and breaks down quickly when in contact with exudates. - Outstanding biocompatibility, outstanding biodegradability, nontoxicity, and demonstrated clinical safety - It has functional groups that can be changed, making it simple to alter with various polymers and medications. - Can be mass-produced via microorganisms using sucrose. - Has a lengthy history of use in various biomedical fields. As an ophthalmic solution, drug carrier, and tissue protectant in organ transplantation, for instance. - Recently, dextran has found application in tissue engineering applications. - Dextran has been demonstrated to function as a synthetic niche for cell culture and differentiation. - Dextran can promote tissue repair via various mechanisms. 1- Encourage angiogenesis and guard against ischaemic damage to skin tissue. 2- The proangiogenic activity of dextran can facilitate the development of granulation tissue during the wound healing process. 3- Induce collagen deposition and modulate the tissue remodelling phase.

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Natural polymers are macromolecule compounds found in animals or plants that are created by photosynthesis or other biochemical processes in the environment.

1. Cellulose Definition and sources -

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The most prevalent polymer in nature. Can be produced from a variety of sources, including bacterial species and plant cell walls. It is possible to incorporate montmorillonite and silver nanoparticles into the cellulose matrix produced by bacteria, which exhibited strong antibacterial activity against Gram-positive and Gram-negative bacteria.

General characteristics -

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Cellulose-based biomaterials can be processed using a variety of solvent systems and have high mechanical strength. They do not easily lose their structural integrity upon applying on high exudate wounds. Their nanofibrous wound dressing is highly biocompatible.

2. Dextran

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Dextran is a bacterial polysaccharide made up of D-glucopyranose residues that are 1,6-linked. In the past, dextran was used as a blood plasma polymer expander and for drug delivery.

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The ability to retain moisture may cause wound maceration. Dextran's bioactivity is insufficient to trigger a wound-healing response that works. Therefore, recent research has concentrated on adding different

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General characteristics

bioactive agents to the dextran-based scaffolds' matrix. They found that compared to pure polymeric hydrogels, growth factorloaded hydrogels had higher proliferative and healing functions. The level of oxidative stress in chronic wounds is significantly higher than dextran's antioxidant capacity. Antioxidant medications could therefore be incorporated into its structure as a possible solution to this problem.

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3. Chitin derivatives and chitosan: Definition and sources -

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N-acetyl-D-glucosamine and Nglucosamine units are distributed in block or random form throughout biopolymer chains to form the copolymer polysaccharide known as chitin. Chitin is a biological substance that can be easily and cheaply obtained from the cell walls of fungi and the skeletons of invertebrates. Derived from crustacean shells, which are byproducts of the seafood processing industry, after demineralization and deproteinization processes. The processing of seafood generates a significant amount of waste each year. Crustacean bodies contain about 75% byproducts as total body mass. As a result, the removal of chitin and other valuable materials from crustacean waste is a substitute that can lessen waste and is a crucial step in the production of useful compounds with significant biological properties and applications in a variety of fields. Chitosan is the partially- to fullydeacetylated form of chitin.

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Due to its antibacterial qualities, hemostatic function, biocompatibility, non-immunogenicity, and excellent oxygen permeability, this biomaterial has become more therapeutically appealing in wound healing. It also promotes wound granulation, making it a candidate for use as an accelerator agent in the treatment of deep and open wounds. Chitosan can bind to negatively charged cell plasma membranes and increase the permeation of various drugs because it has a net positive charge; Chitosan was manufactured in a variety of forms, including films, hydrogels, fibres, powders, and nanoparticles, for use as a wound dressing. The cost and handling challenges of chitosan, a common ingredient in dressings, are a drawback.

4. Pullulan -

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It is a biomaterial made of polysaccharides that are produced by the bacterium Aureobasidium pullulans. This biomaterial has a high capacity for absorbing water, antibacterial activity, and wound healing capabilities.

5. Hyaluronic acid or hyaluronan Definition, sources -

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Hyaluronic acid is a naturally occurring biodegradable biopolymer that is made up of D-glucuronic acid and D-N-acetylglucosamine and is highly abundant in natural ECM.

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It was derived from bond and connective tissues of mammals and synovial fluids. Since its discovery in 1934, it has been widely applied in cartilage and tissue repair.

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HA-based hydrogel wound dressings stand out because they can be used to treat wounds at all four stages of the healing process, aren't abrasive or reactive to biological tissue, and are permeable to metabolites. They are used particularly for ophthalmological purposes, HA film-like dressings exhibit desirable qualities because they allow the transmission of oxygen, carbon dioxide, and water vapour. The demonstrated ability of HA to decrease bacterial adhesion and biofilm formation in various contexts is associated with its capacity to inhibit microbial attack during wound healing; HA is not bactericidal, but rather bacteriostatic. It has been demonstrated that HA exhibits the greatest bacteriostatic effect against S. epidermidis and P. aeruginosa when compared to other biomaterials with bacteriostatic properties, including collagen, hydroxyapatite, HA, and PLGA. HA molecules also form a random network of chains that can act as a sieve, preventing the spread of bacteria. Hyaluronan interacts with the majority of tissue constituents, including proteins and growth factors, which speeds up the healing process for most wound types and promotes tissue repair. Hyaluronic acid in sheets can help in angiogenesis and convert injured areas

of the chronic wound into the acute wound. Additionally, they are thin, elastic, transparent, and generally used in conjunction with hydrogels. Films, however, are typically not appropriate for wounds that are actively exuding, being initially inserted between injured tissues to lessen the severity of abdominal adhesions.

6. Collagen: Definition and sources: -

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Collagen type-I, a biocompatible abundant protein found in the body's connective tissues, is one of the first, oldest, and most frequently used dressings to date. While collagen has not yet been used as a wound dressing membrane, various collagen forms, such as suspensions, foams, wound dressing materials, sutures, sponges, and gels, have been used in literature for dermal injections.

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Biodegradable collagen type-I membranes have recently been used for children's superficial partial thickness burns and burns/chronic wounds requiring surgical defects of the oral mucosa. Collagen is essential for haemostasis, which aids in the wound-healing process. It also directly supports keratinocyte migration and fibroblast growth. Hyaluronic acid, for example, and collagen have been combined as dressing membranes, skin regenerative templates, and skin substitute matrices. The common disadvantage of collagen membranes usage is, they have a big

Advantage and disadvantage

permeable to bacteria and microorganisms.

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7. Alginic acid and sodium alginate: Definition and sources -

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Alginate, a naturally occurring polymer derived from brown algae, is one of the most representative and extensively researched natural polymers.

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Advantage and disadvantage -

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Alginate's benefits include affordability, good biocompatibility, low toxicity, and simple crosslinking. Alginate hydrogel can be used in tissue engineering, cell migration, and wound healing because of its similar structural makeup to the extracellular matrix found in natural tissues. Alginate hydrogel wound dressings have excellent hygroscopic and antibacterial properties, which could keep the wound environment moist and sterile while speeding up the healing process. A promising research area in precision medicine is the use of Alginate microcapsules or fibres to deliver various loads, such as small molecules of drugs and proteins, to particular cells. Pure alginate hydrogel, however, has very poor mechanical properties. A fracture develops when a material is stretched to an estimated 1.2 times its original length.

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Definition, sources and usage

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Gelatin is obtained by an incomplete denaturalization of collagen extracted from the boiling of some materials such as bones (27%), connective tissues or organs (28%), and skin of certain animals (44%, usually cows and pigs). Since gelatin comes from nature, it has biological properties and a history of use in biomedical applications. In the past, gelatin was used to create transparent films with glucan and strong hydrogel membranes. Additionally, gelatin and PVA were physically combined to create hydrogel membranes containing glutaminase for use as wound dressings. These membranes were then crosslinked enzymatically and then through F-T crosslinking cycles.

10. Konjac glucomannan (KGM)

8. Glucan

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Glucan films exhibit strong antiviral, antibacterial, and anti-inflammatory effects. Glucan is regarded as a crucial healing agent additive and an accelerator for the rate of healing in dressings for deep and superficial wounds.

Glucan is a water-soluble biodegradable polymer derived from the fermentation of incubated plants. It consists of β-(1-3) and β-(1-6) linked-D-glucose residues.

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It is a kind of plant polysaccharide with good cell compatibility and gel properties. Due to its exceptional ability to absorb and retain water, KGM—a soluble natural bio-polysaccharide—is the preferred biological matrix material and has been extensively studied and used in wound dressings. The range of applications for KGM in the creation of biodegradable membranes, enzyme-embedded biomaterials, and drug delivery

systems can be increased by optimising the structure of the substance.

Synthetic polymers

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1. Polyurethane -

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Professor Dr Otto Bayer developed polyurethanes in the 1930s (19021982). Polymerization reactions involving the conjugation of diol and diisocyanate groups result in copolymers known as polyurethane. There are numerous varieties of polyurethanes, and they differ greatly in appearance and texture. They are utilised in a wide range of goods, including coatings, adhesives, mattresses, foam insulation, and shoe soles. However, each type's fundamental chemistry is essentially the same.

4. Poly(N-vinylpyrrolidone) (PVP) -

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2. Poly (methyl methacrylate) -

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Methyl methacrylate is a synthetic, non-biodegradable polymer that serves as an anti-heat and anti-UV substance. As a result, it has been used as a supporting dressing material in surgical plastic, dental tissue, and the treatment of minor injuries. This polymer has not been reported as a direct wound dressing membrane yet.

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3. Proplast or Alloplastics -

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because they are non-carcinogenic, easily sterilizable, insoluble in polar or non-polar solvents, and inert materials. To hasten the healing of the epidermis and epithelium layers, alloplastic copolymers from polyetherpolyesterhydroxyapatite composite tympanic membranes were created and implanted.

PVP is a water-soluble and biocompatible/biodegradable synthetic polymer. Due to its low toxicity, good water vapour transmission, and bacterial impermeability, it has previously been used as hydrogel membranes for skin substitutes. A crosslinked PVP hydrogel membrane produced by radiation polymerization demonstrated very high elasticity and an impermeable response to bacterial invasion. Cell attachment tests, however, revealed that PVP membranes are best suited for healthy or damaged skin in tropical environments. Additionally, they demonstrated that adding PEG reduced the bacterial barrier and improved the porosity of PVP hydrogel membranes for good water vapour transmission. 5. Polyethylene glycol (PEG)

Low-density polyethylene, polydimethylsiloxane, polyethylene terephthalate, and Teflon (polytetrafluoroethylene) are examples of high biocompatible synthetic polymers known as proplast or alloplastic. These materials were first used as a substitute for autologous tissues in surgery. These polymers are the best synthetic dressings, especially for injured areas

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PEG is a water-soluble synthetic viscous amphiphilic polymer. It is a good candidate for many medical applications because of its biological features, which include nontoxicity, biocompatibility/ biodegradability, transparency, and cost-effectiveness.

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PVA-PEG-CaCl2 hydrogel membranes for wound dressing have been crosslinked by γ-irradiation. CaCl2 solution was used as a plasticizer and gelling agent to enhance the synergistic effect of dressing membranes, and PEG was added to increase thermal stability. This kind of membrane introduced beneficial biological properties, such as no inhibition of cell proliferation, while PEG accelerated the size and rate of wound healing.

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6. Poly(N-isopropylacrylamide) (PNIPAm) -

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N-isopropylacrylamide is a watersoluble monomer that can expand and contract at 32oC below and above the low critical solution temperature (LCST), respectively. Its polymer is a thermally reversible polymer with a low critical solution temperature in water. Since PNIPAm has other biological properties like being nontoxic, biocompatible/biodegradable, and physiologically responsive, it has received a lot of attention for use under physiological conditions. Utilizing an electrospinning technique, PVA-PNIPAm-levothyroxine (T4) nanofibrous mats were created for advanced wound dressing applications, such as reducing adipose tissue deposits on the skin. They concluded that PNIPAm content increased the sustained release of T4 from mats. Furthermore, PVA-PNIPAm blend nanofibrous mats are preserved on T4, compared to PNIPAm containing T4. All of these polysaccharides may be useful in the treatment of wounds, but none of these polymers can completely

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satisfy the requirements for an ideal biomaterial. A successful wound dressing biomaterial should be composed of various biomaterials with complementary functions, just as ECM is made up of different polymers. A composite of dextran and chitosan, for example, has been shown to effectively stop bacterial growth and migration despite dextran's lack of significant antibacterial activity. - The majority of polymeric dressing materials, including alginates, hydrogels, foams, films, and hydrocolloids, have the aforementioned benefits. However, hydrogels are said to be the best option when compared to other types of dressings because they meet the criteria for ideal wound dressings. Excellent biocompatibility and biodegradability of hydrogels made from natural polymer materials is a major advantage in biomedical research fields like tissue engineering, drug delivery, bio-sensing, disease treatment, and wound dressing. Hydrogels' only drawback is a lack of mechanical stability when swollen. The use of "composite or hybrid hydrogel membranes," a system made up of multiple polymers in the dressing composition, has been used to address this drawback. Hydrogels are typically stabilised using a process known as crosslinking, which involves chemical or physical interactions between the polymer chains. Hydrogels have the capacity to retain a significant amount of absorbed water in their mesh structure after crosslinking. In situ hydrogel formation using physical or radiation crosslinking is

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preferred to chemical crosslinking, especially for biomedical applications. When compared to the second crosslinking method, the physical method avoids the use of crosslinking agents, organic solvents, and chemical reagents, which resolves the toxicity issue. The safest crosslinking method for hydrogel formation is thus physical crosslinking, which is typically used for wound dressings and in-situ crosslinking cases. Examples of physical crosslinking include hydrogen bonding, Van der Waals bonds, or freeze-thawing consecutive cycles.

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STUDIES ABOUT WOUND DRESSING MANUFACTURED FROM NATURAL POLYMERS

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Microfluidic fabrication of calcium alginate helical microfibers for highly stretchable wound dressing -

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Alginate hydrogel has excellent qualities that make it suitable for use as a dressing for wounds. Pure alginate hydrogel, however, has very poor mechanical properties. A fracture develops when a material is stretched to an estimated 1.2 times its original length. Therefore, pure alginate hydrogel is unacceptable for applications requiring a greater degree of flexibility and stretchability, such as joints’ wound dressings, and must undergo specific processing or be combined with other polymer materials to address the shortcomings. Making double network (DN) hydrogels, nanocomposite hydrogels, or modifying natural polymers chemically before cross-linking are a few of the methods that have been used

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to enhance the mechanical properties of natural polymers. Nevertheless, there are issues with (DN) hydrogels and nanocomposite hydrogels techniques. Firstly, these two techniques increase the cost and complicate the normally simple and inexpensive preparation process for natural polymer hydrogels, which prevents their widespread practical application. Secondly, DN hydrogels will lose the advantage of having a structure similar to the extracellular matrix of biological tissues, which will restrict further applications in the biomedical field. Alginate hydrogels, however, retain this advantage. As a result, it is still possible to modify the mechanical properties of polymers more straightforwardly. The addition of a helical shape enhances the stretchability and flexibility of calcium alginate hydrogels without altering their network structure. A composite polymer film with high elasticity, high transparency, and controlled release ability was created by fixing the calcium alginate helical fibres in polyacrylamide (PAM). This film has potential use in the field of biomedicine, particularly in joint wound dressings. Helicoidal calcium alginate fibres were spun using a two-phase microfluidic channel with a coaxial structure. The inner phase contained a solution of sodium alginate, and the outer phase contained a solution of calcium chloride. The sodium alginate solution solidified to form fibres after contact. The calcium alginate fibres could be folded into spiral shapes and maintained this morphology

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throughout the process at an appropriate flow rate. When compared to other techniques for preparing helical fibres, the microfluidic method is simple to use and doesn't call for expensive equipment. Another benefit of this type of dressing is that it is transparent, making it possible to see the state of the wound beneath it without the need for replacement. This transparency not only makes it easier to assess the wound but also lowers costs and patient discomfort.

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Conclusion Advantages of calcium alginate/PAM composite polymer membrane as a wound dressing:

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1. Has very good elasticity and stretchability. 2. High transparency and good skin adhesion. 3. Could achieve slow release of loaded substances. 4. Offered excellent application prospects in the field of dressings for joint wounds.

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Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin

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In this study, a composite made of alginate, gelatin and borax is performed. -

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In the presence of borax, periodateoxidized alginate quickly crosslinks proteins like gelatin to produce nontoxic, biodegradable hydrogels in situ. The composite matrix is a potential material for a wound dressing because it possesses the hemostatic properties of gelatin, the wound healing-

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promoting properties of alginate, and the antiseptic properties of borax. It was discovered that the hydrogel had a fluid uptake of 90% of its weight, which would stop exudates from building up in the wound bed. The hydrogel's water vapour transmission rate (WVTR), which was discovered to be 26867124 g/m2/day, suggests that it can keep the wound bed moist in moderate to heavily exuding wounds, which would facilitate epithelial cell migration during the healing process. Spray-on films have been around since the 1950s, but when applied to thirddegree open wounds, it was said to cause bacterial spread issues. "Hydron" is a commercial dressing made of poly (2-hydroxyethyl methacrylate) and polyethylene glycol that is formed on the wound in situ by spraying. However, their high cost prevents them from being used as frequently as more affordable dressings. A recent study found that the formation of in situ hydrogels was accelerated by the presence of small concentrations of borax in the periodate-oxidized alginate/gelatin reaction. According to some reports, certain alginate dressings, like Kaltostat, can speed up the healing process by inducing human monocytes to produce more a-interleukin-6 and other tumour necrosis factors. The proinflammatory stimulus produced by the production of these cytokines at the wound site is beneficial for wound healing. The presence of endotoxin in alginates is thought to be the cause of the high level of bioactivity of these dressings.

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Gelatin sponges are used for inducing haemostasis in bleeding wounds. As a result, a composite matrix made of gelatin and alginate will have the synergistic advantages of both polymers. Borax has a long history of use in medicine due to its antiviral and antiseptic properties. It has been reported that a physiological amount of dietary boron has a positive impact on a number of metabolic processes. Dietary boron acts as a signal suppressor to reduce certain enzymatic activities that are typically upregulated during inflammation, which helps to control the normal inflammatory process. It is evident from these studies that when exposed to air under dry conditions for an extended period of time, the material will lose its water content. These dressings will therefore be more helpful for moderately exuding wounds than for dry wounds. It should be noted that because these hydrogels quickly absorb water, the dressings can be kept moist if desired by misting them with saline or water. According to reports, when applied to exuding wounds, this water loss enables the gel to actively move exudates and oedema fluid from the wound into the dressing. Adding medications or growth factors can boost the ability of these in situforming hydrogels to heal wounds.

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2. Chitosan Chitosan as a Wound Dressing Starting Material: Antimicrobial -

Natural antimicrobial agents are more affordable, biocompatible, and non-toxic than traditional synthetic antibiotics. In order to combat the emerging bacterial resistance, optimizations of currently available molecules or combinations of various compounds are used, as new classes of antibiotics have not been discovered since the 1980s' daptomycin and linezolid. A contemporary strategy to combat antimicrobial resistance would be to use alternative antimicrobials, such as synthetic or natural compounds, or to find newer targets. Antimicrobial polymers are considered the new generation of antimicrobials. The most promising of these polymers is chitosan, which also includes antimicrobial peptides, halogen-containing polymers, Phosphor and Sulphur derivatives, metal nanoparticles, dendrimers, heparin, polylysine, gramicidin A, quaternary ammonium polyethyleneimine, and guanylated polymethacrylate. One of the natural polymers that holds great promise for the creation of antimicrobial agents is chitosan.

Natural polymers provide a new strategy for battling bacterial infection because they are a source of antibacterial agents.

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Innate sensing of chitosan and the immune system's reaction to this polymer are still poorly understood despite published experimental data on how this polymer interacts with mammalian cells involved in wound healing processes. Polysaccharides are recognised by cell receptors and, depending on their size and structure, may trigger immune responses.

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Some of the most important factors that affect chitosan’s biomedical properties include: - Molecular weight and degree of de-acetylation. - PH effect. - Type of microorganism. - Microbial growth media components. - The source of the chitosan, and also its derivatives. The Molecular Weight and Degree of Acetylation

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The biomedical properties of chitosan are significantly influenced by its molecular weight. Chitosans are often classified as high molecular weight (HMW), medium molecular weight (MMW), and low molecular weight (LMW) According to published data, the molecular weight of chitosan affects the inhibitory mechanism that the substance has against pathogen microorganisms. As a result, nutrient uptake is inhibited by the dense layer of HMW chitosan that develops on the surface of the cell. the much smaller chitosan molecules appear to pass through the membrane and even bind to DNA and RNA. Additionally, the amount of acetylation increases the substance's solubility and positive charge, both of which have a significant impact on its antimicrobial properties. While crystallinity and biodegradability are directly proportional to the DA, solubility, viscosity, and biocompatibility tend to increase as the DA decreases.

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PH Effect The solubility of this polymer, whether in water or other commonly used solvents, has a significant impact on the beneficial properties of this polymer. The protonation of its amino groups in the presence of acid is what gives it its solubility. Since chitosan's low solubility is one of its main drawbacks, there has been an increase in interest in chemically altering this polymer to increase its solubility over the past few years. Chitosan has a positive charge and can interact electrostatically with a variety of negatively charged molecules when the pH is around 6.0. Chitosan's antimicrobial mechanism is therefore pH-dependent. According to studies, the highly positive charge on the chitosan polymer chain causes an increase in adsorption when pH levels are lowered on bacterial cell surfaces. On the other hand, chitosan will lose its charge at higher pH levels (above 6), and because its amino groups will deprotonate, it will precipitate out of the solution. Type of Microorganism: -

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Studies have shown that chitosan has a bacteriostatic and bactericidal effect, despite the fact that the exact

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mechanism of action against pathogens is not well understood. Chitosan's main, generally recognised mechanisms of action against microorganisms include the following:

negatively charged phospholipids, which results in the leakage of intracellular material. - However, this polymer appears to be unable to pass through the cell membrane in the case of chitosanresistant fungi, remaining outside the cell surface. Chitosan is unable to penetrate the cell membrane, probably due to the difference in fluidity of the cell membrane. - The plasma membrane of chitosansensitive fungi contains more polyunsaturated fatty acids than chitosan-resistant fungi, suggesting that the fluidity of membranes may play a role in how well chitosan disrupts cell membranes. - Chitosan's antimicrobial activity is correlated with the cell membrane's phospholipid fatty acid composition. - To prove this, researchers tested the antimicrobial effects of chitosan against a mutant strain of the Neurospora craasa fatty acid desaturase enzyme that was more resistant to chitosan than the wild type. 2- Interaction with Microbial DNA: - Chitosan hydrolysis products' interactions with microbial DNA make up a second mechanism that influences protein synthesis by inhibiting mRNA. - Low molecular weight chitosans have been found to have the ability to cross a cell's membrane and enter the cell. - By examining the impact of OCNPs on the electrophoretic mobility of nucleic acids, the binding of oleoyl-chitosan nanoparticles (OCNPs) to DNA/RNA was investigated. - The findings demonstrated that as OCNP concentration rose, bacterial genome interactions multiplied. By the time OCNP concentration reached 1000 mg/L, E. coli DNA and RNA migration were completely blocked.

