Wound Management for the Advanced Practitioner

WOUND MANAGEMENT

for the

ADVANCED PRACTITIONER

WOUND MANAGEMENT

for the

ADVANCED PRACTITIONER

Edited by

TERRY SWANSON,

MARGO ASIMUS, and BILL MCGUINESS

IP COMMUNICATIONS

Melbourne 2014

IP Communications, Pty. Ltd.,

PO Box 1001

Research, Victoria, 3095

Australia.

Phone: +61 0423 269 353

E-mail: ipcomm@bigpond.com

www.ipcommunications.com.au

© Terry Swanson, Margo Asimus, and Bill McGuiness

Authors retain copyright for their contributions to this volume

First published 2014

This book is copyright. Subject to statutory exemption and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of IP Communications, P/L.

ISBN: 978-0-9872905-3-3

National Library of Australia Cataloguing-in-publication data

Title:  Wound management for the advanced practitioner/Terry Swanson, Margo Asimus, and Bill McGuiness, editors.

ISBN: 9780987290533 (paperback)

Notes: Includes bibliographical references and index.

Subjects: Wounds and injuries—Textbooks.

Wounds and injuries—Management.

Wounds and injuries—Treatment.

Other Authors/Contributors:  Swanson, Terry, editor.

Asimus, Margo, editor.

McGuiness, Bill, editor.

Dewey Number: 617.1

Edited by Gillespie & Cochrane Pty. Ltd., Melbourne

Text design by Club Tractor Production Services, Melbourne

Typeset by Desktop Concepts Pty. Ltd., Melbourne

Cover design by Anne-Marie Reeves, Melbourne

Cover image: © Ocskay Mark/Dreamtime.com

Indexed by Mary Russell, Melbourne

Printed by BPA Print Group Pty. Ltd., Melbourne

Supplement to book: On the publisher’s website, www.ipcommunications.com.au, can be found a list of wound care products with details of manufacturers and distributors.

Contents

Preface

Dedication

About the editors

About the contributors

List of colour plates

Part 1 Core elements of effective wound management

Chapter 1 The science of wound healing

AJ Cowin and J Waters

Chapter 2 Factors that inhibit wound healing

N Ruzehaji and AJ Cowin

Chapter 3 Assessment

Terry Swanson

Chapter 4 Outcome measures

Margo Asimus

Appendix 4.1 Healable wound cost effectiveness calculation template

Chapter 5 Evidence-based practice

Jason Wasiak and Anneliese Spinks

Chapter 6 Undertaking research

Bill McGuiness

Part 2 Wound bed preparation and management

Chapter 7 Diagnostic investigations

Michael Woodward and Terry Swanson

Chapter 8 Assessment and management of non-viable tissue

Wendy White and Margo Asimus

Appendix 8.1 Debridement modality matrix

Chapter 9 Infected wounds

Sue Templeton

Chapter 10 Modern dressings and technologies

Terry Swanson

Chapter 11 Pharmacology in wound management

Kerrie Coleman and Lisa Nissen

Chapter 12 Acute wounds

Jennifer Byrnes and Tabatha Rando

Part 3 Types of wounds

Chapter 13 Venous leg ulceration

Bill McGuiness

Chapter 14 Arterial and mixed arterial-venous ulceration

Denise Findlay

Chapter 15 Inflammatory ulcers

Di Smith

Chapter 16 Unusual wounds

Jan Rice and Terry Swanson

Chapter 17 Pressure injury

Robyn Rayner, Margo Asimus, and Pui Ling (Iris) Li

Chapter 18 The high-risk foot

Kerry May and Paul Wraight

Part 4 The professionalisation of wound management in Australia

Chapter 19 Evolution of wound management in Australia

Keryln Carville

Chapter 20 Wound management education in Australia

Anne Purcell, Cathy Watson, and Sue Quarmby

Index

Preface

Wound management is increasingly recognised as a specialised area of practice. A continuum of knowledge exists from the very fundamental to the advanced practitioner, but while a number of basic reference texts are available, little exists for the developing and advanced practitioner. Wound Management for the Advanced Practitioner provides a reference source to clinicians functioning at an advanced level in wound management and presents in accessible form the knowledge a practitioner would obtain in an advanced wound management course or master class.