1- Disrupting the Cell Membrane/Cell Wall: -

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Refers to the lysis of the cell membrane and the alteration of cell permeability. This effect is likely brought on by electrostatic interactions between the negatively charged cell membrane and the positively charged chitosan molecule. While Gram-negative bacteria's cell walls are strongly negatively charged as a result of the lipopolysaccharides found in the outer membrane layer, Gram-positive bacteria's cell walls are primarily made of a thick peptidoglycan layer containing teichoic acids, which give the bacterial surface a negative charge. Additionally, the fungal membrane and viral envelope, which both contain some negatively charged compounds, present a similar situation. Teichoic acids found in the cell wall of Staphylococcus aureus interact with chitosan derivatives, preventing bacterial growth up to about 100% of the time. The cell membrane of Escherichia coli was damaged by chitosan. Chitosan may also have antifungal effects on bacteria. Chitosan-sensitive fungi and chitosan-resistant fungi are two categories of microorganisms that can be distinguished in this situation. The mechanism of action in this instance differs slightly from that of bacteria. Chitosan molecules first affect the cell membrane by interacting with

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3- Chelation of Nutrients by Chitosan: - The high capacity of chitosan to chelate different metal ions (Ni2+, Zn2+, Co2+, Fe2+, Cu2+) when the pH value is higher than its pKa value may be the cause of chitosan's inhibitory effect on microbial growth. - Divalent metal cations that are advantageous to the microbial cell are attracted by both Gram-positive and Gram-negative bacterial cell wall constituents. - Teichoic acid phosphate groups, which are found in the peptidoglycan layer of Gram-positive bacteria, draw Mg2+ and Ca2+ cations in particular, maintaining membrane integrity and enzymatic activity. Lipopolysaccharides, which are found on the surfaces of Gram-negative bacteria, negatively charge the bacterial cell membrane and have a high affinity for divalent cations. - Without these divalent cations, bacteria are more vulnerable to certain chemicals and antibacterial agents. 4- Formation of a Dense Polymer Film on the Cell Surface: - High molecular mass Chitosan may accumulate and create a thick polymer film on the cell's surface, obstructing the uptake of nutrients and oxygen, which then slows the growth of aerobic bacteria. - The outer membrane's thickness prevents both the excretion of metabolic waste and the entry of nutrients into the cell. 5- Chitosan Complexes (media components): - The main goal of creating chitosan complexes with other substances is to enhance their beneficial properties, particularly their antibacterial effects, and speed up the healing of wounds.

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Different complexes between chitosan and other organic or inorganic substances have been shown in studies to enhance the antimicrobial effect and speed up the healing of wounds. Liu et al., for instance, created an antibacterial substance using the chitosan oligosaccharide-N chlorokojic acid mannich base (COS-N- MB). The resulting COS-N-MB complex had excellent inhibitory activity against pathogenic bacteria and had synergistic antibacterial effects. The adsorption to bacterial cell walls via electrostatic interactions and chelating metal ions appears to be the mechanism of action. By using an in situ deposition method to load porous chitosan/poly (vinyl alcohol) (CS/PVA) scaffolds with Ag and Se, Biswas et al. created two unique wound-dressing materials. The Se-CS complex damaged bacterial cell membranes and had no cytotoxicity toward fibroblasts, whereas the Ag-CS complex significantly inhibited bacterial growth and reduced cytotoxicity to fibroblasts. According to a study by Kaygusuz et al., cerium ion-chitosan crosslinked alginate films exhibit high mechanical resistance, flexibility, and UV protection in addition to antibacterial activity against both Gram-positive (S. Aureus) and Gram-negative (E. Coli) bacteria. Chitosan has less antibacterial activity than traditional antibiotics, but because of its unusual chemical behaviour and the presence of three reactive functional groups, this polymer can be further chemically altered to increase its antimicrobial activity.

6- The source of the chitosan, and also its derivatives. - A study contrasts the antimicrobial properties of fungal and shrimp chitosan against 12 bacterial and fungi species. - In contrast to shrimp chitosan, the results showed that fungal chitosan was more effective against P. aeruginosa, E. coli, Candida glabrata, and C. albicans. - The antimicrobial effect against the other microorganisms tested was comparable, and the MIC values were the same for both types of chitosan, showing that fungal chitosan can be a useful and suitable substitute for shrimp chitosan. - Four different types of fungal chitosan were tested, and the one that was most effective against the fungus had the lowest molecular weight and the highest deacetylation percentage (94%) (32 kDa). - There are many benefits to getting chitosan from fungi as opposed to crustaceans: 1- Get rid of harsh chemical procedures that might pollute the environment. 2- There is no chance of heavy metal contamination, and the raw material can be obtained all year long. 3- Chitosan extraction from fungus mycelia no longer requires the demineralization step. 4- By removing nitrogen, proteins, and other substances from waste, it is possible to grow fungal cultures on a variety of waste products, which helps to reduce marine pollution. 5- In addition, fungal strains can be genetically modified to produce greater quantities of chitin, which

can then be used to produce higherquality chitosan, in place of crustacean-derived chitosan. Interactions with Mammalian Cells in Wound Healing Processes: -

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Chitosan is innate, biocompatible, and non-toxic to living cells and tissue in addition to having antimicrobial and antifungal properties. Various cell types, including fibroblasts, keratinocytes, and hepatocytes, as well as myocardial and endothelial cells, have been used to test the biocompatibility of chitosan in vitro. Although wounds usually heal on their own, some people have disorders that prevent them from doing so, such as diabetics who may develop chronic, non-healing wounds that cause them to feel pain and discomfort for a very long time. In these situations, lengthy treatments are necessary, which raises the price of high-tech medical care as well. Chitosan appears to meet all of these criteria, so the focus has been on natural therapeutic substances that can quicken wound healing while also being widely available to the general public. Chitosan speeds up the inflammatory phase of the healing process by stimulating inflammatory cells, macrophages, and fibroblasts. In this way, the inflammatory phase of the wound-healing process is diminished, and the proliferative phase begins earlier. The positive charge of chitosan can be credited with both hemostatic and analgesic properties. Because it relies on electrostatic adhesion to blood cells, chitosan's special hemostatic properties are

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independent of the regular clotting cascades. Chitosan increases the expression of glycoprotein IIb/IIIa (GPIIb/IIIa), a platelet membrane receptor, and stimulates platelet aggregation and adhesion by adsorbing plasma proteins and signalling thrombin, a clotting promoter. Since 1984, when Allan et al. reported that chitosan provided a cooling and soothing effect when applied to open wounds, the analgesic effect of chitosan has been established. The wound wasn't infected, fibroplasia was significantly increased, the fibroblasts were better arranged in the newly formed tissue, and the quality of scar tissue was improved. These results came from testing the healing properties of a chitosan-alginate membrane on a cutaneous wound in rats. In addition, the inflammatory infiltrate was significantly reduced on the seventh day of treatment with the chitosan-alginate membrane, followed by a decrease in neutrophils and CD4+ lymphocytes, which may indicate a better regulation of the inflammatory stimulus by the chitosan-alginate membrane. Similarly, the chitosanalginate complex induced CD11B+ macrophage migration. These cells play a crucial role in the second phase of the healing process because they carry on the work of neutrophils by serving as growth factor reservoirs and secreting several enzymes that break down the remaining extracellular material. Chitosan might also be able to control the growth of granulation tissue and angiogenesis, ensuring proper collagen fibre deposition and enhancing the

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proper healing of damaged dermal tissue. Once it enters the body, it can be hydrolysed into an essential sugar, glucosamine, which is already present in the body, by enzymes like lysozyme found in mucus, tears, and saliva. The applications of chitosan

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The two important factors regarding the application of chitosan in wound management are: 1- Modification of the polymer. 2- Complexing it with other natural or synthetic compounds. The poor solubility of chitosan at physiological pH limits its applications, and the drug delivery process is less effective at pH levels below 6. Therefore, to overcome these drawbacks, permanent changes can be introduced into the chitosan backbone. An extremely substituted (up to 46.6%) water-soluble Ocarboxymethyl-N,N,N-trimethyl chitosan (CMTMC) that did not significantly harm human dermal fibroblasts (viability > 80% at 1 and 0.5 mg/mL). According to studies, formulations based on carboxylated and trimethylated chitosan (CMTMC) have a lot of potential for use in applications that promote wound healing. Human dermal fibroblasts were not only detoxicated by foams and hydrogels containing a high concentration of RDG (arginyl-glycylaspartic acid)-functionalized chitosan (3%) and hyaluronic acid (1.5%) but they were also encouraged to proliferate over the course of seven days and migrate.

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Additionally, combining chitosan with other organic or synthetic substances would enhance its antimicrobial effect and quicken the healing of wounds.

Asymmetric chitosan membranes prepared by dry/wet phase separation: a new type of wound dressing for controlled antibacterial release

Chitosan-based products on the market

Introduction -

There are numerous chitosan-based products on the market. 1- HemCon® dressing, a chitosan acetate bandage created as an antimicrobial dressing with hemostatic properties. 2- Chitoderm® plus is a wound dressing based on a powerful nonadhesive super absorber with a chitosan coating that has bacteriostatic action and actively promotes healing. 3- Celox™, is a hemostatic chitosanbased wound dressing that clots hypothermic blood and blood treated with blood-thinning drugs, can be easily removed from the wound site, and the residual material is naturally absorbed by the body. 4- LQD spray is used for the external treatment of chronic and acute wounds, as well as superficial and partial thickness burns. It offers physical protection, inhibits the release of pro-inflammatory cytokines, relieves pain, and has hemostatic and antibacterial properties. The US FDA (United States Food and Drug Administration) has designated chitosan as GRAS (generally recognised as safe) for wound-dressing applications as of right now.

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Laminated membranes with a porous inner layer and a dense outer layer are being researched as potential improvements over homogeneous films as wound dressing. The inner layer is intended for the drainage of wound exudates and the attachment of wound tissue, whereas the outer layer is intended for the prevention of bacterial invasion and may serve as a rate-controlling layer for water vapour permeation. Acute burn wounds have traditionally been treated with cream containing silver sulfadiazine (AgSD). However, this antibacterial cream is unable to provide long-term wound infection protection. Chitosan might work well with silver sulfadiazine to make a long-lasting antibacterial wound dressing. It has been established that the symmetric chitosan membrane with AgSD integration is less cytotoxic than the AgSD cream currently in use.

Results and discussion -

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Asymmetric membranes have been reported to be prepared using the dry/wet phase separation method. In the current study, asymmetric chitosan membranes were created using the dry/wet phase separation method using the aqueous acetic solution as a casting solution and aqueous alkaline solution as a nonsolvent (coagulant). In the current study, an asymmetric chitosan membrane combined with AgSD is created as an antibacterial

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wound dressing, and the porosity of the sponge-like porous layer and the thickness of the dense skin can be changed to control the rate of drug release. As evidenced by the smaller inhibition zone, the antimicrobial studies of AgSD-incorporated asymmetric chitosan membrane against Staphylococcus aureus were found to be less effective than those against Pseudomonas aeruginosa. The growth of 3T3 fibroblasts was examined in the cell-culture assay to compare the cytotoxicity of AgSD cream and AgSD-incorporated asymmetric chitosan membrane containing the same quantity of pure AgSD. It appears that the test quantity of the conventionally applied AgSD cream was cytotoxic. The delivery of AgSD effectively and safely might be achieved by using a rate-controlling chitosan membrane.

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A self-healing and injectable oxidized quaternized guar gum/carboxymethyl chitosan hydrogel with efficient hemostatic and antibacterial properties for wound dressing -

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Conclusion -

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effective for long-term bacterial inhibition and less cytotoxic. The findings suggest that the asymmetric chitosan membrane with AgSD incorporation may be a very promising wound dressing with the antibacterial capability to shield injured skin from infections.

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Antimicrobial cream should be applied to the injured area once or twice daily as part of the traditional treatment for severe burn wounds. However, each application frequently results in a significant amount of discomfort for the patients, and intensive nursing care is also needed. In this study, the asymmetric chitosan membrane was prepared and loaded with AgSD, which allowed for the burst-release of sulfadiazine and the slow release of silver into the burn wound beneath to control bacterial growth. It has been demonstrated that the asymmetric chitosan membrane with AgSD integration is both highly

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A quaternization graft reaction followed by oxidation was suggested as a new technique for changing guar gum (GG). Due to the addition of quaternary ammonium groups, the resulting oxidised quaternized guar gum (OQGG) functions as an antibacterial agent. To create a hydrogel with antibacterial, hemostatic, self-repairing, and injectable properties, OQGG was combined with carboxymethyl chitosan (CMCS). Carboxymethyl chitosan (CMCS) not only keeps excellent chitosan qualities like biocompatibility, antibacterial properties, etc. but also adds some new ones like good water solubility. Due to their straightforward preparation, simple availability of raw materials, injectability, and selfhealing qualities, Schiff-base-based hydrogels are highly favoured. Schiff-base-based hydrogels achieve self-healing via imine bond, which lowers the need for frequent dressing replacement and the likelihood of secondary injuries. The raw materials are placed in a syringe and then extruded to apply to the wound, which can reduce the wound surface. The injectability of the

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materials allows them to be applied to irregular wounds. A 22-gauge needle could extract it without stifling. OQGG@CMCS hydrogels were able to be applied to irregular wounds due to their injectability. Unfortunately, Schiff-base-based hydrogels were unable to reduce bacterial infection in wounds. The antibacterial capacity of OQGG@CMCS hydrogels increased with the addition of more OQGG components to form a gel. The antibacterial activity of OQGG was mainly attributed to the presence of positively charged quaternary ammonium salt groups, which interacted with negatively charged protein, lipid, and carbohydrate residues on the surface of bacterial cells, resulting in bacterial inactivation or damage.

Different types of HA-based dressing for wound healing

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When tested on oral and non-oral microorganisms in the planktonic phase, higher MWHA showed better effects in minimising bacterial contamination, according to research on the bacteriostatic properties of HA at different molecular weights (MW), low (L), medium (M), and high (H). - HA demonstrated the strongest bacteriostatic effects on P. aeruginosa, S. aureus, S. epidermidis, and bhemolytic Streptococcus when compared to PLGA, Collagen I, and Hydroxyapatite. - To justify HA's bacteriostatic effect, two theories can be taken into account: 1- First, because HA is a macromolecule, the presence of long chains causes a high-viscosity solution that hinders bacterial motion and diffusion. This is demonstrated by the fact that solutions with high concentrations of HMWHA exhibited strong bacteriostatic activity. 2- A second potential mechanism interacts with the first one in such a way that the saturation of the bacterial hyaluronate lyase may result from an excess of HA. As a result, bacteria appear to lose their

3. Hyaluronic acid Hyaluronic Acid-Based Wound Dressing with Antimicrobial Properties for Wound Healing Application -

In wound dressing applications, HA is frequently used in a variety of morphologies, including films, hydrogels, fibres, non-woven fabrics, and foams.

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ability to penetrate tissue, enabling the host to mount a successful immune response. Improving HA’s inherent antibacterial activity is achieved by: 1- Modification of HA. 2- Combining it with other antimicrobial agents.

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1- Modification of HA: -

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Numerous modification techniques have been suggested in the literature to further enhance HA's innate antibacterial activity. As an illustration, polyurethane films were coated with an earlier version of HA that has thiol groups (HA-SH), using polydopamine as the binding agent. Following this, octadecyl acrylate (C18) was used to bind thiol groups in order to attract albumin. This allowed the system to specifically bind albumin, a protein that is responsible for bacterial adhesion and provided an effective antimicrobial activity. The engineered film's antimicrobial susceptibility was tested against S. aureus by evaluating its adhesion to confirm this assessment. Results showed how the highest amount of adhered bacteria was detected where no C18 was present.

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2- Combination of HA with antimicrobial agents: -

Silver nanoparticles (AgNPs) are among the most commonly used synthetic materials because they can be produced in a variety of ways without the use of potentially toxic materials and are quite simple to obtain. HA4 (H MW HA seeded with AgNPs) showed improved granulation and inflammatory mediators in impaired older and diabetic wound healing when compared to the samples at L MWHA (HA1), M MWHA (HA3), and H MW (HA2) without nanoparticles. Regarding the inhibition of pathogenic bacteria, it was discovered that when compared to the control non-treated rats, both HA4 and HA2 significantly reduced the number of pathogenic bacteria on wounds over the course of the first 24 hours.

Total count of pathogenic bacteria grown on the full-thickness wounded skin from older untreated (control, CN) and treated rats. * Indicated the significance in comparison with the control.

Antimicrobials found in HA are effective against a variety of Grampositive and Gram-negative bacteria. However, antimicrobial agents can be used to enhance such properties.

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HA-Based Devices Combining Synthetic Antimicrobial Agents -

1. Silver nanoparticles (AgNPs)

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A topical spray powder with HA sodium salt 0.2% and AgNPs 2.0%, an EC-certified class III medical device, was found to be safe and effective at healing wounds in vascular ulcer patients during a clinical trial. Results revealed that this spray powder is efficient at reducing wound size due to the presence of HA as well as at

controlling bacterial colonization, as evidenced by a decrease in bacterial load (p 0.025). (Table 1). -

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Thermosensitive and injectable hydrogels based on HA, corn silk extract (CSE) and AgNPs were prepared and their potential use as a wound care material was investigated. Both Gram-positive (B. subtilis, S. aureus) and Gram-negative (P. aeruginosa, E. coli) bacteria were resistant to the antibacterial effects of hydrogels. When compared to the controls, which were made up of just one type of biomaterial, the hydrogels allow for quicker wound closure and repair.

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2. Gentamicin sulphate -

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The use of antibiotics coupled with bio-engineered scaffolds has been widely studied. An example is thin films made up of blended collagen, chitosan and HA fabricated by solvent evaporation after the addition of gentamicin sulphate, a common antibiotic for bacterial infections. The antimicrobial activity of such films was tested against S. aureus (Gram-positive bacteria), E. coli and P. aeruginosa (Gram-negative bacteria) by using the diffusion method. Results showed a better efficiency for the samples in which gentamicin sulphate was released from polymeric matrixes, with inhibition zones of approximately25–30 mm HA-Based Devices Combining Natural Antimicrobial Agents

2. Curcumin -

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1. Antimicrobial peptides (AMP) -

recognized as a potential new class of antimicrobial medications that may be able to combat the issue of antibiotic drug resistance. Even at low concentrations, they exert their activity by permeating the cell membranes of bacteria, causing pores or structural flaws to emerge. A specific AMP called Tet213 combined with substrates of alginate, HA and collagen showed how such substrates’ dressings exhibited antimicrobial activity against E. coli, MRSA and S. aureus, inhibiting or killing bacteria in infected wounds. A solution of three polymers was prepared in deionized water with concentrations being 1.2%, 0.5%, and 0.6% (w/v), respectively, and then Tet213 was added. Thus, samples were lyophilized to obtain the wound dressing. Therefore, those wound dressings granted effective healing, enhancing collagen deposition and improving angiogenesis thanks to the fast release of AMP (Table 1).

Antimicrobial peptides (AMP), which are among the naturally occurring compounds that act as antimicrobial agents, have recently come to be

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Curcumin is a natural phenolic substance extracted from the rhizome of Curcuma longa and is claimed to possess antibacterial properties. Curcumin exhibits photodynamic properties, which have been exploited to enhance its antimicrobial efficacy on infected wounds. The effects in vivo and in vitro of curcumin-modified HA (250 kDa) substrates on antimicrobial and wound healing properties have been studied. Both in the dark and upon exposure to blue light, the bactericidal effectiveness of HA conjugate was assessed.

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They explained the bactericidal effect of curcumin by asserting that it inhibits cellular proteins, FtsZ and sortase A, both involved in bacterial cytokinesis and cell adhesion.

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Another antimicrobial bioadhesive hydrogel for wound dressings with inherent antibacterial properties was fabricated by mixing modified HA and "-polylysine (EPL). Antimicrobial properties were tested through haematoxylin and eosin staining, Masson staining, and α-SMA and CD31 staining. Results showed how such hydrogels were able to kill both Gram-positive and Gram-negative bacteria thanks to their high-density positive charge

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4. Quaternized chitosan (QCS) -

A composite hydrogel made up of HA and quaternized chitosan (QCS) has been fabricated in order to find a

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solution for wound healing in the presence of seawater, containing high quantities of sodium and potentially dangerous bacteria. Hydrogels were produced and dialyzed using the HA-CHO, as conducted in the previous example. The antimicrobial activity of QCS is given both by chitosan and by the addition of quaternary ammonium. Double antimicrobial active groups are created by combining polyatomic amino groups with quaternary amino groups, which have inherent antibacterial action. S. aureus antimicrobial activity was evaluated by counting the microorganisms on hydrogel surfaces. Results showed that the addition of quaternized chitosan enhanced the mechanical properties of the hydrogels, which exhibited excellent antibacterial properties compared to the previous reported antibacterial hydrogels in vitro and in vivo.

Antimicrobial agent combination

Type of HA wound dressing

Tested pathogens

Silver Nanoparticles (AgNPs)

Wound healing ability of different MW of hyaluronan in vivo study Hydrogel HA and metallic silver treatment of chronic wounds healing rate and bacterial load control clinical trials Spray powder Anti-bacterial thermosensitive hydrogels based on corn silk extract, HA and Nano silver improve wound healing with antimicrobial properties Hydrogel Antimicrobial activity of a blend of collagen/chitosan / HA with gentamicin sulphate Film Biofunction of antimicrobial peptide-conjugated alginate / HA/collagen resulting in significant inhibition of bacteria in infected wounds with rapid healing Scaffold Wound healing ability of curcumin conjugated to HA in vitro and in vivo evaluation Scaffold Curcumin-grafted HA-modified pullulan polymers as functional wound dressing material Film Dual crosslinked hyaluronic acid/polylysine hydrogel with self-healing ad antibacterial properties for wound healing polymers in vivo study Hydrogel Antimicrobial hyaluronic acid / quaternized chitosan hydrogels for the promotion of seawater-immersion wound healing Hydrogel

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Antimicrobial peptides (AMPs)

Curcumin

polylysine

Quaternized chitosan

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B.subtilis S.aureus E. coli S.aureus E. coli p.aeruginosa E. coli MRSA S.aureus

MRSA

S.aureus E. coli S.aureus E. coli

S.aureus

Different types of HA-based devices combining both synthetic and natural antimicrobial agents with proven antimicrobial activity. -

Conclusions and Future Perspectives -

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As a key component of the connective tissue ECM in all vertebrates, HA performs critical functions in the healing of wounds by facilitating the formation of a fibrin clot and the generation of interleukins and proinflammatory cytokines. HA, especially greater molecular weight HA, exhibits substantial bacteriostatic activity as it aids in reducing bacterial adherence and biofilm formation. HA intrinsic properties can be enhanced using synthetic and natural antimicrobial agents

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Hydrophilicity, biocompatibility, and easily programmable chemical characteristics have allowed HA to be used to create a variety of compositions and forms for wound dressings. The biological activity of HA-based wound dressings could be improved through the incorporation of other biomolecules such as adhesive proteins (e.g., fibronectin, laminin, and fibrinogen) and/or stem cells for accomplishing an improved.

phenolic groups in the presence of hydrogen peroxide. - The biocompatibility of the hydrogels can be increased by reducing the levels of peroxidase enzyme and hydrogen peroxide. - These hydrogels are excellent candidates for cell delivery applications because they may be cross-linked in place. 4. IV Oxidized and acetylated dextran - Acetylated dextran is a biodegradable derivative of dextran. - This modification leads to the insolubility of dextran in aqueous solutions. In this way, it can be dissolved in organic solvents and mixed with synthetic polymers such as polycaprolactone, polyurethane, and Polylactic glycolic acid. - Acetylated dextran has been incorporated with hydrophobic drugs for tissue engineering and drug delivery applications - Oxidized dextran is a polyaldehyde polymer that can be used to cross-link chitosan and other polymers that contain amine groups. Dextran biodegradation

4. Dextran Dextran, as a biological macromolecule for the development of bioactive wound dressing materials: A review of recent progress and future perspectives -

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Dextran Has Excellent biocompatibility, excellent biodegradability, non-toxicity and proven clinical safety The current review will discuss: 1. Derivatives of dextran. 2. Applications, challenges, and future perspectives of dextranbased wound care material.

Derivatives of dextran: 1. Dextran esters - This dextran derivative can be processed into many formulations, including nanoparticles, hydrogels, sponges, and fibres. It is readily soluble in organic solvents. - They are highly stable against hydrolysis in a wide pH range. - They are also biocompatible and do not impart significant toxicity against skin fibroblasts. - Dextran esters with long aliphatic chain conjugates have been used as tissue adhesive scaffolds. 2. Dextran carbonates - It has been shown that dextran carbonates exhibit a random distribution of functional groups in the polymer backbone. - pH-sensitive dextran azide conjugates can be prepared via a hydrophilic grafting agent. The reactive azide groups can be further functionalized with other polymers or drugs. 3. Dextran carbamates - The resulting dextran carbamate can be successfully cross-linked with horse radish peroxidase and conjugated with

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Dextran readily breaks down when in contact with exudates and has a high rate of biodegradation. It is degraded via dextranase which is present in different body organs such as the colon, the spleen, and the lung. Dextran conjugates with a high degree of substitution may be difficult to degrade, and removing the grafted group may be necessary. Only dextran with a substitution degree lower than 100 can be degraded via dextranase.

Available formulations and fabrication methods for the preparation of dextranbased wound dressings -

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Dextran can be processed via various fabrication methods to develop wound dressing materials. In this framework, different techniques such as electrospinning, centrifugal spinning, solvent casting, 3 dimensional (3D) bioprinting, thermally induced phase separation, and pressurized gyration are available. These technologies have been used to successfully manufacture a variety of formulations, including hydrogels, fibrous patches, membranes, sponges, and wafers.

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1. Hydrogels - Dextran's structure has a variety of functional groups, making it simple to cross-link using both physical and chemical processes. - Various growth factors, small molecule drugs, stem cells, extracellular vesicles, and hormones have been incorporated into the matrix of hydrogels. - Hydrogels have a better chance of clinical translation since they can better mimic the skin tissue ECM and have a higher potential to be modified with advanced drug delivery systems.

and then spun onto a collecting mandrel. Fibers with tunable properties can be produced by altering the fabrication method parameters such as the magnitude of the voltage, the feeding rate of the polymer, polymer concentration, and the turning rate of the mandrel. In the wet spinning method, the polymeric solution is spun into a coagulation bath, resulting in the formation of 3D fibrous structures. The obvious benefit of wet spinning over traditional electrospinning is that it can create wound dressings with a bulk structure, giving them a larger capacity to absorb wound exudate. Pressure gyration technique is a versatile method of nanofibers production in which a polymeric solution is pushed out of a perforated metal vessel using high-pressure forces. In this technique, there is no need for high voltage forces and fibres with tailored size distribution and morphology can be produced.

3. Membranes - These wound dressings are composed of two different layers. - A hydrophobic substance is used to create the outer layer. The inner layer, on the other hand, is a porous hydrophilic scaffold that permits exudate absorption, gas exchange, and cell ingrowth.

2. Fibrous patches - various fabrication methods such as conventional needle-spinneret electrospinning, wet-electrospinning, centrifugation electrospinning, and pressure gyration methods have been utilized for the preparation of fibrous wound dressings. - In the conventional electrospinning method, a polymeric solution is subjected to a high positive voltage

4. Sponges and wafers - Drug loading into sponges and wafers can be performed by adding the drug into the polymeric solution and subsequent freeze drying.

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The creation of tissue-engineered constructions based on dextran has advanced significantly in recent years. Dextran-based wound dressings include hydrogels, nanofibers, and sponges. Since they can more closely resemble the ECM of skin tissue and have a greater possibility for modification with cutting-edge drug delivery methods, dextran-based hydrogels appear to have a better likelihood of practical translation than the other forms.

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5. Konjac glucomannan Konjac glucomannan: A review of the structure, physicochemical properties, and wound dressing applications -

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Various gels obtained by modification of KGM through physical and chemical methods have great application potential in wound excipients. KGM aqueous solution has a high viscosity and gelling properties, which can be used as a carrier for the embedding of small molecules. However, KGM also has high apparent viscosity at lower concentrations, which limits the research and application of KGM in encapsulating wall materials. Therefore, it is necessary to modify KGM to improve its mechanical strength and enhance its functional characteristics.

Different forms of KGM-based composite include: 1. 2. 3. 4. -

Strategies for modification of KGM -

Various chemical modification methods and combinations of KGM have been carried out. The main modifications include substitution, extension chain, and degradation. KGM has functional groups such as hydroxyl and acetyl, which can be polymerized with polymers to obtain target composite materials. Suitable biopolymers include polysaccharides, proteins and other materials such as functional nanoparticles & polyphenols. Compounding KGM with different biopolymers to take advantage of their respective strengths can help construct more stable and effective wound dressings. For example, adding functional nanoparticles can improve the mechanical properties of KGM-based materials, and natural active substances such as polyphenols can give KGM gels antioxidants, antibacterial performance, and pH response performance.

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The common modification methods of KGM are physical crosslinking, deacetylation, carboxymethyl modification, oxidation modification, grafting reaction, and esterification.

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Hydrogels. Xerogel. Microcapsules and microspheres. Films and fibres (nanofibers, blend film). Although more research results have been achieved with KGM in wound dressings in the past few years, challenges remain in the use of these hydrogels as wound dressings for the treatment of infected wounds. Therefore, further research and practice in these areas are needed to ensure the safety and performance of KGM-based dressings

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6. Cellulose Designing cellulosic and Nanocellulosic sensors for interface with a protease sequestrant wound-dressing prototype: Implications of material selection for dressing and protease sensor design -

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Chronic wounds are a major clinical problem. The inflammatory phase of wound healing, which lasts longer than the typical 21-day cycle for acute wounds and may go on indefinitely, is where chronic wounds get stuck. Several factors can contribute to the development of chronic wounds. On a molecular level: it is due to an imbalance in cytokines, chemokines, growth factors, electrolytes, and proteolytic enzymes. Proteolytic enzymes including matrix metalloproteases (MMPs) and serine proteases like neutrophil serine protease (human neutrophil elastase, HNE) In general, acute wounds have normal levels of MMPs and HNE, which facilitates the clearance of cellular debris. However, chronic wounds have elevated levels of MMPs and HNE. They are responsible for the degradation of growth factors and the extracellular matrix (ECM) proteins which are essential for epithelium closure. Thus, they delay the healing process and are also considered biomarkers for chronic wound treatment evaluation.

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‘‘Intelligent’’ dressings -

Defined as materials that respond to specific changes in the wound environment i.e., exudate volume, by altering structure or properties to bring about a useful result i.e., moist woundhealing conditions.

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The phrase was first used to describe a material with self-adjusting water vapour rate of transmission capabilities 25 years ago. Biosensors incorporate two critical components: (i) a biomolecule (such as a peptide) and (ii) a transducer surface (carbohydrate, polyurethane, or polysaccharide). Conjugation of the substrate molecules with the transducer surface forms the apex of activation, which is triggered by a biochemical event giving rise to a detection signal. Point of care (POC) diagnostics is becoming an increasingly significant tool in advanced chronic wound care. In this paper, POC diagnostic biosensors are combined with protease-modulating dressings and applied to the detection of a protease biomarker. The beneficial use of diagnostic or theragnostic POC systems is the ability to predict early outcomes, gauge the healing prognosis of the wound, and improve assessment of the effectiveness of wound care treatment. A diagnostic POC sensor is designed to detect a specific biomarker, whereas a theranostic POC approach assists in guiding treatment. Thus, protease sensors may be considered applicable as diagnostic or theragnostic depending on the clinical treatment goals. Here the focus is on elevated HNE as a chronic wound protease biomarker. Scientists prepared an esterase substrate biosensor by immobilizing a fluorogenic moiety directly onto cellulosic gauze using a click. Immobilization of the fluorophore to the cellulose substrate is designed to prevent the release of the fluorophore into the wound, and a biomolecule that

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is putatively biodegradable is released instead. This type of approach also has the potential as a signal-release design that could be used to monitor the release of a therapeutic molecule into the wound. The biocompatible properties of cellulose are attributable in part to cellulose’s low propensity to absorb proteins making it compliant in biological milieus. The hydrophilic material and surface charge derives from an abundance of hydroxyl functionality present in the nanocellulose structure. As discussed above, the ability to combine measurable protease detection with a dressing motif that neutralizes the effect of proteases is one of the specific goals of wound-healing biomaterial design. This study discusses immobilization of the fluorescent elastase tetrapeptide or tripeptide biomolecule substrate with specificity for the HNE-sensing element onto the cellulosic cotton print cloth (CPC) and three Nano cellulosic materials including cellulose nanocrystals (NCs), nanocellulose composites (NCCs), and Nano cellulosic aerogels (NAs).

Selection of transducer surfaces for protease sensor/ dressing material -

Each material evaluated as a protease sensor transducer surface has structural and biophysical characteristics that influence: 1. Its functional properties 2. Sensor sensitivity 3. Interface compatibility with a dressing. - The sensor is selected to be in a compatible interface with the dressing. Results and discussion 1- Specific surface area (SSA) as a function of loading the peptide substrate and protease sensitivity. - The cellulosic and Nano cellulosic materials were evaluated for SSA and peptide-loading capacity. - SSA and peptide-loading values for the cellulose and nanocellulose materials rank as follows pNC>pNA>pNCC>pCPC. - - As a result, when the sensor is being prepared, increasing the SSA of the materials causes the peptide substrates to be loaded onto the transducer surface in a comparable order. 2- Detection sensitivity of the HNE biosensors: - It is a function of transducer surface properties and peptide recognition sequence, which confer affinity for the protease. - The order of the detection sensitivities was found to be pNC>pNA>pNCC>pCPC. - The cellulose Nano crystalline sensor (pNC) is the most sensitive protease biosensor of those examined here, which is consistent with a higher SSA and also parallels the peptide loading on the material.

These molecular sensor features are examined in the context of dressing/sensor properties like: 1. Specific surface area (SSA) as a function of loading the peptide substrate and protease sensitivity. 2. Sequestration of HNE as it relates to the surface charge of the material. 3. Porosity, pore size and water vapour transmission rate.

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3- Porosity, pore size and water vapour transmission rate: - The principal goal of chronic wound dressing design has been to modulate moisture in the wound bed to create a more optimal environment for healing. - Water vapour transmission rates are a function of: 1. Pore size of the material. 2. Porosity of the material. 3. Polarity of the material (wettability). - - The porosity of nanocellulose aerogel is higher but the pore size is less. Cellulose print fabric, on the other hand, has larger pores but less porosity. - According to this, the moisture absorption of the materials ranks in the following order NA>, CPC>, and NCC. - The range of water uptake of the Nano cellulosic materials was from 250% to 1000%. - The study's materials are thought to have diverse compatibility profiles with various kinds of semi-occlusive dressings. - The porous nature of both the NCC and NA and their relative wettability create a compatible design with semipermeable absorbent dressings like hydrocolloids and films. - On the other hand, the increased swelling capacity of the aerogel (NA) would be compatible with an alginate or gauze dressing. - Effect of the sensor materials on dermal fibroblasts incubated overnight - - The materials' effects on fibroblast development and integrity were not shown to be significantly cytotoxic. - Thus, preliminary assessments demonstrate the compatibility of the sensor materials with proliferative cells

The Nanocellulosic sensors seem useful for detecting chronic wound protease. The level of HNE was also found to depend on the type of chronic wound (diabetic, venous pressure, and arterial ulcers). Accordingly, based on the HNE activities that the sensors of this study detect, and the transducer surfaces evaluated here, the detection sensitivity of pNC detects HNE activity at levels present in most types of chronic wounds as listed. On the other hand, the elastase sensitivities of the Pncc and pNA seem to fall within the range indicated by the same report for elevated HNE levels in arterial ulcers Ability to actively sequester HNE protease From wound-like fluid over a 24-h period. The materials possessed the following order of sequestration activity pNC>pNA>pNCC>pCPC. The percentage of sequestration is correlated with the surface charge values of each material, indicating that a higher negative surface charge causes greater sequestration of protease. Previously it has been shown that protease sequestration dressings with a net negative charge under wound conditions remove positively charged serine proteases as HNE from chronic wound fluid. The Nano cellulosic transducers have a greater surface charge ranging from _12 to _42mV compared to CPC (_11 mV) as determined by the Zeta plateau for each material.

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associated with the initiation of wound healing. Conclusions

7. Gelatin Developing a potential antibacterial long-term degradable electrospun gelatin-based composites mats for wound dressing applications

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Here we have evaluated cellulosic and Nanocellulosic materials as an interface for a multilayered intelligent protease-sequestrant wound dressing for chronic wounds. - The proposed dressing both detect and sequester proteases in a simulated wound-like fluid solution via the use of CPC (control) and Nanocellulosic materials (NCs, NCCs, and NAs). - The Nanocellulosic materials were selected because of their: 1. Structural and biophysical similarities to commercially available dressings. 2. Their favourable permeability, moisture retention, charge properties, and/or sensor functions. 3. Their SSA, peptide loading, detection sensitivity, surface charge for sequestration purposes, and permeability as a function of a biosensor layer. - Therefore, the structures of CPC, NCCs and the nanocellulose aerogel demonstrate promise for a potential wound dressing interface as a biosensor layer that would also function as a protease sequestrant. - - Despite the paucity of clinical trials defining diagnostic and therapeutic parameters for wound protease therapy, protease-modulating dressings have been widely used and commercialized for treating chronic wounds. - More precise diagnostic and treatment criteria are required to advance the clinical use of POC protease diagnostic/dressing approaches.

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Electrospun fibrous wound dressings have become promise in wound healing applications due to: 1. Their degradability. 2. High surface area. 3. High porosity. 4. Capability of optimizing and improving them to provide a suitable environment for the growth of living cells and to prevent the growth of pathogens. Gelatin, as a natural biomaterial has shown promise due to its inherent biodegradability, biocompatibility and water absorbability. Dressings must have enough degradation time to achieve optimal management of physical and biological conditions during the wound healing process. Gelatin membranes' weak water resistance and quick disintegration when in contact with water are their principal drawbacks as wound dressing materials. This has led to the use of crosslinking chemicals like glutaraldehyde to enhance the degradability of gelatin membranes. This study aimed to combine gelatin with glycerol, glucose, and silver nanoparticles (Ag NPs), which together could exhibit optimal physicochemical characteristics as long-term electrospun gelatin based mats for wound dressing applications. The aim of this study was thus to develop and investigate antibacterial long-term electrospun gelatin based composites by one of two methods:

1. Combining the gelatin with two components: glycerol and Ag NPs (GELGLYAg). 2. Combining the gelatin with three components glycerol, glucose and Ag NPs (GELGLY GLU Ag).

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Assessment of the antibacterial activity -

The antibacterial activity of electrospun GLY-GEL-Ag, and GELGLYGLU AgNPs were investigated against two strains of bacteria: Staphylococcus aureus (S. aureus) and Escherichia coli.

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Results and discussion -

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Gelatin membranes' weak water resistance and quick disintegration when in contact with water are their principal drawbacks as wound dressing materials. This has led to the use of crosslinking chemicals like glutaraldehyde to enhance the degradability of gelatin membranes. We speculated that the differences between the antibacterial activity of GEL-GLY-Ag and GEL-GLY-GLUAg mats are due to an interaction between gelatin and glucose molecules. The antibacterial tests revealed that both electrospun GEL-GLYAg and GEL-GLY-GLU-Ag fibrous mats have high antibacterial activity against positive and negative bacteria. The good antibacterial activity of electrospun mats is attributed to the Ag NPs.

8. Dressing with different natural polymers Fabrication and Characterization of Low Methoxyl Pectin/Gelatin/Carboxy methyl Cellulose Absorbent Hydrogel Film for Wound Dressing Applications Introduction -

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Conclusion -

The water uptake-degradation results of electrospun GEL-GLY-Ag and GELGLYGLU-Ag mats were taken up to 10 and 14 days, respectively. The GEL-GLY-Ag mat reached the highest water uptake ratio of about 850 % after 10 days with a degradation ratio 95% while the GELGLYGLUAg mat reached the highest water uptake ratio of about 620%after 14 days with a degradation ratio of 90%. The results confirmed that these electrospun gelatin-based fibrous mats exhibited strong antibacterial capacity against S. aureus and E. coli bacteria making them appropriate as wound dressings.

In this study, we have developed antibacterial long-term electrospun GEL-GLY-Ag and GEL-GLY-GLUAg mats of free bead fibres by combining gelatin, glycerol, glucose, and Ag NPs.

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The fluid handling capacity of hydrogel dressings depends on the type of dressing materials, its inherent physicochemical properties, as well as the design of the dressing. Hydrogels can be formed by dissolving natural polymers, such as chitosan, gelatin, collagen, pectin, and carboxymethyl cellulose (CMC) with water. Gelatin, CMC, as well as pectin, have been used in a number of hydrogel formulations as wound dressings, gelatin is used for hemostasis in bleeding wounds. CMC exhibits a high-water bonding affinity with excellent skin compatibility and can maintain an optimal moist environment in the wound region.

Preparation of Hydrogel Films

2. The film thickness was assessed using a thickness gauge. 3. Tensile Strength of hydrogel film was evaluated using a texture analyzer TX. 4. The fluid uptake ability of hydrogel films was determined using a gravimetric method. 5. The water Retention Capacity of the films. 6. The Water Vapor Transmission Rate. 7. The integrity Value.

1. Hydrogel films were produced by separately preparing 1% w/w each of LMP, gelatin, and CMC in deionized water after which they were mixed, heated to 60+/- 0.5 C and held for 1 h, then cooled to 35+/-0.5 C, At this temperature, 0–40% w/w glycerin and 0.3% w/w glutaraldehyde (Glu) were added to the solution under thorough and continuous mixing to crosslink the gelatin and form a hydrogel. 2. All hydrogels were degassed and subsequently casted by pouring approximately 300 g onto the polycarbonate rectangular templates (17 cm length x 8.5 cm width). 3. The hydrogel film was dried in an oven at 40+/-2 C for 48 h., and an optimized volume of 3% w/w CaCl2 was poured on LMP/gelatin/CMC films in the templates. 4. After 24 h, crosslinked films were taken out, additionally washed with deionized water and then air-dried at room temperature for 24h. After the drying step, translucent LMP/gelatin/CMC films were obtained. 5. Povidone-iodine (PI) was loaded onto the hydrogel film that displayed the best tensile and absorption qualities to test its in vitro antibacterial activity. 6. Povidone-iodine was chosen as a model drug since it is one of the most common aseptic used and can be easily incorporated into hydrogel films.

Mechanical Properties of Hydrogel Films -

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Hydrogel Film Characterizations -

The following characterization of the film were assessed:

1. The morphological Analysis was assessed using scanning electron microscopy

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For wound dressing films to be durable and stress-resistant for their application and handling purposes, they must have a high elongation at break, high tensile strength, and low Young's modulus. So, in this investigation, glycerin was utilized as a plasticizer to make the film more flexible. Results revealed that as glycerin content increases, tensile strength and Young's modulus tend to decrease while film elongation percentage increases. This is mostly due to glycerin's capacity to increase flexibility and reduce intermolecular pressures along polymer chains. From the point of hydrogel film strength, poor mechanical properties associated with a rigid polymer network might lead to a low fluid uptake ability. Importantly, high fluid uptake (%) was obtained when glycerin, acting as a humectant, was added to film formulations. - Hydrogel films that were made with higher cross-linker concentrations showed various water retention capacities. When compared to hydrogel films with only one crosslinker, those with two crosslinkers showed a better ability to retain water.

Testing of Antibiotic-Containing Hydrogel Films’ Ability to Confer an Antimicrobial Property. -

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An agar diffusion method was used to investigate the antibacterial activity of hydrogel sheets containing povidoneiodine. Hydrogel films containing 10% w/w povidone-iodine were placed on prepared bacterial agar plates containing S. Aureus. Test samples were kept in a 37⁰ C Incubator under aerobic cultivation overnight until bacterial lawns were visible. After a 12 hours incubation period, the diameter of an inhibition zone was determined. The produced film's in vitro antibacterial activity against S. aureus suggested that it would be useful as an antibiotic delivery vessel that speeds up wound healing in polymicrobial wound infections. Care must be exercised, though, as iodine-based dressings should not be used on newborns and excessive iodine use can cause hyperthyroidism.

9. Collagen Evaluation of sericin/collagen membranes as prospective wound dressing biomaterial -

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Conclusion -

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Incorporation of povidone-iodine into formulated film conferred its antibacterial property.

- Using numerous cross-linkers, the physical properties of a film formulation made of hydrophilic elements are improved. In this study, LMP/gelatin/CMC hydrogel films were developed. Glycerin was added into film formulations to improve the mechanical properties. The dressing that was created had the best mechanical qualities, fluid absorption capacity, capacity to hold water, rate at which water vapour was transmitted, and integrity value.

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Collagen, one of the most widely used materials for wound dressing, is processed into a variety of products, including films, mats, fibres, and gels for creating implants and engineering tissues. Collagen serves as a template for cellular attachment, migration, and proliferation in addition to promoting the cellular components of healing such as granulocytes and macrophages. Cells such as fibroblasts and keratinocytes specifically recognize collagen substrates. Sericin, constituting 25–30% of silk, envelops the fibroin fibres and provides important attributes such as excellent oxygen permeability, antioxidant action, moisture regulating ability, UV resistance, antibacterial, anticancer and anticoagulant properties. Different areas of sericin use in cosmetics and biomedical applications have been reviewed. A fibroin-mixed-sericin wound dressing that could accelerate healing and be peeled off without disturbing the newly formed skin is designed The attachment of primary cultured human fibroblasts was enhanced with sericin. However, sericin has been implicated as the cause of immune responses to silk when it was used together with fibroin.