While the general principles of wound care remain the same – to prevent infection, treat pain, and encourage granular deposition – the management of wounded clients is becoming increasingly more complex. Advances in wound care products, surgical interventions, and social support options create an often confusing array of knowledge for healthcare practitioners wishing to provide an advanced level of service for this patient cohort. Drawing from the knowledge of experienced clinicians and from available research, the text examines aspects of healing and the implementation of complex interventions for a variety of wound types. The discussion of healing examines the entire process from the molecular level to that of social and contextual impacts. Complex interventions that encompass pharmacological therapies, surgical procedures, and diagnostics related to wound management are described to inform and support both health professionals working in wound management at an advanced level and those seeking to advance their basic wound management knowledge.

It is anticipated that the text will become the guide for clinicians currently employed in key wound management roles and those seeking information and skills necessary for a nurse practitioner, advanced practice nurse, general practitioner, and allied health professional role in Australia. This specific information is becoming progressively more essential.

Dedication

To pay tribute to him for his commitment to improving wound-management practice and education, and for his unwavering support for and mentoring of many Nurse Practitioners and Advanced Practice Nurses, over twenty-five years, we dedicate our book to Professor Donald MacLellan, Director, Surgery, Anaesthesia and Critical Care, NSW Agency for Clinical Innovation.

The editors and specialist chapter-authors

About the editors

Margo Asimus (NP, RN, RM, STN, Cert IV Training & Assessment, NPWM) commenced her career in wound management as a stomal therapist in 1995. By 1996 she had founded a regional wound interest group to promote education in the Hunter Valley area. She is the current President of the Australian Wound Management Association (AWMA) and immediate past president of the New South Wales branch of AWMA. In 2009 Margo was acknowledged as a clinical leader for her work in developing a pressure injury prevention program which went on to win the NSW Clinical Excellence Commission Award. She was again recognised for her outstanding work in wound management by winning the Health Districts Clinical Leader of the Year award in 2011. The esteemed award of Australian Nurse Practitioner of the Year was bestowed on her in 2013. Her research in pressure injury prevention has been published and presented nationally and internationally. Her role involves providing an advanced wound management service in community care, aged care, and a rehabilitation facility in the Hunter region of New South Wales.

Associate Professor Bill McGuiness (Dip T, Bed., MNS, PhD, RN, FAWMA) is Head of the La Trobe University School of Nursing and Midwifery and Director of the Alfred Clinical School. He has an appointment as a Wound Clinical Nurse Consultant at The Alfred Hospital and manages a nurse-led outpatient clinic for patients suffering from leg ulceration. Bill is a former President of the Australian Wound Management Association. He has been involved in nursing education since 1983 as both a hospital and university-based teacher. His research interests include the management of chronic wounds, clinical predictors of slow-to-heal wounds, and the prevention of pressure injuries in the frail aged and critical care clients.

Terry Swanson (RN, PG Cert (Periop), MHSc, NP, FAWMA, FMACNP, NPWM) is a Fellow of the Australian Wound Management Association and Life Member of Victorian Branch in recognition of her contribution to the field of wound management at a state, national, and international level. She is the current Chair of the International Wound Infection Institute and Nursing Representative of AWMA. Terry has held positions of responsibility for several state and national nursing and wound related organisations. Her research interests have focused on wound infection and Low Frequency Ultrasound Debridement. She has worked in the field of wound management since the early 1990s and currently manages an outpatient clinic and hospital wound service at South West Healthcare in Warrnambool, Victoria.

About the contributors

Jennifer Byrnes (RN, STN, WMNP, MN (NurPrac), Grad Cert STN, Cert Wound Mgt) has worked at Royal Darwin Hospital since 2002 as a wound management nurse and stomal therapist, and in 2009 she became the first Nurse Practitioner appointed in the Northern Territory. In this time she has dealt with numerous unusual and challenging wounds, and was also involved in advising and implementation of wound management for mass trauma cases such as the second Bali bombing, 2005, and the Timor crisis in 2006. Professional positions held include President of Australian Wound Management Association NT Branch, NT Chapter Chair for the Australian College of Nurse Practitioners (ACNP), and NT State Representative for the Australian Association of Stomal Therapy Nurses (AASTN).

Keryln Carville (RN, STN(Cred), PhD) is Professor of Primary Health Care & Community Nursing at Silver Chain and Curtin University, Western Australia. Keryln has extensive clinical experience and is committed to research and education within the domains of wound and ostomy care. Keryln was appointed an Inaugural Fellow of the Australian Wound Management Association in 2006. She is Chair of the Australian Pressure Injury Advisory Panel, Chair of the AWMA Australian Wound Standards Committee, and Chair of the Evidence Committee of the International Wound Infection Institute.