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Sericin cream had a wound-healing effect without causing any allergic reactions. This work described the development of the first wound dressing membrane made of collagen and sericin proteins. When these proteins are used together for wound healing, their natural qualities—specialized sericin's roles in the cocoon and collagen's status as a native skin matrix component—bring additional benefits. Oxygen permeability, water holding capacity, degradation, mechanical characteristics, and biocompatibility of membranes produced at various ratios of two proteins were studied.

The final dry weights of membranes (Wf) were then measured to calculate their weight loss. The weight loss was calculated using the following equation: Weight Loss = Wi –Wf - Membranes from each group were cut into2 × 2 cm2 pieces and their dry weights (W d) were measured. - Each sample was placed in a plastic bottle and immersed in de-ionized water at 37°C. - All bottles were capped tightly to prevent any evaporative water loss. - At different time intervals water inside the bottles was removed. - After the removal of excess surface water by gently blotting with a filter paper, the weights of the swollen membranes were measured (Ws). Finally, the equilibrium degree of swelling (EDS) was calculated using the following equation: DS = Ws –Wd - All tests were repeated five times for each membrane type and all measurements. Discussion

Materials 1. Sericin powder of Bombyx mori 2. collagen Gel fix® Lyophilized Type I Collagen pad) 3. Glutaraldehyde (50% GTA) - Preparation of the membranes Sericin and collagen were separately dissolved in 0.5 M acetic acid (0.4% each) by stirring and homogenizing several times. - Sericin and collagen solutions were then mixed with different weight ratios and casted (120 mL) onto glass Petri plates (12.5 cm in diameter) to be dried at room temperature. - The membranes were then cross-linked with 3% (w/v) glutaraldehyde (GTA) solution (20) for 2 h and rinsed with de-ionized water for 30 min. Finally, they were kept in glycine solution (0.2 M) in distilled water for 30 min to block the unreacted GTA residues. - Membrane degradation studies after measuring the initial dry weight of sericin-collagen membranes (Wi) were immersed in distilled water and incubated in the oven at 37°C for 4 weeks.

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Stability tests showed cross-linked membranes remained mostly stable up to7 weeks (average weight loss was about 32% for the 2:1 S/C group). Studies with selected groups showed that as the sericin ratio increased, per cent weight loss also increased GTA cross-linked sericin/gelatin films fabricated by Mandal et al. (25) had blending ratios ranging from 0.5:5 to 7.5:5 (w/w) and the degradation studies carried out on these films showed that with an increase in sericin concentration, higher degradation was observed. Weight loss in membranes was thought to occur with hydrolytic degradation. Hence, the more hydrophilic the proteins are the more hydrolytic degradation is expected to take place.

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Sericin has hydrophilic properties due to the presence of several hydroxyl groups (26). On the contrary, collagen is more hydrophobic due to highly non-polar side groups of its amino acids (27). However, the effect of sericin in increasing the hydrophilicity was observed at an equal or higher proportion of sericin content. A skin scaffold having a biodegradation time for about 25 days could be suggested for healing acute wounds. While a more rapid biodegradation rate would make it inappropriate for healing, a too-slow degradation would prevent the wound healing process. In this study, membranes had high resistance to hydrolytic degradation during 4 weeks of incubation and maintained their structural integrity to a great extent. However, the degradation rate is expected to increase under in vivo conditions. Equilibrium degree of swelling. An important parameter for the evaluation of a wound dressing material is the ability to absorb water. All sericin-containing membranes had higher EDS values than pure collagen ones (0:1). This result was compatible with the previously stated higher hydrophilicity of sericin compared to collagen. Besides that, sericin has an important property; it consists of about 30% serine amino acid, which is related to the moisture absorbing and desorbing capabilities. Thus, with the presence of this amino acid, sericin becomes an excellent moisturizing agent. Therefore, sericin is suitable as a wound-healing material. Yoshii et al. produced a hydrogel blend of sericin, fibroin and PVA. This hydrogel was shown to have excellent

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moisture-absorbing and desorbing properties. The experimental findings indicating sericin-containing groups had higher EDS values than the groups consisting only of collagen were therefore consistent with the inherent features of sericin. Similarly, polyurethane foams containing sericin produced outstanding results for the same attributes. There are studies in the literature to improve the wound dressing properties with the combinational use of polymers. To stabilize the collagen membranes, glutaraldehyde crosslinking is commonly used. However, GTA cross-linking was shown to decrease the water uptake. GTA cross-linked collagen and chitosan films fabricated by the casting method had lower EDS ratios (0.3–0.7, g/g) than the cross-linked sericin/ collagen membranes of the current study (6.22–9.06, g/g) EDS of collagen/chitosan nanofibrous wound dressing membranes prepared was 9 g/g but decreased to 2.7 g/g after cross-linking with GTA.

Oxygen penetration 1. The results of oxygen permeability properties of membranes demonstrated that 2:1 and 1:2 S/C membranes had significantly higher permeability to oxygen than collagen-only membranes 2. Addition of sericin to the membranes could enhance oxygen permeability. 3. Sericin and fibroin films displayed good oxygen permeability, which mirrored the functional characteristics of the human cornea.

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Microbial penetration

In vitro cell culture studies

1. According to the experiment's results, no membrane allowed microbiological penetration for a week. 2. Sericin's antibacterial capability was demonstrated. This trait of sericin will provide it with an added benefit during in vivo applications in the healing process against secondary infections. A prior study found that 64 layers of gauze were insufficient to stop foreign germs from entering the wound. Because of their thick structure and antibacterial qualities, sericin/collagen membranes are therefore thought to have a high potential for wound healing-protection reasons.

1. Initial attachment of keratinocytes to membranes was higher compared to positive controls, as shown by significantly higher OD values for 24 h post-seeding. 2. Compared to the other membranes and the control, cell attachment to collagen membranes was much higher. 3. Adhesion proteins such as collagen, laminin, fibronectin, and vitronectin are present in ECM and contain an arginine–glycine–aspartic (RGD) acid sequence recognized by cell surface receptors, and integrins. 4. The integrins mediate cell-cell and cell–ECM adhesion. 5. It was stated that because integrin binds to the cell adhesion domains in collagen, it is hypothesized that high collagen concentration will encourage cell attachment. Collagen's integrin binding sites were therefore assumed to facilitate keratinocyte adhesion when it was present in membranes. 6. The OD increase observed on all membranes between days 1 and 7 was significant indicating the proliferation of keratinocytes. There was no statistical difference among membranes but the MTT readings on membranes were significantly lower than those for the control on days 4 and 7. 7. When compared to collagen-only membranes, the inclusion of sericin did not significantly affect the proliferation of keratinocytes. 8. Similar to the MTT results of keratinocytes, the initial attachment of fibroblasts on collagen-only membranes was high. 9. The OD increase observed on 1:1 and 2:1 S/C membranes between days 1–4 and 1–7 might indicate the proliferation of fibroblasts.

Mechanical properties -

There was a decreasing trend in the ultimate tensile strength (UTS) of membranes with increasing sericin content. 1. Collagen-only membranes had significantly higher UTS (44.92± 3.72 MPa) than all sericin-containing ones (1:1, 2:1, S/C) except for 1:2. 2. Explanation for the decrease in UTS of membranes upon sericin addition might be the loss of secondary structure (beta-sheets) of sericin protein due to the denaturation of sericin during either extraction from the silk or processing stages of the membrane. Also, there seems to be a relation between the β-sheets formation and gelation. 3. Hence, we inferred that sericin/collagen membranes produced without the gelation step might be the reason for the decrease in UTS in this study.

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10. For all incubation times, the level of proliferation on collagen membranes was considerably higher than in the other groups. 11. It was also observed that the cell proliferation on 1:2, 1:1, and 2:1 was not statistically different from each other for any of the incubation periods. 12. According to Mandal et al analysis of the survival and growth of fibroblasts on sericin/gelatin films, the films with high sericin concentrations showed decreased cellular activity after 4 and 6 days of culture and lower rates of proliferation over the course of one week.

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Conclusion -

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- Various studies have been conducted to evaluate sericin's immunogenicity. Sericin's use in vivo is being promoted by several research evaluating its potential inflammatory response. The results of macrophage response to sericin tests lasting for 1 week period in the research of Mandal et al. (25) suggested that sericin may be assumed not to be very inflammatory in nature. The cytokine levels (TNF-α and IL-1β) were measured for silk sericin cream and control groups (normal saline soak and cream base-treated wounds and it was found that the levels of both inflammatory mediators were lower in sericin-treated wounds than the other control groups. This result suggested that the minor irritability to the cells caused by sericin if any, should be considered an acute rather than chronic inflammation. Sericin when attached to fibroin fibres provides better adhesion to macrophages or primes the macrophages for subsequent stimulation due to its conformational change upon binding to silk fibre.

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This might be comparable to our situation, in which the sericin/collagen membranes allowed macrophages to adhere to the membrane surface, resulting in the development of MNGC. It was reported that adherent macrophages are fused to form MNGC on the biomaterial surfaces as a result of macrophage–biomaterial interaction. A significant increase in the number of MNGC after 2 weeks was observed in sericin-containing groups. This was thought to be due to the resorption process of the material between the second and third weeks, in which the release of the small degradation products near the membrane caused a sharp increase in the number of MNGC. Sericin addition to collagen improved EDS and oxygen permeability properties. - Membranes containing sericin were discovered to be mechanically appropriate for use in wound dressing applications, although there appears to be a trend that the mechanical qualities deteriorate as the sericin ratio rises. Together with in vivo degradation of membranes, it can be suggested that higher proportions of sericin (2:1) might not be suitable wound dressing materials as the other groups (1:1 and 1:2). Sericin/collagen membranes were biocompatible, and they were highly favoured by keratinocytes indicating their prospective efficiency in skin wound-related applications. Presence of sericin in membranes did not cause a significant difference in acute inflammatory and cellular response in rats compared to collagenonly membranes.

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The in vivo reaction to membranes containing sericin was generally mild, and these groups totally disintegrated after three weeks. Sericin addition to collagen can provide membranes that have better properties for wound healing applications like EDS, oxygen permeability and cellular attachment besides its antibacterial and UV protective properties.

In conclusion, traditional wound dressings and treatment methods offer few advantages in wound care and are primarily designed to keep wounds safe from outside influences. Recent advancements have increased the importance and interest of biopolymers for researchers and medical professionals looking for better wound care. Biopolymers are synthetic or natural polymers made by living things. It is said that they are very biocompatible and biodegradable. A variety of health benefits, including antibacterial, antiinflammatory, hemostatic, cell proliferative, and angiogenic activities, are currently documented by studies on biopolymers. These benefits are essential for successful wound management. Chitosan, cellulose, collagen, hyaluronic acid, and alginic acid are a few biopolymers that have already been studied and used as dressings for wounds. Additionally, several biopolymer derivatives have been created by crosslinking with other compounds, In this chapter, current applications of common bio-polymers in the wound treatment industry are highlighted to be a guide for further applications and studies.

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CHAPTER

6 Wafaa Mahmoud Abdellatif , Mustafa Mohamed Elkamah , Ibrahim Ahmed Elsherbini

Synthetic Wound Dressing Material It’s unrealistic to expect a singular dressing to embrace all characteristics that would fulfil a generic need for wound healing Asymmetric polyurethane membrane with an antibacterial activity that responds to inflammation for potential use in wound dressing

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Polyurethane wound dressing -

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Conventional PU dressing appears to still be far from optimum, necessitating re-engineering. Polyurethanes (PUs) have been widely used in many areas such as medical, automotive and chemical industry fields due to their wide range of properties and processing technologies. PU is well-known for its superior strength and favourable biocompatibility

Composition: -

Advantages: -

Good physical strength Abrasion resistance Fatigue life Tissue compatibility

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Disadvantageous: -

Conventional PU dressing lies in the incorporation of antibiotics for prophylactic treatment of an infection which leads to: 1) Irritation and toxicity: - Sulfanilamide can lead to several lethal manifestations of hypersensitivity reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. 2) Resistance as with penicillin and erythromycin

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Low moisture vapour/gas transmission Poor exudate absorption capability The drainage capacity in most cases is not sufficient to prevent the formation of blisters, so dressings have to be replaced or punctured.

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Di amino-containing antibiotic sulfanilamide (SA) as a chain extender to couple iso cyanate terminals of PU prepolymer Using a mix of solvent evaporation and wet phase inversion membraneformation procedures, SA conjugated PU polymer was created into an asymmetric membrane in this study. By using the presence of common infections as a trigger, the dressing may release antibiotics as needed in response to inflammation.

with newborn tissues, allowing for unimpeded wound healing. The porosity of ASPU membranes was found to increase substantially with decreasing solvent evaporation time-as a consequence, a gradual increase in Bet-surface area was observed with shortened solvent evaporation time

Results and discussion: 1-Membrane morphology -

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In order to provide a multi-functional candidate for a prospective wound dressing application, an asymmetric PU membrane was successfully created from a new antibioticconjugated PU employing solvent evaporation and wet phase inversion techniques. A polymer-rich phase and a polymerlean phase were created from the PU solution. The former eventually created the skeleton of the sublayer, and the latter helped to embed pores. This sublayer’s porous design serves as a drainage reservoir. The antibiotic conjugated PU polymer designed as susceptible to repurchase enabled antibiotic delivery on demand from the dressing in response to inflammation ASPU membranes exhibited double layered structure as designed, while details of each component varied as a function of solvent evaporation time These transcendentalist fluctuations in evaporation duration affected the MVTR/gas permeability and drainage capacity of ASPU membranes, which controlled their essential functions as biomedical dressings. It was recommended that the ideal average diameter of pores perforated on the wound contact interface of a dressing should not exceed 15 ml. Such recommendation was proposed by taking into account the size of epithelial fibroblasts, and endothelial cells relevant for human wound and soft cells tissue healing, which had been validated by means of experimental design as well Although ASPU membranes in this study had porous wound contact surfaces, they were less likely to tangle

2-MVTR and gas permeability -

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In the current study, an asymmetric PU membrane dressing was created using a unique membrane-forming technique that combined solvent evaporation and wet phase inversion techniques. The ratelimiting factor for moisture transmission in this membrane was a dense skin layer with variable thickness, which made it easier to manipulate MVTR by varying the solvent evaporation time there. As for oxygen, the permeability coefficients were independent of feed pressure in all In the case of carbon dioxide, however, the permeability coefficients tended to decrease with increasing feed pressure according to the linear regression results The water absorption of Bi occlusive Tegaderm and op site only ranged from 31 to 46 %, and consequently, their applications were limited to non- exuding wounds The ASPU membranes prepared in this study were capable of accommodating water equivalent to 1–3 times their own dry weight due to the presence of a porous undersigned as a drainage reservoir In addition, the equilibrium intercontinental was also found much higher than those of

Bioclusive which were as low as 2136%

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And concluded that SA conjugated PU was not harmful to the normal functions of NHDFs

3-Resistance against bacteria penetration

Optical microscope observation

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The optimum dressing should protect the wound from the elements and prevent viruses, germs, or other pathogenic organisms from entering. To evaluate the superconductivity of E. coli was injected from the skin layer surface but, no contaminants were detected in the outflow This impermeability was further confirmed by observation These results suggested that the thin skin layer of the ASPU membrane was efficient in enclosing the wound beds in case of exposure to external pathogens during the healing process

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Conclusion -

4-Enzymatically switchable SA release -

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If antimicrobial enchantments or antibiotics aren't used promptly, bacteria that survive in sweat glands and hair follicles may still heavily colonize wounds and cause inflammation. Local and intermittent antibiotic treatments based on the varying symptoms are preferable clinically to continuous administration. By urease-catalyzed cleavage of urea linkages, the ASPU dressing would be capable of releasing free SA drugs target pollutants in response to inflammation while reducing the risks of antibiotic toxicity and the emergence of antibiotic resistance.

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5-Cytotoxicity -

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NHDFs not only remained viable but also proliferated in the presence of ASPU7.5, faster than those in negative control for the same seeding time It could be concluded that the SAConjugated PU would not cause any cytotoxicity for NHDFs, thus biomedical dressing made by such conjugate might be bio-compatible

In the event of any secondary injury, qualified wound dressing material is expected to show no cytotoxicity. The morphologies of NHDFs cultured around ASPU7.5 at different time intervals

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The current study showed that it is possible to create a multi-functional PU wound dressing using a new antibiotic-conjugated PU polymer with enzymatic susceptibility by combining solvent evaporation and wet phase inversion procedures. Each component of the ASPU membrane obtained played a respective role when applied on wound beds, synergistically creating a suitable microenvironment for proper healing. 1) The skin layer was capable of preventing bacteria invasion 2) While the sub-layer drained excessive exudates By altering the duration of solvent evaporation, crucial performances of ASPU membrane as biomedical dressing could be tailored to optimize MVTR, allow fast gas microcirculation, and endow highlighter Utilizing bacteria derived urease as a biological signal, the urea linkages in SA conjugated PU backbone could be catalytically cleaved, which enabled inflammation responsive release of SA molecules from the ASPU membrane. The ASPU membrane was noncytotoxic to NHDFs, which promised

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its possible application as a biocompatible dressing material The multi-functional ASPU membrane designed in this study might be clinically suitable as an ideal biomedical dressing for wound care

Membrane Preparation and Characterization 1. Polyurethane membranes were prepared by the casting-evaporation technique 2. The morphological characterization of the PU membranes was carried out by examining the cross-section and surface of the membranes by film properties such as - Drying time, - Alkali and acid resistance, - Flexibility - Adhesion, - Hardness

Polyurethane Films for Wound Dressing Applications -

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PU films have great importance in wound dressing applications since they are: - Elastic - Transparent - Adhesive - Allow a moist environment for the wound - Acts as a barrier to external contamination The dressing developed in this study falls under the category of transparent films

were determined according to the ASTM standards 3. Using a constant volume/variable pressure gas permeability apparatus, the membranes' gas permeability was assessed.

This study aims to produce polyesterbased PU films based on renewable sources instead of petroleum-based polyurethane films. -

Results and Discussion -

PU films are mostly used on dry- or low-exudate wounds

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Polymer Synthesis and Characterization -

Oil-based polyurethanes were synthesized using the solvent method Xylene was used as the solvent. Reaction was carried out at 90- 95°C under an inert gas atmosphere The equivalent amounts of diisocyanate components were added to the polyol

Membrane Code

Ratio of isocyanate components (HMDI: MDI)

PU1 PU2 PU3 PU4

1:0 0.50: 0.50 0: 1 Blend of PU1 and PU3 1: 1

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The molecular weight and polydispersity of the polymer increase with increasing aromatic structure Tg (glass transition temperatures) is strongly influenced by the chemical structure and molecular weight of polymers. Tg increases with decreasing flexibility of the polymer chain. Flexibility decreases with increasing aromatic groups in the main chain. Tg increases with increasing molecular weight at low molecular weights, however, at moderate molecular weights, it reaches to a value at which further increase in molecular weight has no important effect on the Tg. The flexibility of all the PU membranes prepared was superior and the same as the Opposite commercial wound dressing sample.

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The hardness tests of the polymers indicated no particular difference because the number of oscillations made by the polymers was nearly the same. Acid resistance was superior for all samples including the Op-site As the aromatic structure of the polymer was increased, the tensile strength values were also observed to increase from 1.28 to 3.80 lbf.

Applied Test Drying Time (set to touch) Adhesion Flexibility Hardness Alkali resistance

PU1

PU2

PU3

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Opsite

6 min

9 min

7 min

9 min

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2B 2mm 2 Remov able

2B 2mm 2 Removab le

0B 2mm 6 Remo vable

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Acid resistance

No change

No change

0B 2mm 2 Partially removab le No change

No change

Tensile strength (IBF)

1.28

1.73

3.80

No chang e 2.53

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Fabrication and Characterization of an Asymmetric Polyurethane Membrane for Use as a Wound Dressing Asymmetric polyurethane membrane Consists of two layers -

The sub-layer has a macro-porous sponge-like structure to achieve a high absorption capacity for fluids and drainage of the wound by capillary forces. The top layer features interconnected micropores to prevent bacterial penetration and quick dehydration of the wound.

Methods and materials: Preparation of the Wound Dressing by Means of the Twostep Process: After immersion of a suspension of a polymer solution and sodium nitrate particles in an ethanol/water mixture, the polymer precipitates and the salt particles are encapsulated by the precipitated polymer. At a later stage, the membrane is immersed in a water bath. The entrapped salt particles dissolve resulting in the formation of macropores. The size and the density of these pores are determined by the type of polymer, solvent and nonsolvent used, as well as by the conditions applied such as polymer concentration and temperature. A polymer solution without sodium citrate particles was used to prepare the top layer. Therefore this layer

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The permeability and selectivity values obtained for the commercial wound dressing sample, Op-site - The gas permeation measurements of PU2 were not possible due to the cracks present in the membrane - PU4, which is a blend of PU1 and PU3, showed the highest gas permeability, which was closer to the values of the commercial product, compared to the other PU membranes prepared. Therefore, it can be used for wound dressing applications. However, its biodegradability and biocompatibility properties should be determined.

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Preparation of the Wound Dressing by Means of the one-step Process: Polyurethane membranes were prepared either by immersion precipitation or by phase inversion from the vapour phase followed by immersion precipitation using a casting machine. The less toxic NMP was used as a solvent instead of DMAC and water was used as a non-solvent while no sodium citrate particles were applied. PVP is used as an enhancer for pore formation. Regular PEU membrane structures were obtained using a polymer solution containing both PVP and ethanol. However, membranes prepared from a PVP-containing polymer solution without ethanol showed macroscopic irregularities. This might be caused by differences in the rate of precipitation of the two solutions. A membrane with the desired pore structure can be prepared using the

only contains micropores

Fabrication of the wound dressing employing a two-step procedure is rather laborious and difficult to perform; to prepare the sub-layer large amounts of salt particles are needed, the wound dressing is handmade and a continuous process is preferred

one-step casting process using a solution of composition PEU/PVP/ NMP/ethanol = 10/5/60/25 (wt%). Both the addition of PVP to the polymer The residence time, the water concentration and the temperature in the vapour gap strongly affect the pore structure. Using short residence times and/or vapour saturated with water of low temperatures results in membranes with dense top layers. The use of long residence times in the vapour gap and/or vapour saturated with water of high temperatures leads to membranes with too large pores in the top layer and a too low density of macro-pores in the sublayer There are differences in pore morphology and thickness of the top layer The presence of a substantial amount of PVP in the wound dressing contributes considerably to the observed higher drainage capacity as compared to the dressing prepared through the two-step process

Wound dressing mat based on Polyurethane/Polyacrylic acid containing Poloxamer: -

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These characteristics will strongly affect the mechanical properties of the wound dressing. Despite the differences in mechanical properties, both types of wound dressings are sufficiently elastic to be applicable near joints.

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Polyurethanes are widely used in wound dressings because of their good barrier properties and oxygen permeability. PU-based wound dressings are already being used commercially under the trade names Tegaderm™ (3 M) and Op-Site. Tegaderm™ and Op-Site are widely known as materials which both prevent bacterial invasion and minimize water loss from a wound PU, as the hydrophobic polymer, has good mechanical strength but lacks cell affinity, however, most of the hydrophilic polymers have high cell affinities; but they have low mechanical strength The rate of epithelialization was increased and the dermis was wellorganized in the wounds coated with electrospun PU. It is reported that a composite nanofibrous material of PU–dextran loaded with ciprofloxacin HCl exposed the simultaneous antibacterial activity along with good cell growth and proliferation and confirmed the efficiency of tissue regeneration on these bio-composite polymer nanofibrous scaffolds. Pluronics have been used to provide viscosity, maintain oil dispersion and controlled release of growth factors, and serve as carriers for antimicrobial agents in wound management. Additionally, pluronic has been shown to encompass healing characteristics. Their mild inflammatory nature can increase the wound healing process along with fibroblast proliferation.

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By increasing the concentration of POLO, the porosity properties of the produced NFs significantly decrease By increasing the concentration of POLO, the water holding or swelling ratio is enhanced. This result may be related to the hydrophilic nature of POLO which increases the swelling ratio and water absorption, and thus leads to the better diffusion of water molecules in the structure of NFs.

Effect of Molecular Weight on the Gel Fraction and Swelling Properties: -

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Fabrication of Poly(ethylene oxide) Hydro-gels for Wound Dressing -

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The hydro-gel powders that are typically applied to open wounds are draining in order to absorb the exudate from the wound. One disadvantage of such hydro-gel material is that the dry substance can tend to bunch up and form clumps before and during application to the wound site. Clumping can also occur after the introduction of the material to the wound site. In addition, the removal of lumps from the wound site without damaging the new tissue is difficult. PEO shows the merit of its relatively low toxicity. However, pure PEO hydro-gel has low mechanical strength and it is very fragile. Poly (ethylene glycol) di acrylate (PEGDA) is a non-toxic, water-soluble and flexible polymer, which has polymerizable end groups. To evaluate the healing effect of PEO/ PEGDA cross-linked hydrogel for wound dressing, wounds on the backs of mice were covered with PEO/PEGDA hydro-gel films.

The maximum gel fraction and the minimum swelling ratio were reached at a dose rate of 300 kGy with a molecular weight of 400,000. However, when the molecular weight of PEO increased; the dissolution of PEO in distilled water was very poor due to increased viscosity. Therefore, the medium molecular weight of PEO (400,000) was used to make PEO and PEO/PEGDA film for further experiments.

Effect of PEGDA Content on Water Vapor Transmission Rate (WVTR): -

The WVTR of the PEO/PEGDA hydro-gel was close to the ideal value for wound dressing.

Effect of PEGDA Content on Mechanical Properties: -

The tensile strength of PEO/PEGDA hydro-gel increased exponentially with increasing PEGDA content due to the increased cross-link density and reached the maximum value (0.48MPa) with 10% of PEGDA, of which strength was10 times higher than that of the pure PEO (0.044 MPa)

Conclusion -

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Results of in vivo study implied that the test material (PEO/PEGDA) has very favourable wound healing effects; size reduction and epithelizing rate acceleration. In addition, PEO/PEGDA hydro-gel film was able to successfully create amicable environments for wound healing. Studies on histopathology also revealed that PEO/PEGDA hydro-gel film promotes the re-epithelialization and normalization of injured areas.

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These findings were considered to be direct evidence that PEO/PEGDA hydro-gel film facilitated the wound healing

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Waterproof and Breathable Wound Dressing Composited By Expanded Poly tetra fluoro ethylene Backing and Hydro-gel -

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Wound dressings with waterproof, breathable, and bacterial-resistant properties are still rarely realized. Most of the commonly used dressings are not waterproof In this work a newly hydrogel-based dressing is designed with a backing of expanded polytetrafluoroethylene (ePTFE) film. ePTFE is a kind of superhydrophobic material with a porous structure of millions of pores per square centimetre. The pore size ( 99.9%). - While the pure ACC sample lacked selectivity against the gram-positive Staphylococcus aureus, the ACCAg composites demonstrated a growth suppression effect that is close to 0% for all forms of the bacterial strain (Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa). - These carbon-based metallic composites have a lot of potential for producing useful additives for wound dressings. - In the near future, a wound regeneration test will be used to evaluate these composites' in vivo effectiveness. Study 4: PLLA–gelatin composite fibre membranes incorporated with functionalized CeNPs as sustainable wound dressing substitute promoting skin regeneration and scar remodelling. -

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The skin, the biggest organ in the body, serves as a barrier to a variety of microorganisms, including bacteria, viruses, and other contaminants like external pollution. Furthermore, it is essential to the body's immune system.

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Large-area trauma of the skin seriously affects the normal function of the body. Besides, the scars have an impact on appearance. Surgical dressings can protect the wound surface and prevent the inflammation caused by bacterial invasion. Traditional wound dressings’ poor cytocompatibility, poor tissue adherence, limited growth activity, and inflammatory reactions prevent them from effectively promoting wound healing. Synthetic polymers that have received FDA (Food and Drug Administration) approval, such as poly-L-lactic acid (PLLA) and poly-(lactic-co-glycolic acid) (PLGA), have strong biocompatibility and biodegradability. Their degradation products are thought to be lactic acid and glycolic acid. A potential matrix for a wound dressing has been developed using PLLA in conjunction with other natural polymers. The rehabilitation and healing of wounds depend heavily on the water absorption and bacteriostasis of wound dressings. FDA-approved natural polymers like gelatin, collagen, and chitosan have been frequently employed to mix for the manufacture of composite matrices in order to increase the hydrophilicity of PLLA micro and nanofiber membrane matrices. Because of its low cost and utilisation of environmentally friendly methods like electrospinning, the PLLA-gelatin composite membranous matrix may be considered to be of particular interest among the many combinations. These membranes could be prepared by an established solution electrospinning technique.

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Gelatin is the most important natural biopolymer material: 1. The water absorption capacity of gelatin is 5–10 times its weight 2. More importantly, gelatin has high levels of glycine, proline, and hydroxyproline, which are thought to hasten wound healing. - There is growing interest in biomedical applications for nano-metal oxides such as zinc oxide (ZnO), copper oxide (CuO), iron oxide (Fe2O3), and more recently cerium oxide (CeO2) nanoparticles - CeO2 nanoparticles (nanoceria or CeNPs or CNPs) are the critical rare earth metal oxides that have gained considerable attention in biological research due to their anti-oxidant and regenerative properties. - It is well known that CeNPs exhibit antibacterial action against both Grampositive and Gram-negative bacteria, which are responsible for wound inflammation, redness, swelling, warmth, and discomfort (e.g., Staphylococcus, Bacillus tetanus, Fine Goldia magna, etc.). - CeNPs are known for inducing angiogenesis by controlling the oxygen environment in the cells. They may be effective nanomedicines for treating acute inflammatory injury and may be used as possible nano-drug additives in wound healing matrix formulations. - The extracellular matrix (ECM) structure can be accurately imitated by electro-spun fibres because of their resemblance to actual tissues in terms of their architectures and diameter characteristics. - In light of the above, the PLLA–gelatin composite polymer was used to entrap aqueous dispersible organosilane functionalized CeNPs as a potent nanodrug to induce better-wound healing. - Using electrospinning, the functionalized CeNP-incorporated composite polymer solutions were employed to create a new,

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straightforward, effective, and sustainable technology.

Schematic illustration of the mechanism of wound healing via neovascularisation, tissue regeneration and scar remodelling. Conclusion - In this study, we aimed to develop a type of wound dressing substitute that could accelerate wound healing. - Solution electrospinning was used to create fibre membranes with CeNPintegrated PLLA-gelatin composite. - After adding gelatin, the PLLA membranes' ability to absorb water was greatly enhanced. - Endothelial cells may be protected from oxidative stress and death by the coexistence of Ce3+ and Ce4+ in CeNPs embedded in and liberated from the fibre membrane matrix. This redox reaction helps to reduce the excessive production of ROS. - The mechanical properties of the composite membranes were excellent. - Wound healing was significantly accelerated by CeNPs. - A potential candidate material to speed wound healing is PLLA-gelatin composite fibre membranes doped with CeNPs. - After a suitable clinical evaluation, PLLA-gelatin composite membranes with CeNP included can be employed as a sustainable basis for the commercial production of an affordable wound dressing alternative.

Study 5: Polyphosphazene and NonCatechol-Based Antibacterial Injectable Hydrogel for Adhesion of Wet Tissues as a Wound dressing. -

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Due to the rise of resistant bacteria, wounds, especially those caused by recent or severe trauma, frequently come with acute bleeding and infection issues. For acute trauma, such as battle wounds, which are incredibly prone to infection and uncontrollable bleeding, traditional wound dressings like gauze or cotton fabric struggle to meet people's needs for wound treatment. There is an urgent need for advanced dressings for acute trauma. The qualities of an ideal dressing, such as the supply of a moist plateau, isolation of the wound site from microorganisms, and stimulation of wound healing, are met by hydrogelbased wound dressings. Bioadhesive hydrogels have strong adaptability in that they can be in situ formed

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For the purpose of reducing bleeding and expediting wound healing, adhere to and fill irregularly shaped flaws. As the perfect complements or substitutes for sutures for closing organ defects, they attracted a lot of attention. In the event of emergency bleeding, the highly adhesive wound dressings can swiftly attach to wounds and seal the bleeding site. However, bodily fluids (blood and mucus), A thin contamination layer or hydration layer on the substrate prevents the bioadhesive from making intimate contact with the surface, which makes it difficult to achieve satisfying wet adherence. Numerous wet adhesives have been developed by imitating 3,4-dihydroxyL-phenylalanine, a catechol amino acid found in the adhesive protein glue, in order to generate effective wet adherence.

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The catechol groups engage in a variety of interactions, including stacking, hydrogen bonding, hydrophobic contact, stacking with cations, and Michael addition. However, it was discovered that the catechol group is susceptible to temperature, oxidation, and pH, making catechol-based wet adhesives problematic for many real-world uses. Research on non-catechol-based adhesives has advanced in an effort to address these disadvantages. Topics covered include dry-crosslinking mechanism, dynamic covalent binding, hydrogen bonding, topological adhesion, electrostatic contact, and more. Adhesive hydrogels containing adjacent cationic-aromatic sequences were created by Fan et al., who also acquired significant electrostatic adhesion and demonstrated quick and reversible adhesion.

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Increasing the density of hydrogen bonding in hydrogels would further enhance the intrinsic interfacial toughness and cohesion. Hydrogels' incorporation with reversible dynamic bonding is another design principle for strong adherence. The hydrogel's interfacial adhesion and bulk cohesion can both be improved by dynamic chemical bonding in the hydrogel. The dynamic boronic acid ester linkages between the phenylboronic acid groups and the hydroxyl groups were used to create a range of injectable hydrogels with inherent antibacterial properties, moist tissue adherence, and self-healing capabilities (Figure 1). The addition of phenylboronic groups created a polycationic polymer with built-in antibacterial capabilities and caution structures on top of poly (N, N-dimethylethylenediaminephazene) (PD AP). The dynamic boronic ester linkages created by combining the polyvinyl alcohol (PVA) solution and the polymer solution modified with a phenylboronic group can act as the crosslinking locations of the 3D network of the PPBA-PVA hydrogels. The hydrogels may swiftly regenerate after being damaged thanks to the hydrogen bonding, dynamic chemical bonding, stacking, and cationinteraction areas in the PPBA-PVA. The hydrogels can produce longlasting antibacterial characteristics through electrostatic contact because of the high grafting ratio of tertiary amine groups and quaternary ammonium (QA) salt groups. To further examine the therapeutic effects of PPBA-PVA dressing in a full-thickness skin defect model, the outcomes of wound closure, histological investigations, and hemostatic qualities were studied in vivo

Results and Discussion - Hexachlorocyclotriphosphazene (HCCP) was ring-opened polymerized to produce polydichlorophosphazene (PDCP), and then nucleophilic substitution was used to produce completely substituted PDAP. - The three elements that influence how hydrogels recover were used to assess the PPBA-capacity PVA's for quick healing: 1) PVA's plentiful hydrogen bonding interaction in the hydrogels network 2) The healing interface's interaction between the benzene ring and other benzene rings 3) The dynamic development at the healing interface between the PVA's hydroxyl group and the benzene boric acid groups (Figure 3a)

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PPBA-PVA hydrogels effectively cling to the skin as well as other substrate surfaces including plastic, glass, and rubber as well as other tissues or organs like the heart, liver, stomach, spleen, and kidney (Figure 5f). After a skin injury, hemostasis is the initial phase of spontaneous healing. Through the use of hemorrhagic liver rat models, we assessed the hemostatic characteristics of PPBA-PVA in addition to encouraging platelet aggregation to prevent clots at the wound site (Figure 6a). Figure 6b shows the bleeding process in rats treated with PPBA-PVA versus untreated rats. Additionally, the hydrogels' strong adherence can successfully seal the incision and stop bleeding. Figure 6c illustrates how PPBA-PVA hydrogels could firmly cling to the surface of the liver, demonstrating the hydrogels' robust adherence to the tissue interface.

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Both the time to hemostasis and the amount of bleeding was significantly reduced in the PPBA-PVA hydrogels treated groups as compared to the amount of bleeding in the untreated group (213.1 30.4 mgin 5 min). - Hydrogel wound dressings with natural antibacterial qualities can successfully restrict bacterial growth in wounds over the long term in addition to serving as a barrier to protect wound tissues from external bacterial infection, which was another pressing need for emergency wound therapy. - All of the PPBA-PVA groups showed fewer inflammatory cells at the wound site when compared to the Tegaderm films. On the ninth day, the skin tissue in the Tegaderm films was still considerably penetrated by inflammatory cells, but it was significantly less so in the PPBAPVA groups. - Additionally, it was noted that there were considerably more fibroblast cells and that the glands and skin epidermis were regenerating. This phenomenon relates to the migration stage of the healing process, which was sped up by the use of PPBA-PVA hydrogels. On the eleventh day, the skin tissue has only begun to recover and the PPBA40-PVA group's collagen fibre structure is visible. - Furthermore, the hydrogel group's restored skin epidermis is thicker than that of the commercial films. - In conclusion, it is evident that PPBAPVA hydrogel itself promotes wound healing, efficiently lowers inflammation throughout the healing process, and speeds up cell epithelialization. Conclusion - The cation-structure modified polyphosphazene (PPBA) and PVA were used to create a set of dynamic boronic acid ester bonds-based adhesive hydrogels that were inspired by barnacle CPs.

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To confirm the several functions of wound dressing, the inherent antibacterial (4 h antibacterial rate 99.6 0.2%), anti-mechanical damage, and anti-swelling behaviour were examined. The hydrogels cling to tissue surfaces strongly in water through cation- and interactions and hydrogen bonding (adhesion strength of 45 kPa). Moreover, in vivo tests showed that the hydrogels may greatly speed up the rate of wound healing and cut the amount of bleeding by 88%. Novel hydrogels can be used in a variety of ways to treat emergency wounds that require immediate hemostasis and anti-infection.

Pictures Chapter 5, 6, 7

Fig. Classification of the GFs delivery systems according to their matrix structures. Source Adapted from Park et al. Ref: Polymeric and Natural Composites book Md Saquib Hasnain Amit Kumar Nayak Saad Alkahtani

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Fig. Some of the common biopolymers used in drug delivery applications Ref: Polymeric and Natural Composites book Md Saquib Hasnain Amit Kumar Nayak Saad Alkahtani

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Fig. Natural polymer composites induced wound healing Ref: Polymeric and Natural Composites book Md Saquib Hasnain Amit Kumar Nayak Saad Alkahtani

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Fig. Photographs of macroscopic appearance of infected wound treated with rhEGF/PUFs; (A) rhEGF(0)/PUF, (B) rhEGF(2.28)/PUF, (C) rhEGF(4.58)/PUF, (D) rhEGF(8.4)/PUF [194]. Reprinted with the permission by Elsevier B.V. (Copyright © 2015) through Copyright Clearance Center. Ref: Z Hussain, HE Thu, AN Shuid, H Katas… - Current drug …, 2018 - ingentaconnect.com

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https://www.google.com/search?q=fibrous+patches+dressing&tbm=isch&ved=2ahUKEwjSoLe5 k8X6AhVNuKQKHcUtDBwQ2cCegQIABAA&oq=fibrous+patches+dressing&gs_lcp=CgNpbWcQA1AAWOUiYOsqaAJwAH gAgAHGAYgBgASAQQwLjEzmAEAoAEBqgELZ3dzLXdpei1pbWfAAQE&sclient=img&ei=92c7Y5LJNM3wk gXF27DgAQ&bih=600&biw=1366&rlz=1C1FHFK_enEG938EG938#imgrc=qPpwFczZEMwFM

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https://www.google.com/search?q=chitoderm+dressing&rlz=1C1FHFK_enEG938EG938&sourc e=lnms&tbm=isch&sa=X&ved=2ahUKEwie4eyIkcX6AhVO2KQKHcAuDy8Q_AUoAXoECAI QAw&biw=1366&bih=600&dpr=1#imgrc=vu-Ay_yKVauWBM

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https://www.google.com/search?q=hemcon+dressing&rlz=1C1FHFK_enEG938EG938&oq=he mcon+drss&aqs=chrome.1.69i57j0i13i19i512j0i8i13i19i30l4.10048j0j15&sourceid=chrome&ie =UTF-8#imgrc=TLMmW-r2dEH1XM

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https://www.google.com/search?q=celox+dressing&tbm=isch&ved=2ahUKEwjX67ORkcX6Ah VHOewKHTSuAhgQ2cCegQIABAA&oq=celox+dressing&gs_lcp=CgNpbWcQAzIHCAAQgAQQEzIICAAQHhAHE BM6BggAEB4QB1CyEliNHWDfLmgAcAB4AIABlAGIAa8GkgEDMC42mAEAoAEBqgELZ 3dzLXdpei1pbWfAAQE&sclient=img&ei=i2U7Y5f6AsfysAe03IrAAQ&bih=600&biw=1366& rlz=1C1FHFK_enEG938EG938#imgrc=kHwTvn2MnrNh_M

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Figure Spraying autologous bone marrow-derived cultured mesenchymal stem cells in a nonhealing wound. The steps we have outlined, including the need for IRB approval, for obtaining and IND, and for constructing a GMP facility culminate in the experimental therapy shown in this photograph (Panels A–D). We used a modification of a fibrin preparation that has been used for many years to deliver fibrin and control bleeding. In our case, we wanted to deliver to a non-healing wound the mesenchymal stem cells isolated and cultured (in our GMP facility) from the patient’s bone marrow. The fibrin was modified by decreasing the fibrinogen and thrombin concentrations and eliminating the protease inhibitor (Panel C). We placed the cells in the fibrinogen solution of the double-barreled syringe (Panel B), which has a common plunger. Upon pushing the plunger, and with the aid of the gas flow, fibrinogen mixes with thrombin and polymerizes to a stem-cellcontaining fibrin polymer upon exit. Panel D shows the fi ne polymer, gel-like, over the wound.

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Figure Junctional epidermolysis bullosa (EB)/other features. He also had wounds on his ears. A serious management problem in these patients is bleeding, which occurs readily as soon as the wound is touched or dressed. Trauma is important in the development of these wounds. We found petrolatum-impregnated gauze to be a reasonable and cost-effective dressing for most of these types of wounds. Slow-release antiseptics have been used to control bacterial colonization. In order to minimize the use of dressings, all of which stick to the wounds and cause further injury upon removal, we have used polymer fi lm sprays.

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Figure Choosing a wound dressing/fragile skin. The skin in the elderly or in patients on corticosteroids (including inhaled preparations for asthma) is very fragile and tears easily (Panel A). Some clinicians like to use adherent fi lm dressings for these wounds and emphasize that the dressings may remain in place until healing has occurred. We disagree with this approach because removal of the adherent dressing will inevitably remove the fragile surrounding skin and create a new wound. The same argument applies to other delicate conditions, such as blistering from pemphigus vulgaris (Panel B). We prefer the use of fi lm spray dressings, which commonly consist of polymers, and which protect the wound for up to 24 hours. Some of these polymer spray dressings do not sting, and so are preferable. A net-like bandage described earlier could then be used as a secondary dressing.

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CHAPTER

8 Ahmed Mohamed Anany, Mahmoud Bassiouny , Ibrahim Ahmed Elsherbini

Types Of Dressing According To Sensitivity To Stimulus -

1. Multifunctional hydrogel as wound dressing for intelligent wound monitoring:

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Introduction -

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Chronic wounds are more difficult to heal due to bacterial infection, cell ageing, and chronic inflammation, and they may result in serious consequences like amputation and sepsis. Conventional dressings may harm developing skin tissue and raise the possibility of infection. Hydrogel offers a variety of special benefits, including superior biocompatibility, mechanical properties, self-healing, and injectability. To enable in-situ wound detection and on-demand therapy, intelligent wound dressing in integrated flexible sensors has become available. Through the use of several biomarkers, intelligent wound dressings can monitor the condition of wounds in real-time (including pH, temperature and uric acid). Offer the potential for drug delivery and a dressing that precisely matches the shape of the wound. The multifunctional hydrogel created for use as 3D printing ink for dressing wounds.

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It has antibacterial, haemostasis, and adhesion qualities. Additionally, a wound's pH level can be visually monitored in real-time as a potential pathological infection early warning indicator. A fluorescent microscope (DMi8, Leica, Germany) was used to observe the cells. The green (492 nm) and red (545 nm) fluorescence. Each experiment was carried out three times.

Results and discussion Design strategies: -

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Polyacrylamide and chitosan quaternary ammonium salt make up the hydrogel (HACC-PAM). Through a straightforward solvent replacement procedure, the colourimetric reagent (litmus) was loaded into the hydrogel. A wound dressing that accurately replicates the geometric contour of the wound through scanning, computer modelling, and 3D printing. To speed up the healing process, a customised multifunctional hydrogel dressing is carefully applied to the wound. A smartphone can record real-time images of the hydrogel, which can then be converted into RGB signals to calculate the pH value of the wound.

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Through the analysis of wound pH signals gathered from the hydrogel with the aid of deep learning technology, personalised wound management offers the evaluation of wound healing status.

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There are three steps: computer modelling, wound scanning, and specialised manufacturing. Colloids and Surfaces Biointerfaces. With the aid of specialised software, the shape and size of the wound are determined through scanning and vectorized through computer modelling. Based on this digital data, a 3D printer further customises a programmable hydrogel wound dressing. Each vectorized wound has a corresponding customised ID that is unique. Wound recognition effectively prevents bacterial infection and resource waste brought on by wound exposure or overcovering, and also achieves precise wound treatment by precisely positioning the effective components into the wound.