Kerrie Coleman (Dip ApSc, BNSc, MN clinical (wound management), MN (Chronic Disease)) is a Nurse Practitioner in wound management and is a part of the multidisciplinary Skin Integrity Service at the Royal Brisbane & Women’s Hospital. Kerrie has extensive clinical experience in wound management and quality-of-life and chronic wounds. Kerrie has a focus on improving standards of holistic patient-focused evidence-based care and is currently involved in research projects involving pressure injury and nutrition, venous leg ulcers, and diabetic wound healing and hyperbaric therapy. In 2009 Kerrie was honoured with an Excellence in Clinical Practice Improvements award for the district in relation to her work in wound management and research.

Allison Cowin (BSc (Honours), PhD) is Professor of Regenerative Medicine at the Mawson Institute, University of South Australia. She is a leading researcher in the area of wound healing and scar formation. Professor Cowin was the Founder and inaugural President of the Australasian Wound & Tissue Repair Society and is joint editor of Wound Practice & Research. She is on the Editorial Advisory Board of Wound Repair and Regeneration, is an NHMRC Senior Research Fellow, and a Fellow of the Australian Wound Management Association.

Dr Denise Findlay (MBBS, MEd, FRACGP) is a GP and medical educator working in GP training. She has had a special interest in wound management for over 20 years and for most of that time has coordinated a multidisciplinary wound clinic. She has been involved in a number of national randomised controlled trials of wound dressings, and conducts nurse and GP education workshops focusing on wound management in primary care. Denise has also written wound articles for numerous journals and a chapter for The Oxford Textbook of Family Practice.

Kerry May is the Allied Health Director – SouthEast Sector at Monash Health, and until April 2012, the Podiatry Manager and Diabetic Foot Unit Coordinator at the Royal Melbourne Hospital for over 10 years. Kerry has a Bachelor of Podiatry, a Graduate Diploma in Vocational Education and Training, and a Master of Gerontology. Her role at the Royal Melbourne Hospital involved establishing a Diabetic Foot Unit with Associate Professor Paul Wraight to ensure that people with diabetes-related foot complications were provided with evidence-based management by a multidisciplinary team passionate about limb preservation and patient quality of life across the continuum of care. Kerry has represented Allied Health on the Australian Wound Management Association, and is a founding member of the Advanced Practicing Podiatrist – High Risk Foot Group.

Lisa Nissen (BPHARM, PhD, FHKAPH, FSHP, FPS) is Professor and Head of the School of Clinical Sciences, Queensland University of Technology. She has worked in both rural and metropolitan hospital and community pharmacy practice. Her research focuses on the Quality Use of Medicines in the wider community, and the expansion of roles for pharmacists, including pharmacist prescribing and the expansion of pharmacy practice into other cognitive service delivery areas, including sleep and pain. Her key practice philosophy is based on integrated, patients-focused, team-based care. Lisa was the 2002 PSA Young Pharmacist of the Year and the 2008 Pharmacist of the Year. Lisa was awarded Australian University Teaching Excellence awards in 2008 and 2013.

Pui Ling (Iris) Li currently works as a Co-ordinator of the Wound Management and Pressure Injury Prevention Program in the Hunter New England Local Health District, New South Wales. She has been involved in the Pressure Injury Prevention Program since 2009, which won the NSW Clinical Excellence Commission Award in 2009. Iris completed her nursing Masters degree in 2005. She has had papers on pressure injury prevention published in peer-reviewed journals. She is also a Conjoint Lecturer of the University of Newcastle.

Anne Purcell (RN, RM, NP, BN, MN (Nur Prac), PhD candidate) commenced her nursing training at the Royal Alexandra Hospital for Children, Sydney, New South Wales, in 1976. Following a background in high dependency and medical paediatrics, Anne moved into community nursing due to her passion for the speciality of wound management. After completing advanced practice studies with the Wound Foundation of Australia she followed with a Bachelor of Nursing and Masters of Nursing (Nurse Prac) with the University of Newcastle, New South Wales. Anne has been authorised as a Nurse Practitioner for seven years in the speciality of wound management and is currently practising within the Central Coast Local Health District Community Nursing Service and sub-acute facilities. Anne is undertaking a PhD with Griffith University Gold Coast, Queensland, investigating topical anaesthesia and painful chronic leg ulcers.

Sue Quarmby is a nurse educator with extensive experience in wound management. She has been instrumental in establishing and implementing moist wound management projects in several tertiary hospitals throughout Australia and South Africa, and has been conducting postgraduate courses in wound management through various institutions for the past fifteen years. Sue has been a long standing AWMA committee member and was a co-founder of the AWMA Education and Professional Development Sub-Committee. Sue is currently coordinating a Short Course Program at University of Tasmania School of Medicine.