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Multifunctional hydrogel wound dressing: -

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A HACC-PAM hydrogel ink for 3D printing wound dressing was created. Made by polymerizing quaternary ammonium chitosan and acrylamide monomer using a radical process. Using Fourier transform infrared spectroscopy, the chemical structures of HACC, PAM, and HACC-PAM hydrogel were confirmed (FTIR). In the HACC-PAM hydrogel, the presence of hydrogen bonds was thought to be responsible for the

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broadening of the peak of O—H at about 3426 cm 1. The stretching vibration of the C-H bond resulted in an additional peak at 1485 cm 1 of the HACC-PAM hydrogel, proving that HACC was successfully incorporated into PAM hydrogels. The HACC-PAM hydrogel has many excellent properties because HACC is a typical natural cationic polymer (e.g., transparency, flexibility, and adhesion) The multifunctional hydrogel's high transparency made it extremely useful for real-time wound status monitoring. Strong water absorption capacity was shown by the microporous network s4 structure along with an equilibrium swelling rate. After reaching an equilibrium with swelling, the hydrogel also maintained a constant rate of swelling and hardly degraded within 30 days. The multifunctional hydrogel's tensile stress-strain curve showed a good degree of stretchability (152%), which was attributed to electrostatic interactions between the positively charged group of HACC and the amide bond of PAM. Different substances could directly adhere to the multifunctional hydrogel with varying degrees of adhesion strength. It was also discovered that when the hydrogel was attached to the interphalangeal joints, it always maintained conformal contact with the dynamic skin without any retraction or rupture during finger movement. The hydrogel was easily removed from the skin of the human arm after 6 hours of adhesion without leaving behind any residue, irritability, or allergic reaction, successfully preventing secondary

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damage during the dressing removal procedure. In order to guard against potential wound infection, HACC gives the hydrogel dressings built-in antibacterial properties. E. coli (Gram-negative bacteria) and S. aureus (Gram-positive bacteria), two common pathogenic microorganisms in skin wounds, were chosen to test the hydrogel's antibacterial capabilities. After co-culturing with multifunctional hydrogels for 12, 24, and 48 hours, the number of colony-forming units (CFU) of both E. coli and S. aureus significantly decreased when compared to the control group. After co-culturing S. aureus with the hydrogel, almost all the bacteria lost their viability, and no colonies formed, which is consistent with the earlier report that HACC has a stronger antibacterial ability against grampositive bacteria. The mouse liver haemorrhaging model was used to assess the hemostatic capacity of multifunctional hydrogels. After 60 seconds, when compared to the untreated control group, total blood loss in the multifunctional hydrogel group was significantly lower at 3.2 mg, (total blood loss was 53.8 mg). Biocompatibility is another crucial aspect to consider. To test the viability of fibroblast cells (NHDF) exposed to the multifunctional hydrogel, the Cell Counting Kit-8 (CCK-8) assay was used. After 1, 3, and 5 days of co-cultivation with the hydrogel, the cell viability data did not differ significantly from the blank control. Dead cells were marked with PI while living cells with intact membranes

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were stained with Calcein-AM (green) (red). The living cells co-cultured with the hydrogel cannot be distinguished from the control group, and as the culture time grew, the cell density increased significantly. The outcomes validated that multifunctional hydrogels for wound dressings have excellent biocompatibility. During the RGB signal monitoring process, the blue signal of the multifunctional hydrogel increased continuously as pH increased, but the red and green signals didn't change significantly. By fitting the relationship between the response intensity of the blue signal and pH, the colourimetric signal could be standardised.

Personalized wound management: -

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A pH of 4 to 6 is regarded as normal for the wound bed. An infection risk is indicated by a pH value between 6 and 7.5, signalling a warning state. It is confirmed that an infection is present when the pH is between 7.5 and 9. After training with the CNN machine learning algorithm, the system used the pH colourimetric signal collected by the multifunctional hydrogel dressing to intelligently evaluate and predict the wound state (normal, warning, and infection).

In vivo wound healing: -

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In order to assess the effectiveness of intelligent wound monitoring with multifunctional hydrogel as a wound dressing to promote wound healing, a mouse full-thickness wound model infected by S. aureus was chosen.

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The outcomes revealed that on day three, the treated group's wound size was significantly smaller than the control group's wound size. On day 9, the treatment group's wound area, yellow pus exudation, redness, and swelling of new tissues all decreased significantly, whereas the control group's wound area was still up to 37.6%. After receiving treatment, the infected wound was almost completely healed on day 15; the wound healing rate was 97.62%. The control group still had visible red, unhealed wounds with eschar, indicating a slower rate of healing. On days 6, 12, and 15, haematoxylin and eosin (H&E) staining and Masson's trichrome (MTC) staining were used to further analyse the wound bed histologically. The treatment group had tighter connective tissue, less inflammation, and thicker epithelial thickness as determined by H&E staining. On day 15, the epidermis of the wound had nearly fully recovered and measured 78.60 μm in thickness. Masson's trichrome staining revealed that the wound surface's regenerated collagen gradually increased (turned blue) over the course of the prolonged healing period.

2. Physical Double-Network Hydrogel Adhesives with Rapid Shape Adaptability, Fast SelfHealing, Antioxidant and NIR/pH Stimulus-Responsiveness for Multidrug-Resistant Bacterial Infection and Removable Wound Dressing: Introduction -

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Conclusion -

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Due to its superior mechanical properties, self-healing capabilities, and biocompatibility, Multifunctional Hydrogel exhibits a significant advantage in the healing of wounds. It has the benefit of speeding up collagen deposition, epithelial regeneration, and wound healing.

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The processes of bleeding, inflammation, proliferation and reepithelialization all play a role in the healing of skin wounds. The ideal dressing should have properties that aid in several processes of wound healing. Hydrogel bandages can keep the wound moist, cool the wound surface, let oxygen infiltrate, and aid in wound healing. In particular, injectable hydrogels have the ability to in situ encapsulate therapeutic agents, fill any wound shape, and integrate multiple functions like anti-oxidation, haemostasis, and tissue adhesion, which can improve wound healing in multiple healing processes. The choice of a dressing for chronic wounds is made based on the dressing's ability to promote healing, ease of application and removal, need for frequent dressing changes, price, and patient comfort. When exposed to NIR radiation, hydrogels with NIR photothermal effects can effectively melt the hydrogel while also exhibiting good local heating properties.

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They are based on synthetic amphiphilic copolymers: - Poly(N-isopropylacrylamide) - Agarose - Gelatin - Chitosan However, physical gelatin hydrogel is not stable at body temperature, and synthetic amphiphilic copolymers lack biological activity. Additionally, agarose hydrogel has a high melting point, and chitosan can only be dissolved in acidic solutions. Gelatin can aid in the repair of skin tissue and has excellent biocompatibility and degradability. By using a clearly defined quadruple H-bonding crosslinking, ureidopyrimidinone (UPY) is used as a supramolecular self-assembly motif to create physical self-healing hydrogels or elastomers. Adding the UPY motif to gelatin can create a physical gelatin hydrogel that is predicted to hasten skin repair. Physical gelatin hydrogels frequently exhibit strong brittleness, poor tissue adhesion, low strength, and poor stability, which severely restrict their use in the treatment of skin tissue healing brought on by motion. Hydrogels with a double network typically have strong mechanical strength. The physical double-network hydrogels have much better mechanical properties than singlephysical network hydrogels in addition to injectability, quick self-healing, and good biocompatibility. Hydrogel adhesive can seal the wound to accelerate wound closure. The adhesive dressing can avoid secondary damage due to:

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The fragility of soft t issue Localized stress Subsequent removal of nondegradable sutures or staples - Simplify operation procedures, - Shorten recovery times - Improve patient care quality. The catechol group contained compounds that exhibit good tissue adhesion, self-healing, and photothermal capacity after complexing with Fe3+. These compounds also have good biocompatibility and free radical scavenging ability. A synthetic-natural hybrid physical double-network hydrogel adhesive can be made by mixing UPY hydrogen bonding cross-linked gelatin with catechol-Fe3+ coordination crosslinked synthetic flexible polymer: - Including the synthetic polymer's flexible network. - The natural gelatin's capacity for healing. - The antioxidant activity - Sterilization by photothermal means. - On-demand photothermal removal and self-healing.

Conclusion -

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Physical double-network hydrogels for multidrug-resistant bacterial infection, wound closure and wound healing applications with quick shape adaptability, quick self-healing, good tissue adhesion, antioxidant activity, and NIR/pH stimulus responsiveness. The hydrogels were made by simply combining physiological solutions of PEGSD2, FeCl3, and GTU. The gel-sol transition or dissolution of the hydrogel could be facilitated by NIR irradiation and/or acidic solution washing.

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In vivo tests showed that the hydrogels had a high killing ratio for MRSA and provided good haemostasis of skin trauma. Promote the formation of granulation tissue, collagen deposition, inflammation regulation, and vascularization to aid in the fullthickness skin wound healing process. For treating MRSA infections, wound closure, and wound healing, the physical double-network hydrogel adhesives are excellent multifunctional dressings that can be removed as needed.

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The entire system was powered by an external battery. - Benefits: - This dressing is anticipated to offer on-demand infection treatment by releasing antibiotics from the hydrogel by in situ UV irradiation and early infection diagnosis via real-time wound temperature monitoring by the integrated sensor. - The integrated system has high monitoring sensitivity, excellent compatibility, and good flexibility. Conclusion -

3. Smart Flexible ElectronicsIntegrated Wound Dressing for Real-Time Monitoring and OnDemand Treatment of Infected Wounds: Introduction -

Wound dressings with the abilities of real-time monitoring, diagnosis during early stages, and on-demand therapy has attracted considerable attention. Components -

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A double-layer structure with a wound plast shape to achieve conformal contact with the wound site. The power management module, circuit control module, and Bluetooth chip were distributed symmetrically on both sides of the upper layer's flexible electronic layer, which also contained a temperature sensor and four UV LEDs embedded in the middle. Gentamicin was covalently grafted into a polyethylene glycol (PEG)-based hydrogel and released upon UV irradiation at 365 nm in the lower layer's UV-responsive antibacterial hydrogel, which was 3 mm thick.

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A smart flexible wound dressing with integrated electronics that can track the temperature of the wound in real-time to detect infections as they develop and deliver on-demand antibiotic treatment.

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CHAPTER

9 Hala Yasser Gaber, Ahmed Mohamed Anany , Ibrahim Ahmed Elsherbini

Types of Dressing According To Charge Of Polymer 1. Conductive Biomaterials as Bioactive Wound Dressing for Wound Healing and Skin Tissue Engineering:

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Introduction -

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Skin function: - Protection from pathogens - Sensing of the external environment - thermoregulation - Conductivity The term "wound" refers to a defect in the skin. Although the skin is capable of self-healing to regain its structural and functional integrity, wound care is still essential to avoid scarring, prevent infection and desiccation, relieve pain, protect the open site, hasten to heal, and prevent infection. This is especially true for large, open wounds and burns. Wound healing is still a challenging and important topic in both clinical and academic studies at the time.

Advantages -

Types of wounds -

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characteristics of the tissue, its innate capacity for regeneration, the type of wound, and other environmental factors. The therapeutic strategies for wounds are versatile: - Hyperbaric oxygen therapy - Negative-pressure therapy - Vacuum-assisted closure - Ultrasound - Electrotherapy (Endogenous wound-induced electric fields of between 40 and 200 mV/mm are generated and quickly start the healing process once the skin is disturbed) - Electrical stimulation (ES), in particular for chronic wounds, has the ability to speed up the entire healing process through a variety of mechanisms.

Acute incision and excision Chronic wounds Phases of the healing process: - Hemostasis, Inflammation, Proliferation, Remodeling Different strategies for managing wound healing depend on the

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Alleviate oedema around the electrode, Guide keratinocyte migration, Enhance re-epithelialization, Direct dermal angiogenesis, Modulate a variety of genes relevant to wound healing, Generate antibacterial effects High efficacy Processing flexibility Ease in handling and management Exudates-induced metal electrode corrosion, irregular wound shape,

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uneven ES distribution due to a large amount of body fluid, and wound status all reduce the effectiveness of electrotherapy. The fundamental concept behind creating conductive wound dressing is to use materials that are electroactive, primarily carbon nanomaterials, conductive polymers (CPs), or metalbased materials. Toto function effectively, conductive materials must be used in conjunction with other functional materials. - Auto/allograft and Xenograft - Cell-based therapy and engineered skin graft - Topical drug and growth factor delivery Wound dressing is a requirement regardless of the classification of the wounds or the wound care method chosen. Traditional passive wound dressings like gauze, bandage, and cotton wool could hardly fit the open wounds because of the: Lack of an active impact on wound healing Adhere to the skin tissue Resulting in dehydration and a second injury after the replacement Modern wound dressings made of biomaterials, in contrast, aim to - Maintaining a moist environment - Managing exudate, - Protection from pathogens, - Antibacterial capacity, - Antioxidant properties, - Injectability, - Self-healing capacity, - Adhesiveness, - Recent advances in appropriate mechanical properties have shown phenomenal benefits in more challenging circumstances.

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Reviewing and categorising the current processes for producing conductive biomaterial in various forms using 2D and 3D morphologies General Design Principles of Conductive Biomaterials for Wound Healing Issues needed to be carefully evaluated: - selection of matrix material composition - structural morphology - Incorporation of conductive material - First selection of matrix material composition - Naturally derived polymers or synthetic polymers Usually used in conjunction with other elements that influence the fabrication process, such as simple blending in 2D or chemical or physical cross-linking in 3D. Soft matrix is created by dynamic covalent bonds or physical crosslinking. 2D Conductive Biomaterials for wound healing: - Film - Membrane - Micro and Nanofibre Novel 2D inorganic conductive nanomaterials such as black phosphorus (BP) and transition metal carbides and nitrides (MXene) Have gained a lot of attention recently due to their electroactivity and shown great promise in biomedical applications due to their biodegradability, photothermal effect, and antibacterial activities. However, because of their limited stability in ambient conditions or liquid media, their applications are confined. All are suitable for use as a wound dressing as they are tough

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mechanically, resist water, and have good oxygen permeability. 3D Conductive biomaterial: - Sponge - Foam - Hydrogel Absorb a large amount of exudate, maintain a moist environment, and act as carriers for bioactive substances and cells Used as wound dressing and scaffold. 2D biomaterials cannot adapt to deep and chronic wounds, and foams with tough nature could not be applied on delicate skin and dry wounds, while hydrogel with relative soft nature may cause wound dehydration and fail long-term use due to inevitable water evaporation and the constant movement of the wounds.

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2D biomaterials: -

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1) Film advantageous Semipermeable (allowing oxygen and water vapour to pass through, while a large amount of fluids and bacteria are blocked) Flexibility, Lightweight and Poor water uptake capacity make them suitable for delicate skin and thin wounds with little exudate Conducive materials can be incorporated into thin films as matrices for bioactive substances, and conductive films have been extensively used to study the mechanism of how conductive materials work. Modulate cell activities. The primary reasons for the use of polypyrrole (PPy), poly(3,4ethylenedioxythiophene (PEDOT), and poly(aniline) and its oligomers are their biocompatibility, ease of synthesis, and tunable conductivity produced by different dopants.

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2) Membrane Is a semipermeable biomaterial that is comparable to a thin film but has a higher capacity to absorb water. As a result, it can be used on wounds with moderate exudate, including superficial wounds, frictional wounds, scratching wounds, and skin donor sites. In terms of quick wound closure, complete reepithelialization of the wound, improved vascularization, and collagen deposition, both conductive and non-conductive membranes significantly outperformed sterile cotton gauze in the healing of wounds. 3) Micro-and Nanofibers Have great potential in tissue engineering for their fibrillar architectural resemblance to ECM. The porous design and large specific surface area allow for oxygen permeation, nutrient exchange, and the absorbency-based management of relatively large exudate. Semi permeable (restrain the penetration of pathogen) Soft and compliant (retain conformity under human movement)

3D conductive biomaterials for wound healing 1) Hydrogel - It is compatible with human skin and has a porous, three-dimensional network of interconnected pores that allows oxygen and water vapour to pass through while maintaining a humid environment, lowering wound temperature, and relieving pain. - Excellent enhanced wound healing was achieved by the ideal hydrogel dressing at all stages, including in vivo blood clotting capacity, promoted ECM synthesis, collagen deposition,

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granulation tissue thickness, and promoted remoulding phase. - Conductive hydrogel is another good choice, in terms of conductivity softness, stretchability, and flexibility. - In terms of conductivity, softness, stretchability, and flexibility, the conductive hydrogel is another excellent option. - Given its antibacterial capacity and reduction of secondary damage during removal, a conductive hydrogel containing poly (2-hydroxyethyl methacrylate and PPy has been shown to be advantageous to commercial hydrogel dressings. - Hydrogel biomaterial's tremendous potential for tissue engineering by serving as a scaffold to support cells and biomolecules is another appealing aspect of it. - Overall, conductive hydrogels have the potential to accelerate the healing of wounds using a variety of methods, making them promising candidates for wound healing, especially for complicated chronic wounds. - On the contrary side, conductive hydrogels have great potential for use in medical devices for wound diagnosis due to their excellent conductivity, simple fabrication process, and easy surface modification. However, the hydrogel's long-term durability might prevent further advancement. 2) Fibrous scaffold - Their applications still constrained by several factors, such as pore size - Cellular infiltration and tissue ingrowth into the scaffold are all impacted by the interconnectivity of the pores. - Small pore sizes did not prevent the use of nanofibers as a wound dressing, but cell attachment and proliferation

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may be constrained on the surface of nanofibers. The requirements of porous scaffolds for tissue engineering applications cannot be met by nanofibers with too compact a structure.

3) Sponge, foam and a cellular dermal matrix - Aerogel and cryo gel derived from hydrogels have sponge-like structures and high water polarity for absorption, which enable them to not only handle a large amount of water but also allow water to flow out and in freely. Pure foam exhibits hydrophobicity when placed on a hydrophilic surface without any additional modifications, benefiting from its innate antibacterial properties. - Foam typically exhibited more enhanced mechanical properties than sponge, which is the slight distinction that differentiates the two. - Practically speaking, burn, ulcer, skin donor area, and transplant wounds can all be treated with foam and sponge dressings. Additionally, they are flexible, lightweight, and simple to use in actual use. - Tissue engineering Colloids and Surfaces have made extensive use of cellular dermal matrix (ADM) derived from human or animal tissue. Bio interfaces, grafts, wound dressing and healing as tissue replacement - The extracellular matrix protein and collagen-based ADM exhibits excellent biocompatibility, suitable mechanical properties, and bioactivity, making it the perfect material for skin tissue scaffolds. - The conductive foam was able to prevent infection and manage necrosis by virtue of its inherent antibacterial activity, good water absorption

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capacity, and electrical conductivity. It could also apply an annular-oriented electrical field to wounds with the help of exogenous electrical fields. To demonstrate the great value of 3D conductive biomaterials in wound dressing as well as their use in electrotherapy, wounds showed the best wound healing effect when the conductive foam was applied with exogenous electrical fields. Additionally, this conductive foam's inherent property of being highly porous allowed it to connect with a negative-pressure drainage closure device and thereby accelerate the healing of wounds.

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Infection Aging

No matter the type of wound, the heali ng process follows a similar, systemati c pattern that includes four distinct pha ses. Hemostasis should ideally start right away after injury and finish in a matter of seconds or hours, depending on the wound’s size, depth, and location. Inflammation then starts, lasts for a few days, and reaches its peak within 72 hours. Proliferation, the third stage, is more challenging. The simultaneous occurrence of angiogenesis, fibroblast migration, granulation tissue formation, collagen deposition, epithelialization, and wound contraction. The final remodelling stage, which allows granulation tissue to transform into mature connective tissue, can last anywhere from a few months to several years. Factors affecting wound healing: - Nutrition - Oxygen supply

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The term "chronic wound" refers to a wound that takes longer than three months to heal. Apparently, chronic wounds need specific treatment including tissue debridement, infection clearance, moisture balance, mechanical support, and management of comorbidities according to the aetiology and realtime diagnosis. Conductive biomaterials demonstrate promising potential in wound healing as well, because they could regulate and promote cell attachment and relevant activities with or without ES that have been convinced by in vitro and in vivo assays To meet the requirements in practice, conductive biomaterials are typically combined with other bioactive substances.

Acute wound -

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An unintentional injury to the skin known as an acute wound can be brought on by surgical incisions, bites, deep lacerations, abrasions, and burns. Acute wounds can spontaneously heal in an orderly routine even without any external intervention

2D biomaterial for acute wound: -

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In acute full-thickness wounds, conductive film membranes and nanofibers have both been found utilised. The electroactivity, antimicrobial activity, and antioxidant capacity of these wound membranes could encourage the growth and proliferation of fibroblasts.

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2D conductive biomaterials always need to be endowed with multiple bioactive functions while fulfilling basic requirements However, some factors, such as the limited ability to manage exudateloading bioactive agents and maintain their biological activities, further functionalization, and low adhesion to the skin, still limit the application of 2D conductive biomaterials in acute wound healing.

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Conductive biomaterials enhance wound healing by several pathways

3D biomaterial for acute wound: -

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In the field of skin tissue and wound dressing, 3D biomaterials such as hydrogels, foams, and sponges have gained a lot more attention due to their great potential for assembling EC4Mlike structures. All conductive materials have been incorporated into different types of 3D biomaterials and have demonstrated their benefits in the treatment of acute full-thickness wounds. 3D biomaterials with highly interconnected porous structures exhibit a number of advantages over 2D biomaterials. 3D biomaterials are suitable for wounds with significant exudate due to their higher water absorption capacity, which prevents frequent removal. The hydrogel-based wound dressing is appropriate for irregular and deep wounds due to its injectability and capacity for self-healing in an ambient environment.

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In the inflammatory phase, exert beneficial effects attributable to their innate antibacterial activities and, if necessary, photothermal antibacterial properties, causing the transition to the proliferation phase. Proved to exhibit antioxidant activity and enhance cell attachment, migration, and proliferation, which benefits both the inflammatory, proliferation and remodelling phases Conductive wound dressing can enhance cell migration, alignment, proliferation, and differentiation with precise programmed electrical stimulation when used as electrodes in electrical therapy. Ideally, at least, take into account combining conductive biomaterial with other particular bioactive agents in chronic wounds.

Infected wound -

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Chronic wounds including diabetic wounds and ulcers could hardly proceed beyond the inflammatory phase. Wound management requires both the disinfection of infected wounds and the protection of wounds from bacterial invasion throughout the healing process.

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Chronic wound, including arterial, diabetic, pressure, and venous ulcers, is a serious threat to human health, and it takes decades to heal and accompanies by severe complication, amputations and even death

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Microorganisms can invade wounds and induce inflammation. Epithelization, and prolonged wound healing process, and eventually lead to chronic bacterial-infected wounds Correspondingly, antibiotics' poor antibacterial effectiveness is caused by their inability to penetrate biofilms. Fortunately, conductive materials that exhibit intrinsic antibacterial and

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photothermal antibacterial activities, such as CPs, carbon Nanomaterials, metals and metal oxides, MXene, and BP, are all excellent substitutes for antibiotics because they are less likely to promote bacterial resistance. Chitosan and its derivatives have frequently been chosen among varying matrix materials for their synergistic innate antibacterial effect. Conductive materials with nanostructure morphology owning increased membrane permeability and multiple antibacterial actions, are other preferential choices to deal with infected wounds Other preferred options for treating infected wounds include conductive materials with nanostructure morphology that have higher membrane permeability and multiple antibacterial effects.

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Wound monitoring -

Diabetic wound -

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absolutely necessary since adequate oxygen supply is crucial for diabetic wound healing. Although electrotherapy has benefits for treating chronic wounds, it is still constrained by the small electrode surface area and inconsistent wound distribution. Overall, conductive biomaterials have demonstrated excellent performance in managing diabetic wounds through different pathways.

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Diabetic wounds exhibited prolonged infection, abnormal angiogenesis, and delayed re-epithelization Preventing bacterial infection, controlling wound infection, inducing angiogenesis, enhancing collagen deposition, and encouraging cell proliferation are the general design principles for wound dressings and scaffolds for diabetic wounds. Conducive biomaterials have excellent healing effects on open wounds and wounds that are infected, nevertheless, they are rarely used solely to treat diabetic wounds. Notably, conductive biomaterials encapsulated with insulin and fibroblast, or with mesenchymal stem cells have demonstrated enhanced diabetic wound healing performance. Delivering oxygen to wound sites in a sustained and controlled manner is

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Several wound dressings with stimuliresponsiveness have been developed that can actively sense the variations and then self-adapt to the wounds. Wound healing is a dynamic process with four overlapped stages, in which many parameters such as humidity, temperature, pH, and glucose levels will change. The first approach uses two unique functional groups to give wound dressings conductivity and stimuli responsiveness. The second approach utilizes a single substance to produce both conductivity and stimuli-responsiveness. Physical examination, wound location, size, depth, and drainage should all be carefully recorded, and subsequent treatment must be adjusted based on the degree of healing. Long-term monitoring, however, requires frequent screenings and hospitalisation of patients. Although some electrochemical sensors were created for wound diagnosis, the wound dressing and wound treatment could not be finalised at the same time. Modern wound care greatly benefits from conductive wound dressings that can detect changes in the wound and then translate those changes into

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electrical signals to enable synchronous wound care and wound monitoring. When compared to healthy skin, which has an acidic pH between 5.5 and 6.5, chronic wounds have an alkaline pH between 7 and 9, or they can have an extremely acidic pH due to severe infection. To track the progress of the chronic wound healing process, the pH level can be continuously measured. Monitoring the levels of several parameters, such as physiological signals, PH, oxygen temperature moisture glucose and uric acid, has facilitated real-time tracking of wound healing.

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Summary and perspectives -

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CPs are limited by poor processability, mechanical brittleness and nonbiodegradability, and the conductive oligomers benefit manufacturing process and good biodegradability, but their conductivity under physiological conditions restricts further practical applications. Metals, metal oxides, and carbon nanomaterials all tend to aggregate in solutions, so additional polymers or methods are always needed to achieve homogeneous dispersion. The cytotoxicity of carbon Nanomaterials and metals and metal oxides also matters in their applications, especially in some research that they are modified with CPs.

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Conductive biomaterials realize their applications in promoting wound healing via three strategies: -

The conductivity of these materials depends on many factors:

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this area, must still overcome a wide range of obstacles. To meet the needs of various types of wounds, conductive biomaterials can be manufactured in a variety of forms. While 3D hydrogels and scaffolds with ECM-like structures are frequently used in more complicated wounds and skin substitutes, 2D biomaterials such as films, micro- and Nanofibers, and membranes can treat acute wounds with fewer exudates. Hydrogel membranes and conductive thin films can also serve as bioelectronics substrates because of their softness, flexibility, and suitable mechanical properties. The ability of conductive film and micro-/nanofibers to absorb water is typically much more limited, and the conductivity is always measured in the dry state. They are thus appropriate for wounds with minimal exudate. Conductive hydrogels fit for wounds with moderate exudates, while 3D porous scaffolds can manage significant exudates. Additionally, conductive fibres, hydrogel, and 43D porous scaffolds are highly competitive in the multifunctional platform due to their ability to be loaded with cells, drugs, and growth factors.

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- PH value - Dopants - Adjacent environment Before completing applications in wound healing, BPs and MXene, which have excellent opportunities in

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They can be applied as compliant electrodes for electrotherapy They exhibit conductivity that is comparable to that of human skin, can be used alone as dressings for wounds or as tissue engineering scaffolds, and support cellular activities to hasten wound healing.

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Stretchable and flexible electronics could be created using conductive biomaterials to provide real-time wound status monitoring. To improve the effectiveness of wound healing using a variety of techniques, bioactive agents, such as medications, proteins, and growth factors, have frequently been incorporated into conductive biomaterials. Incorporating fibronectin, a celladhesive glycoprotein, into PPy/PLLA film improved the fibroblasts' ability to adhere to and move through the conductive film, whereas adding BSA decreased cell adhesion. Because the low concentration and excessive degradation of growth factor on the wound site would slow the healing process, the wound-specific delivery of growth factor is extremely valuable in promoting wound healing efficiency. The maintenance of human activities, including the process of healing wounds, depends greatly on metal ions. Through a doping mechanism, copper and zinc ions were added to the PEDOT-cellulose polymer composite without affecting the substrate's topography and controlled release was achieved. Human keratinocytes directional migration under electric fields requires several growth factors, particularly the epidermal growth factor There have not been many articles on the use of growth factor-loaded conductive biomaterials in skin tissue engineering or wound healing. Furthermore, the uses of conductive biomaterials are still in their early stages and confined to diabetic and infected acute wounds.

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To summarise, the most common method for fabricating conductive biomaterials is to incorporate small amounts of conductivity; the choice of matrix polymers and crosslinking techniques heavily influence the properties of conductive biomaterials. Conducive biomaterials in combination with other bioactive agents and cells are an effective strategy that merits further investigation for accelerating the wound healing process in multiple channels.

2. Suprasorb® X +PHMB: antimicrobial and HydroBalance action in a new wound dressing: Introduction -

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A new antiseptic dressing called Suprasorb X + PHMB lowers the microbial load and promotes healing. Suprasorb X, a unique Hydro Balance dressing that absorbs and donates moisture, with PHMB, an antiseptic compound make it non-cytotoxic Antibiotics are under criticism due to concern over the prevalence of resistant bacteria like Methicillinresistant Staphylococcus aureus (MRSA). Guidelines for MRSA management include avoiding unnecessary use of antibiotics This led to an interest in antiseptics because they are easy to use, available, cost less than antibiotics, and don’t need a prescription. However, there is also evidence for bacterial resistance to some antiseptics, such as silver and no evidence for its cytotoxicity.

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Bacterial contamination expands to all wounds (its presence without growth or host response) The consequences of an increase in bacterial density in wound tissue are described by the Wound Infection Continuum. Additionally, it can be used to track the progress of a wound's recovery. There are four distinct stages: colonised, critically colonised, locally infected, and spreading infected. In colonized wounds, there is no requirement for topical antimicrobial intervention to lessen the wound's bioburden as long as the host exhibits no clinical response. Critically colonized wounds require a reduction in the level of bacteria through antimicrobial involvement after eliminating indolence causes, also antibiotics are unnecessary Localized infection displays the traditional symptoms of inflammation, including hotness, redness, and pain. Antimicrobials are used to treat local infections if there is no risk of the infection spreading. To use topical antiseptic, you need to consider the agent’s ability to reduce micro-organisms, its specificity, cytotoxicity, its potential to select resistant strains and its allergenicity. The dressing's capacity to manage exudate and necrotic tissue, which promote bacterial growth, is another factor to take into account.

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PHMB in wound management -

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PHMB is used in contact lens cleaning solutions, perioperative cleansing solutions and swimming pool cleaners. Exerts little toxicity, no evidence of resistance, and can also kill a diverse range of bacteria and fungi PHMB was successfully used in wound dressings, including nonadherent products, gauze, drains and intravenous sponges. PHMB has been incorporated into a new wound management product, Suprasorb® X +PHMB.

The Suprasorb X dressing range -

Antiseptic agents -

Antiseptics, in contrast to antibiotics, also have numerous target sites, including the membrane and cell wall of bacteria. Silver, iodine, honey, and Polyhexamethylene biguanide are among the topical antiseptics frequently used in wound dressings (PHMB) Synthetic compound structurally similar to antimicrobial peptides (AMPs) and thus exhibits similar functions AMPs are molecules that bind to bacterial cell membranes and induce cell lysis like penicillin. Keratinocytes and neutrophils within the wound produce AMPs, which serve as an anti-infection defence. PHMB make bacterial pumps unable to remove the antiseptics

Antiseptic resistance is less than that of antibiotics Antiseptics differ from antibiotics in that they are generally active against a broader spectrum of organisms

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Composed of biosynthetic Hydro Balance fibres that are byproducts of cellulose fermentation. This results in the dressing having a high surface area, strength, and moisture-handling capacity. Depending on the status of the wound, surplus exudate can be absorbed by the

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dressing, or donated in the case of lightly exuding wounds thus it can be used in high, moderate, non-exuding and dry wounds. Besides this, it shields the wound from external contamination, dehydration, and abrasion. Suprasorb X was found in a study to noticeably enhance the rate of wound closure, significantly promote autolytic debridement, and markedly reduce wound pain. The new dressing, Suprasorb X +PHMB, combines the proven efficacy of Suprasorb X with the antimicrobial action of PHMB. The presence of fluid in the dressing means that antimicrobial activity is possible even on dry wounds

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Suprasorb X + PHMB in clinical practice -

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Clinical studies revealed that PHMB significantly decreased wound bioburden and supported healing. Twelve patients with a total of 26 wounds were evaluated, 11 of whom had previously been unresponsive to silver or iodine-containing dressings Eight patients had organisms found in their wounds prior to treatment, most frequently Pseudomonas aeruginosa and Staphylococcus At the end of the evaluation, levels of bacteria were decreased in five of the eight patients (two patients did not follow up) During the course of the study, two wounds healed and 13 showed improvement. According to a different study, more than 80% of patients treated with Suprasorb X and PHMB experienced healing or clinical improvement.

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83-year-old woman with a history of chronic renal disease, hypertension and venous leg ulceration. The wound was sloughy and painful with high exudate levels i.e., critical colonization. A swab was taken on day 1 and another was taken on day 7 to determine whether the wound bed bacterial load had decreased. The wound was about 13 cm2 in size, and the wound bed was made up of 90% necrotic tissue and 10% granulation tissue with mixed skin flora. Over the Suprasorb X+PHMB, a second foam dressing was applied and held in place with a stockinet and wool bandage. Under the bandaging and foam, the dressing maintained its moisture, and the wound bed improved along with an increase in granulation tissue. Eventually, the overall size of the wound had downsized to 9.4 cm2, and the skin flora had diminished.

Conclusion -

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The ideal antiseptic dressing provides hydration while lowering wound bioburden. To reduce the cytotoxic effects and the selection of resistant bacterial strains, such a dressing must be applied with caution. Suprasorb X + PHMB is able to reduce pathogens in the wound. Currently, PHMB have no history of resistance or cytotoxicity, making it a good alternative to antiseptics that have such a history. The unique moisture-absorbing and/or donating properties of Suprasorb X promote wound healing and pain relief.

Pictures Chapter 9

Schematic representation of wound healing stages. Ref: Biopolymer and Synthetic Polymer-Based Nanocomposites in Wound Dressing Applications: A Review Ravichandran Gobi 1 , Palanisamy Ravichandiran 2,3,4 , Ravi Shanker Babu 1,* and Dong Jin Yoo 2,3,4,*

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(A) Images of the skin wound dressing compared in three groups: hydrogel precursor, preformed hydrogel, and moldable hydrogel groups. (B) Images of the dissolution of O 2 D/T 2 P hydrogel after treatment with an aqueous GSH solution (0.1 M, pH 7.4) for 15 min. Toluidine blue dye was added for visualization. (C, D) Images of scalded wounds (C) at 2 and 18 days and wound size reduction (D) of the hydrogel dressed and saline groups. Data are expressed as the mean ± SD **p < 0.01 (n = 4). (E) H&E staining images of the repair of scalded wounds of the hydrogel dressed group and saline-soaked gauze dressed group at 18 d. P: papillary; black bar = 1 mm; white bar = 200 μm (n = 4). https://www.researchgate.net/figure/A-Images-of-the-skin-wound-dressing-compared-in-threegroups-hydrogel-precursor_fig4_333692638

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Schematic illustration of the PolySBMA/QCSMA/GelMA (SQG) hydrogel (A) with strong chemical bonding and dynamical physical interactions (B) for wound repair (C). PolySBMA, poly(sulfobetaine methacrylate); QCSMA, quaternized chitosan methacrylate; GelMA, gelatin methacrylate. https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC8735859&blobtype=pdf

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Figure Use of a bi-layered bioengineered skin construct. Although this procedure has been shown in other sections as well, we feel it is important to emphasize its importance and sequence. This type of bi-layered skin construct has been available for the treatment of venous ulcers for several years. In fact, it is approved by the FDA for both venous and diabetic ulcers. It is composed of living keratinocytes and fibroblasts derived from human neonatal foreskin. The keratinocyte sheet is grown over a type I bovine collagen gel that contains the fibroblasts. This product is delivered fresh and living in a transwell that contains special nutrients to keep the cells viable. Here, one sees the removal of the construct from the insert using a cotton-tipped applicator (Panel A). The construct is about to be passed through a skin graft mesher before being applied to a venous ulcer (Panels A and B). Skin graft meshers (Panel C) have corresponding carriers that provide varied ratios of meshing. Panel D shows the construct meshed at a ratio of 1.5 to 1. Here it is still on the carrier used to pass it through the mesher. Alternatively, instead of meshing, slits or fenestrations can be made in the construct by using a scalpel, which will still allow the wound exudate to escape and not interfere with the adherence of the construct to the wound bed. The clear advantage of meshing is that the construct (7.5 cm in diameter) will expand and be able to cover a larger wound.

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Figure Treatment with a living dermal construct. In this photograph the neuropathic ulcer on the big toes of this patient with diabetes is being treated with a dermal substitute consisting of living human neonatal dermal fibroblasts in an absorbable matrix material. Besides the living bioengineered skin constructs, we show, there will be other types in the next few years. Some of these constructs will be modifications of the existing ones, (i.e., adding endothelial cells, re-engineering with certain growth factors or matrix gene constructs that are constitutively expressed or whose expression can be regulated by the wound environment). We have also developed the idea that a “priming” step is required, whereby the construct is activated and allowed to develop its full program (increased gene expression for proliferation, migration, and chemotaxis) in vitro before being placed in the hostile ulcer microenvironment.

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Figure Living bi-layered bioengineered skin construct to stimulate healing. This photograph shows the construct in place. In this case, it was not meshed, but small slits (0.5–1.0 cm in length; fenestration) were made in it with a scalpel before application to allow the escape of wound fluid and prevent uplifting and rapid loss of the construct.

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Figure Bioengineered skin treatment and sequence of healing. This series of photographs illustrates the treatment of a venous ulcer with a bi-layered bioengineered skin construct (Panels A through F). The ulcer was debrided (Panel A), treated with the meshed construct (Panel B), and dressed with a petrolatum- and bismuth-impregnated gauze (Panel C). This treatment resulted in complete closure after 2 months (Panels D and E) and remained healed after 4 months (Panel F).

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Figure A diabetic foot ulcer treated with a bi-layered living bioengineered skin construct. This man had recurrent neuropathic ulcers on the metatarsal heads. Here the baseline ulcer (Panel A) is surrounded by callus, which needs to be removed because it causes further pressure on the ulcer. After debridement, a living bi-layered bioengineered skin construct was applied to the ulcer (Panel B). This living skin equivalent is bi-layered and made up of human keratinocytes and dermal fibroblasts derived from neonatal foreskin. The fibroblasts are embedded in a type I bovine collagen matrix. Slits are often made in the bi-layered bioengineered skin construct, so as to allow the escape of exudate from the wound, or else the “graft” (there is no actual take with these biological constructs) would be uplifted. Overlapping of the living skin equivalent onto the wound edges seems to increase its adherence and prevents it from shifting. The photograph in Panel C was taken 3 days after the application of the construct, and it shows the construct to be firmly in place. Complete healing of the ulcer occurred within 2 weeks (Panel D). At this point, there is no exudate appearing on the dressing. We could not be sure as to whether the living skin equivalent remained on the wound or whether it provided a stimulus for wound repair, but our published PCR data show that the allogeneic cells of these constructs are no longer detectable at 4 weeks. Tissue engineering technology and its application to the treatment of wounds have emphasized that grafts act not only as replacement, but also as cell therapy, capable of delivering growth factors and other stimulatory substances.

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CHAPTER

10 Eiman Wael Abdelaziz , Faisal Gamal Hemeda , Ibrahim Ahmed Elsherbini

Drug Loaded Wound Dressing -

The sequential release of therapeutic agents is of paramount importance for chronic wound healing. - Chronic wounds suffer from delayed angiogenesis, resulting in extreme hypoxia, followed by a reduction in the production of reactive oxygen species by immune cells. As a result, more pro-inflammatory cytokines are secreted to recruit more immune cells. - Continuous infiltration of immune cells without proper healing results in excessive production of proinflammatory cytokines such as MMPs, which will excessively degrade the temporary ECM deposited by cells at the injury site and will prevent tissue regeneration. - To disrupt the impaired cycle of ischemia, reperfusion, and inflammation, sequential and selective release of antiinflammatory agents followed by proangiogenic growth factors, epidermal growth factors, and small molecules has been suggested. - Several factors should be considered in deciding the administration route of therapeutics: 1. The dysfunctional wound bed vasculature reduces the bioavailability of compounds administered orally or intravenously. 2. Some of the drugs can have systemic side effects.

3. The wound environment is rich in various pro-inflammatory cytokines that can deactivate the drugs. 4. Physiological processes are timeconsuming and the administered drugs should be present during that time. - Thus, local delivery of therapeutic agents is compelling compared to systemic delivery since it reduces the undesired side effects such as toxicity or suboptimal delivery. - An optimal drug delivery system should sequentially and selectively release antibacterial agents, growth factors, cytokines, and other small molecules in a controlled way so that the wound would follow the necessary course of healing.

Polymeric drug delivery systems - Nondegradable or biodegradable polymers have been widely used since these systems can be tailored through the physicochemical properties of the polymers as well as various possible encapsulation methods.

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In polymeric systems, the release is affected by parameters such as molecular weight (Mw), glass transition temperature (Tg), crystallinity, solubility and polymer degradation rate. Polymer molecular weight has a direct effect on the Tg, viscosity, crystallinity, mechanical properties, and degradation rate. Polymers with lower molecular weight have a faster degradation rate and higher elastic modulus. This results in higher deformation and pore expansion upon deformation, leading to higher release. In contrast, polymers with higher molecular weight have lower elastic modulus and are less deformable upon degradation, limiting the drug release.

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Studies On Drug Loaded Wound Dressing 1. In Situ HydrogelForming/Nitric Oxide-Releasing Wound Dressing for Enhanced Antibacterial Activity and Healing in Mice with Infected Wounds -

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In recent years, nitric oxide (NO) has gained attention as a novel agent for the treatment of infected wounds as it has the following characteristics: Facilitates wound healing processes such as skin cell proliferation and tissue remodelling. Exerts bactericidal effects via multiple biochemical pathways through the formation of reactive nitrogen species which can interact with various bacterial proteins, DNA, and enzymes to result in bacterial cell death. Has a broad-spectrum antibacterial effect. Effective against drug-resistant bacteria, including MRSA.

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Despite these beneficial effects of NO, its clinical application remains challenging because of its short halflife and gaseous nature. The development of a NO-releasing formulation with a sustained NOrelease and good storage stability is required. A powder dressing that forms a hydrogel in situ maintains a powder state during storage and converts to hydrogel immediately when applied to wounds could be an ideal NO-releasing formulation for the treatment of infected wounds. In this study, a novel in situ hydrogelforming/NO-releasing powder dressing (NO/GP) possessing the benefits of both powders and hydrogels was developed using S-nitrosoglutathione (GSNO), alginate, pectin, and polyethylene glycol (PEG) for the treatment of infected wounds. GSNO is a widely used endogenous NO donor that can generate NO over several hours under physiological conditions. Sodium alginate was selected to form a bio-adhesive hydrogel. In addition, it can absorb wound exudate up to approximately 20-times its weight. Pectin was used to form a hydrogel structure and accelerate the powder-tohydrogel transition. PEG was added to modulate the ability of the formulation to uptake fluid to prevent potential wound drying caused by the excessive absorption of exudate.

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The dressing would have the following properties: 1) Fits the irregular surface of the wound without wrinkles or fluting. 2) Easy to apply to bendable areas of the human body, such as elbows, finger joints, ankles, or wide wound beds resulting from burn and pressure ulcers. 3) Absorb the wound fluid and form an adhesive hydrogel, which protects the wound site from the external environment and maintains a humid environment to aid wound healing.

1) 2) 3) 4) 5) 6)

The ability of NO/GP to form a hydrogel in situ: -

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Rheological studies -

This study will evaluate the Following characterization of NO/GP: The storage stability. In situ hydrogel-forming ability. Rheological properties. NO-release profiles. Antibacterial effects against MRSA and Pseudomonas aeruginosa. The in vivo therapeutic effects of NO/GP were evaluated using a bacteria-challenged full-thickness wound mouse model.

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The hydrogel structure of NO/GP exhibited sufficient adhesiveness, remain stable on the wound surface& resist small shear stress such as gravitational force or brushing against clothes.

NO Release from NO/GP -

The storage stability -

Following its application to the wound, the NO/GP powder was immediately converted to a glittering hydrogel, and more than 50% of the NO/GP powders converted to a hydrogel within 1 min. All of the NO/GP applied was converted to hydrogel within 10 min.

NO release was triggered by absorbed wound exudates. The NO release was calculated by measuring the GSNO decomposition. (Released NO = initial GSNO remaining GSNO) NO released over 24 h without an initial burst release.

Antibacterial effects

Although numerous GSNO-containing hydrogel dressings have been created to promote wound healing, such formulations did not exhibit long-term stability because GSNO hydrolysis is unavoidable in water-containing formulations. Conversely, no significant GSNO decomposition was noted in NO/GP up to 140 days under both (4&37 °C) conditions Since GSNO in the NO/GP remained in a powder state, which was a water-free condition during storage.

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To investigate the antibacterial activity of NO/GP, an in vitro antibacterial assay was performed using the CFU method against MRSA and P. aeruginosa, which are representative drug-resistant gram-positive and negative bacteria. Following incubation for 24 h with or without NO/GP in TSB media, a 6-log reduction in bacterial CFUs was observed in the NO/GP-treated group compared to the GP-treated group against both MRSA and P. aeruginosa.

In Vivo Wound Healing Study (Evaluation of Wound Size Reduction effect) -

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2. A cannabidiol-containing alginate-based hydrogel as a novel multifunctional wound dressing for promoting wound healing

The therapeutic effects of NO/GP were evaluated in mice using the bacteriachallenged full-thickness wound model. The acceleration of infected wound recovery with NO/GP was evaluated by observing morphological changes in the wound and measuring wound size change every 2 days. The NO/GP treatment resulted in a significant reduction in wound size compared with GP treatment and no treatment after 4 days, also the wound size was reduced to less than 20% of the initial size 14 and 8 days after treatment initiation. Conversely, in the GP-treated groups, no significant acceleration of wound healing was observed. Accelerated wound healing in the NO/GP groups can be attributed to the action of NO released from GSNO in NO/GP.

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Conclusions -

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In this study, we successfully developed an in situ hydrogelforming/NO-releasing wound dressing (NO/GP) with a controlled NO-release property and good storage stability for the effective treatment of infected wounds. The results of an in vitro antibacterial study, in vivo antibacterial effects and accelerated wound healing effects suggest that the in-situ hydrogelforming/NO-releasing formulation presented in this study would be a promising alternative to dressings for the treatment of infected wounds.

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Cannabidiol (CBD) was reported to be able to regulate the endocannabinoid system (ECS), which is prevalent in the integumentary system of mammalian species, including mucous membranes and cutaneous. CBD exhibit remarkable efficacy in treating skin disorders due to its unique anti-inflammatory and antioxidant properties. CBD can inhibit the TRPV1 and GPR55 signalling pathways to reduce the release of the pro-inflammatory cytokine CBD can prevent the formation of superoxide radicals that originate from xanthine NADPH oxidase (NOX1 and NOX4) and oxidase (XO), and so effectively reduce the production of reactive oxygen species (ROS). Zn is a trace element in the human body, which is regarded as a cofactor in most enzymatic reactions involved in the wound healing process. Zn2+ ions exhibited broad-spectrum antibacterial activity; therefore, it helps avoid antibiotic abuse. Zn2+ ions can regulate vascular cell viability and promotes angiogenesis via zinc-sensing receptor ZnR/GPR39. Biomaterials containing Zn2+ ions can up-regulate the expression of the vascular endothelial growth factor (VEGF) gene. Therefore, in this study, we fabricated a new cannabidiol-containing alginateZn (CBD/Alg-Zn) hydrogel by incorporating CBD into the crosslinked ion hydrogel of the Alginate and Zn2+ ions.

remained at a relatively stable level, which was attributed to the chelating function between the Zn2+ ions carboxyl groups of SA.

Results of the study: Characterization of hydrogels: -

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As a natural polymer rich in carboxyl groups, alginate might supply a significant number of cross-linking sites to form bridge bonds with Zn2+ ions and serve as the backbone of the hydrogel's 3D network structure. The embedded CBD in the specified concentration range has not disrupted the hydrogel structure The pore sizes of the hydrogels gradually increased with the increase of CBD contents, this may be because CBD, as a small hydrophobic molecule, was embedded in the hydrogels, which caused the crosslink density of the hydrogels to decrease Na+ ions in the SA polymers were replaced successfully by the divalent cation of Zn2+ ions for forming hydrogels The amounts of sulfur originating from ZnSO4 in the Alg-Zn hydrogel were extremely low, which indicated that some residuals in the hydrogel samples were completely removed. The swelling ratios of the CBD/Alg-Zn hydrogels increased as the CBD concentration increased The increase of the swelling ratios of the CBD/Alg-Zn hydrogels should be due to the decrease of the cross-linking density of the hydrogels that was caused by the incorporation of CBD, and this is consistent with the results of SEM The CBD sample maintained a thermally stable state before 150 °C, then showed a rapid decomposition in the temperature range of 170–230 °C The release of zinc ions was quickly transferred to a plateau after incubating for 24 h and then the concentration of Zn2+ ions in the release medium

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Reactive oxygen species (ROS) is physiologically a by-product derived from intracellular metabolism and is produced in large quantities around damaged tissues. A large amount of ROS accumulated in the wound can target and damage DNA and proteins in wound tissue, significantly restrict angiogenesis and cause endothelial dysfunction, severe hindering wound tissue regeneration. Alg-Zn hydrogel showed the lowest DPPH free radical scavenging rate because alginate possesses some antioxidant activity. With increasing CBD concentrations, the DPPH free radical scavenging rates of the CBD/SA-Zn hydrogels were enhanced, due to the high proton donating ability of CBD.

Antibacterial activity of CBD/Alg-Zn hydrogels: -

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Zinc cross-linked hydrogels displayed a strong activity to inhibit the growth and proliferation of bacteria. S. aureus and E. coli were selected to be cultured with different hydrogels. Alg- Zn and CBD/Alg-Zn hydrogels exhibited significant inhibitory effects for E. coli. The antibacterial activity of CBD/AlgZn hydrogels was slightly higher than that Alg-Zn hydrogel. The antibacterial activity of CBD/AlgZn hydrogels was increased in a CBD dose-dependent manner. CBD has a little antibacterial activity.

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In vitro biocompatibility of CBD/Alg-Zn hydrogel: -

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Cross-linked zinc hydrogels are nontoxic. HUVECs and NIH 3T3 cells were selected as cell models for the Live/Dead Cell staining assay and the MTS assay. During the whole of this incubation process, NIH 3T3 cells maintained high cell viability in all the hydrogel groups s and control group, and we did not observe a significant difference. Few dead cells were observed in all hydrogels and the live cells exhibited good proliferation status. The hydrogels were biocompatible, and the embedding of CBD in the hydrogels has no obvious toxic effect on NIH 3T3 cells. For HUVECs, the result of the cell viability test showed that the Alg-Zn hydrogel showed no apparent differences in the cell viability test. Alg- Zn hydrogel showed no obvious differences in cell proliferation compared to the control group. CBD/Alg-Zn hydrogel exhibited lower cell proliferation than the Alg-Zn hydrogel. Embedding of CBD in the hydrogels has an inhibitory effect on cell proliferation of HUVECs. CBD can inhibit the proliferation of HUVECs without inducing cell apoptosis or necrosis through multiple mechanisms Hydrogels with a low concentration of CBD are nontoxic.

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Wound healing study: -

Quantitative RT-PCR analysis: -

To investigate the anti-inflammation function of CBD/Alg-Zn hydrogel, the expression levels of TNF-α, IL-6, and IL-1β were measured by RT-PCR analysis The expression of all pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, were obvious upregulated by Alg-Zn hydrogel. High concentration of Zn2+ (Zn2+ concentration > 15 μM) could induce the pro-inflammatory response. After CBD was embedded into Alg-Zn hydrogel, the expression levels of these pro-inflammatory cytokines were significantly decreased relative, and the expression levels of IL-6 and IL-1β in the CBD/ Alg-Zn group are lower than that of the control group. CBD can inhibit NFκB-mediated inflammatory signalling by stimulating the PPARγ receptor The high expression of VEGF and EGFL6 of HUVECs was considered an essential marker of angiogenesis. Both Alg-Zn and CBD/Alg-Zn hydrogels upregulate the expression of VEGF and EGFL6, which should be due to the angiogenic properties of Zn2+ ions. Zn2+ ion can regulate vascular cell viability and promotes angiogenesis via zinc-sensing receptor ZnR/GPR39. The introduction of CBD in Alg-Zn hydrogel did not affect the angiogenesis activity of the hydrogel.

Researchers have reported that wound dressings with angiogenesis and antiinflammation capability are more beneficial in promoting wound healing

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On the 3rd day, the wound contraction speed of Alg-Zn and CBD/Alg-Zn hydrogels were significantly faster than the control. The result indicated that CBD/Alg-Zn hydrogel has a better treatment efficacy for skin defects. On the 14th day, the remaining wound areas could hardly be observed in the

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Alg-Zn hydrogel group and CBD/AlgZn hydrogel group. H&E staining results showed that all groups displayed obvious regeneration of the epidermis and dermis and the recovery of blood vessels, and some slight inflammatory reaction was also observed on the 7th day. More granulation tissue, regenerated epidermis, and milder inflammatory cell infiltration in the CBD/Alg-Zn hydrogel. More blood vessels were also found in the Alg-Zn hydrogel group, which is attributed to the zinc-containing biomaterials. The CBD/Alg-Zn and Alg-Zn hydrogel groups showed more collagen deposition on the 7th and 14th days. Relatively large number of blood vessels and some hair follicle structures were also observed in the CBD/ Alg-Zn hydrogel group on the 14th day, The apparent difference was not observed between CBD/Alg-Zn and Alg-Zn hydrogel groups.

3. Gentamicin-Loaded Wound Dressing With Polyvinyl Alcohol/Dextran Hydrogel (Gel Characterization and In Vivo Healing Evaluation) -

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Polyvinyl alcohol (PVA) hydrogels prepared with a freeze-thawing method have been studied for biomedical and pharmaceutical applications because of their non-toxicity and good biocompatibility. In this study, dextran and gentamycin were used instead of sodium alginate and other drugs to develop an effective gentamicin-loaded wound dressing with an enhanced healing effect. Gentamicin has been used topically in the treatment of superficial infections of the skin since it is effective against many aerobic Gram-negative and some aerobic Gram-positive bacteria.

Results of the study: -

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Conclusions: - CBD/Alg-Zn hydrogels showed: 1) High swelling ratio. 2) Stable thermal stability. 3) Suitable rheological properties. 4) Good biocompatibility. 5) Antibacterial activity. 6) Angiogenesis properties. 7) Antioxidant activity. 8) Best wound healing effect. 9) Milder inflammatory infiltration. 10) More granulation tissues. 11) More Collagen deposition. 12) Upregulation of the expression of CD31 to promote the formation of blood vessels.

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Increasing the dextran content in the hydrogel resulted in a lower gel fraction. Lesser cross-linked hydrogels showed a higher water uptake because the highly cross-linked structure could not sustain much water within the gel structure. The hydrogel with the drug improved the swelling ability compared to the hydrogel without the drug. Dextran produced less stiff and more elastic hydrogels. Gentamycin in the hydrogel significantly decreased the tensile strength. To estimate the wound healing ability of the hydrogel for the acceleration of wound repair, the PVA/dextran hydrogels were applied to wound spots in the rat dorsum.

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Wounds treated with sterile gauze, the hydrogel with drug, the hydrogel without drug, and the conventional products on various days of postoperation were used on the wound. The wound size reduction was significantly greater in the order of the hydrogel with drug > the hydrogel without drug >conventional product. The hydrogel with the drug greatly enhanced the re-epithelialization rates. Moreover, the hydrogels significantly decreased the granulation tissue areas compared with the conventional product. The hydrogel with the drug significantly improved wound healing compared with the hydrogel without the drug because of the potential healing effect of gentamicin.

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Conclusions: -

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The hydrogel composed of PVA, dextran, and drug significantly improved the wound healing effect compared with the gauze control, the hydrogel without drug, and the conventional product. Thus, it is a potential wound dressing with excellent forming and improved healing effect in wound care.

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4. Mechanical properties and in vivo healing evaluation of a novel Centella asiatica- loaded hydrocolloid wound dressing -

Drug release from hydrocolloids is insufficient owing to the strong linkages of the hydrophobic polymer chain. A novel sodium alginate-based Centella asiatica (CA)-loaded hydrocolloid wound dressing (HCD) providing excellent mechanical properties and improved wound healing. CA is a solid drug that contains three major components which are asiaticoside, asiatic acid and madecassic acid. All these major components are effective in treating abnormal scar formation, systemic scleroderma and keloids by strongly inhibiting the biosynthesis of collagens and acid mucopolysaccharides in carrageenin granulomas. Drug possesses excellent bacteriostatic and anti-inflammatory activity. It has been reported to induce no irritation or damage to the skin. to develop an ideal HCD, various CAloaded HCDs were prepared with suitable ingredients such as sodium alginate, polyisobutylene, SIS, PHR and liquid paraffin using hot melting method Sodium alginate was used as the base of the HCD because of its biocompatibility and excellent hydrocolloid film-forming property.

The following effects of different CAloaded HCDs were evaluated:

Hydrocolloid dressings are frequently employed in wound healing. In these dressings, various elastomers, adhesives and hydrophilic polymers are attached to a semipermeable thin sheet to produce a flat, occlusive and adhesive dressing that possesses the property to form a gel upon contact with wound exudates, thus facilitating moist wound healing.

1) The effect of sodium alginate, styreneisoprene-styrene copolymer (SIS) and petroleum hydrocarbon resin (PHR) on the mechanical properties of CAloaded HCDs. 2) The effect of disintegrants on swelling and drug release.

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3) The in vivo wound healing potentials of the selected CA-loaded HCD in various wound models such as abrasion, excision and infection in comparison with the commercial product.

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Polyisobutylene and SIS hardly affected the mechanical properties, but PHR improved the tensile strength and elongation at break. Disintegrants such as croscarmellose sodium, sodium starch glycolate and crospovidone improved the swelling ratio of the CA-loaded HCD. Furthermore, the CA-loaded HCD without croscarmellose sodium poorly released the drug, but that with 2% croscarmellose sodium showed about 27% drug release in 24 h. In particular, the CA-loaded HCD composed of CA/polyisobutylene/SIS/PHR/liquid paraffin/sodium alginate/croscarmellose sodium at the weight ratio of 1/8/25/25/12/27/2 furnished excellent mechanical properties and drug release. As compared with the commercial product, it offered improved healing effects in excision, infection and abrasion-type wounds.

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Wound healing potential of the CAloaded HCD -

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As compared with the control, quicker and better wound healing in the CAloaded HCD and commercial product likely occurred due to the moist environment at the wound site. A moist environment around a wound has a profound beneficial impact on the physiological process of wound healing as it makes the wound soft and facilitates the migration of fibroblasts and keratinocytes and the distribution of cell growth factors and cytokines. Thus, moist wound healing accelerates epithelialization and the various stages of wound healing. Although there was no significant difference in the healing profiles of the CA-loaded HCD and the commercial product, the former exhibited better healing potential. This positive healing effect of the CA-loaded HCD might be attributed to the presence of sodium alginate in its composition. Sodium alginate has been reported to accelerate the wound healing process in some investigations. CA-loaded HCD enhanced wound healing as compared with the commercial product.

Wound healing potential of the CAloaded HCD was assessed in comparison with the commercial product using the abrasion, excision and infection wound models. The wound size gradually reduced over time due to wound closing. Wound healing was faster and better in the decreasing order: CA-loaded HCD >commercial product > control.

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A novel CA-loaded HCD consisting of CA/polyisobutylene/SIS/ PHR/liquid paraffin/sodium alginate/croscarmellose sodium at a weight ratio of 1/8/25/25/12/27/2 showed excellent swelling, drug release and mechanical properties. As compared to the commercial product, it enhanced the healing effect in excision, infection and abrasion wounds in rats. Thus, this CA-loaded HCD could be a potential candidate for the treatment of various wounds.

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To develop a practical CA-loaded HCD, further study on its clinical test will be performed with human subjects.

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5. Polyphosphazene and NonCatechol-Based Antibacterial Injectable Hydrogel for Adhesion of Wet Tissues as a Wound dressing -

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Wound dressings with excellent adhesiveness, antibacterial, selfhealing, hemostasis properties, and therapeutic effects have great significance for the treatment of acute trauma. Bioadhesive hydrogels have strong adaptability that they can be in situ formed, attach to and fill irregularly shaped defects for stopping bleeding and accelerating wound healing. Therefore, they gained great attention as ideal alternatives or adjuncts to sutures for closing defect organs. The highly adhesive wound dressings can quickly attach to wounds and seal the bleeding site in the case of emergency bleeding. The body fluids (blood and mucus), a thin hydration layer or contamination on the substrate, prohibits intimate contact between the bioadhesive and the surface, creating an obstacle for achieving satisfying wet adhesion. In order to achieve efficient wet adhesion, lots of wet adhesives have been designed by simulating a catecholic amino acid present in the adhesive protein glue, 3,4-dihydroxyL-phenylalanine. So far, numerous mussel-inspired catechol-based wet adhesives have been reported, opening a pathway for the treatment of acute trauma. However, catechol-based hydrogels are

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easily oxidized, which limits their applications. Here, the design of a polyphosphazene and non-catechol-based antibacterial injectable hydrogel is reported as a multifunctional first aid bandage. Inspired by barnacle cement proteins, a series of dynamic phenylborate esterbased adhesive hydrogels are prepared by combining the cation–π structure modified polyphosphazene with polyvinyl alcohol. The inherent antibacterial property, anti-mechanical damage, and hemostatic behaviour are investigated to confirm the multi-functions of wound dressings. The catechol groups undergo various types of interactions, such as 𝜋–𝜋 stacking, cation–𝜋 interaction, hydrophobic interaction, hydrogen bonding, and Michael addition. It was found that the catechol group is sensitive to pH, oxidation, and temperature, which made catecholbased wet adhesives unreliable for many practical applications. In attempts to overcome these drawbacks, research progress on noncatechol-based adhesives, including dry-crosslinking mechanism, dynamic covalent bond, hydrogen bonding, topological adhesion, electrostatic interaction, etc. Dynamic chemical bonds in the hydrogel can effectively dissipate energy and improve the hydrogel’s interfacial adhesion and bulk cohesion. The synergy of multiple adhesion mechanisms can enhance the adhesion and cohesion strengths. Herein, a series of non-catechol-based adhesive hydrogels were prepared by introducing the synergy of multiple noncovalent adhesion mechanisms.

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The phenylboronic groups were grafted onto poly(N, Ndimethylethylenediaminephazene) (PDAP) to form a polycationic polymer with inherent antibacterial properties and cation–𝜋 structures. By mixing the polyvinyl alcohol (PVA) solution and polymer solution that is modified with phenylboronic group, the formed dynamic boronic ester bonds can serve as the crosslinking points of the 3D network of the PPBA-PVA hydrogels. The regions of hydrogen bonding, dynamic chemical bonding, 𝜋–𝜋 stacking and cation–𝜋 interaction in the PPBA-PVA enable the hydrogels to heal quickly after being destroyed. The results of wound closure, histopathological examinations and hemostatic properties were evaluated in vivo to investigate the therapeutic effects of PPBA-PVA dressing in the full-thickness skin defect model.

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The results were as follows: -

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1. Thermal stability Thermogravimetric analyzer (TGA) was used to determine the thermal stability of hydrogels. All samples were basically decomposed at temperatures above 1000 °C, indicating that the hydrogels had good thermal stability and could form a stable cross-linking network.

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2. Swelling rate Cationic PPBA-PVA showed good solubility in pure water. The maximum swelling rate reached 122 ± 12%. As for the PBS solution, due to the exchange between water molecules inside the PPBA-PVA hydrogels and ions of the external solution.

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Under physiological conditions, the hydrogels maintained a low expansion rate under the ionic strength of the human body and the undesirable volume expansion during use, which caused adhesion failure. The hydroxyl groups of PVA are dense and could provide abundant hydrogen bonds in the hydrogels, dynamic chemical bonds together with dense hydrogen bonds leading to the unique mechanical and self-healing properties of PPBA-PVA hydrogels. PPBA20-PVA hydrogel can maintain the swelling balance for a long time after a small amount of water loss in the first 0.5 h. 3. Morphology As shown in the above figure, PPBA20- PVA could be uniformly packaged in a syringe and pushed out continuously through a 0.6 mm needle, and maintain good morphology in deionized water and PBS solution. Good fluidity and mechanical properties made it have broad application prospects in biomedical applications. In addition, we can also draw any needed graphics by using PPBA20- PVA hydrogel. The morphologies of hydrogels were observed by scanning electron microscopy (SEM), and all the hydrogels showed porous structures. Traditional hydrogel wound dressings would suffer frequent wear and bending deformation when applied to joints, which would cause abrasion and even structural fracture of hydrogels. Therefore, self-healing hydrogels as new wound dressings can rapidly recover after being destroyed, greatly improving the service life and stability of the hydrogels.

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4. Adhesiveness The adhesive can quickly close the bleeding site and isolate the wound from external pathogenic microorganisms. The adhesive hydrogels are needed to avoid causing secondary damage to the wound after peeling. 12 h of efficient adhesion was able to supply enough pre-hospital time for acute trauma. Compared with the amount of bleeding in the untreated group, PPBA-PVA hydrogels treated groups had a significant decrease in both the time to hemostasis and the amount of bleeding.

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5. Biocompatibility The Live/Dead staining and MTT assay were used to indicate the cell biocompatibility, of which the live and dead cells were stained with green and red fluorescence, respectively. It was found that after being treated with 25, 50, 75, and 100 μg mL−1 of hydrogels extract, the majority of L929 cells presented normal morphology and exhibited a similar proliferation trend as the control group.

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of polymer PPBA20, PPBA30, and PPBA40 by using the minimal inhibitory concentration test (MIC), the gram-negative bacteria Escherichia coli was used as a research model. The higher grafting ratio of QAs induced the polymer to a higher density of positive charge, which made the electrostatic interaction between PPBA and E. coil more intense. However, at low concentrations, PPBA20 showed stronger antibacterial activity than PPBA30 and PPBA40. This may be caused by the different hydrophilic and hydrophobic properties of PPBA due to different grafting densities of the cation–𝜋 structure. The antibacterial ability of PPBA-PVA hydrogels mainly depends on the QAs in the hydrogel skeleton, so the bacteria ruptured by electrostatic interaction.

7. Healing ability The rapid healing ability of PPBAPVA was determined by the three factors that affect the healing process of the hydrogels: 1) The abundant hydrogen bonding interaction provided by PVA in the hydrogels network 2) the 𝜋–𝜋 interaction between the benzene ring and the benzene ring at the healing interface -

6. Antibacterial properties Polyphosphazenes modified with QAs have been proven to have excellent antibacterial properties. The positive charged tertiary amine groups and the QAs can inhibit the growth of bacteria through electrostatic interaction, which induced PPBA to obtain a good inherent antibacterial property. In this study, due to the high density of cationic QAs, PPBA-PVA hydrogels can inhibit the bacteria through electrostatic interaction. We first evaluated the antibacterial properties

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3) The dynamic formation between the benzene boric acid groups and the hydroxyl group of the PVA at the healing interface. - The wound healing performance of PPBA-PVA was investigated in fullthickness skin defect models (Figure 7b). - (Figure 7a, c) showed the wound contraction of commercial films (Tegaderm) (control), PPBA20-PVA, PPBA30-PVA, and PPBA40- PVA groups on the 0th day, 3rd day, 5th day, 7th day, 9th day, and 11th day, respectively. The wound contraction of the PPBA40-PVA hydrogel group had the advantage over other groups. - In the early stage of wound healing (