Tabatha Rando (RN, MNP, Grad Dip CHN, Grad Cert STN, Cert Wound Mgt, Dip FLM, Cert IV WAT) is a dynamic registered nurse who has worked as a Clinical Nurse Consultant in Wound Management for over 16 years, in community nursing and in the acute, subacute, and aged healthcare sectors in Victoria. In 2010, she was appointed to a senior Clinical Governance position within the Royal District Nursing Service in South Australia. Tabatha is a past President of the Wound Management Association of Victoria, and is currently the National Vice-President of the AWMA. She has also served on the AWMA as the National Membership Secretary. As an author and invited speaker locally, nationally, and internationally, she has a focus on improving standards of holistic person-centred evidence-based care.

Robyn Rayner (RN, BSc (Nursing), Postgrad Health Admin, Master Wound Care) is employed as an Education Project Officer for WoundsWest in Western Australia and coordinates the Silver Chain Bunbury Community Wound Clinic. She is a sessional tutor at Monash University for the Masters of Wound Care Program. Robyn is a member of the Australian Wound Management Association (AWMA) Restructure Committee and the Venous Leg Ulcer Guideline Development Group. She was employed by the Australian Pressure Ulcer Advisory Panel to undertake a comprehensive review of the literature and compile the evidence for updating the current Australian Pressure Ulcer Guidelines. Robyn has numerous publications to her credit.

Jan Rice is a Registered Nurse with over 35 years’ experience in surgical nursing. In 2005 Jan co-authored a textbook: Plastic and Reconstructive Surgical Nursing. In 2006 Jan was awarded Fellowship to the Australian Wound Management Association (FAWMA). She chairs the Education group within the APUAP guideline committee, is a member of the AWMA Educational and Professional Development sub-committee, and of the Venous Leg Ulcer Guidelines Development sub-committee, and past President of Wound Management Association Victoria. She obtained a Masters in Wound Care in 2009 and currently runs her own consultancy business, offering wound care consultation, mostly in aged-care settings, but she also runs a clinic in a large medical centre in Melbourne. She is and has been an Interplast volunteer for over 15 years.

Nadira Ruzehaji (BAppSc (Podiatry), BSc (Hons), PhD) has 10 years’ of podiatric medicine experience, which includes treatment of patients with delayed wound healing. This stimulated her special interest in understanding more about the regulation and mechanisms involved in wound healing and led to her decision to return to post-graduate studies in 2007. She obtained her PhD in the wound healing laboratory of Professor Allison Cowin at the Women’s & Children’s Health Research Institute in 2013. Nadira is currently employed as a postdoctoral research associate in the Institut Cochin, INSERM, Paris.

Dianne Smith (MB BS (Qld) 1977, Graduate Diploma in Family Medicine (Monash) 2000) has been a Senior Medical Officer in the Primary Care Unit of the Emergency Medicine Department at the Royal Brisbane and Women’s Hospital for the past 18 years. Her prior training and work has been in general practice. Dianne heads the hospital’s Multidisciplinary Chronic Wound Clinic. This clinic provides an average of 1700 wound consultations a year. Dianne studied dermatology in her Postgraduate Diploma in Family Medicine, which was completed in 1999. She has been an active member of QWCA and AWMA since 1998.

Anneliese Spinks is a research scientist at CSIRO, and concurrently holds an Adjunct Senior Research Fellow position at Griffith University. She completed her PhD in Public Health at the University of Queensland in 2007. Anneliese has a strong interest in the social and environmental determinants of health and wellbeing, with a particular emphasis on the multiple barriers faced by vulnerable populations. During her career, Anneliese has developed strong expertise in community and population-based research methodology, including the implementation of longitudinal and cross-sectional studies. She also has experience with large administrative data sets and translating existing data into meaningful outcome indicators.

Sue Templeton is currently the Nurse Practitioner Wound Management for RDNS SA Ltd. Sue’s career in wound management began in 1987. She has extensive experience in hospital and community sectors managing individuals with a variety of acute and chronic wounds. Sue was President of the Australian Wound Management Association South Australia (AWMA(SA)) 2009–2012 and Vice President of the Australian Wound Management Association (AWMA) from 2010 to 2012. Sue delivers clinical care to individuals with wounds, provides clinical consultancy services, develops and delivers education to health practitioners in a variety of settings, develops policies and tools, publishes and presents, and is involved with several significant projects and boards at a local, state, and national level. She is passionate about improving quality of care and achieving optimal outcomes for all persons with a wound.

Jason Wasiak has completed post-graduate courses in intensive care, adult education, and epidemiology. He has published in the area of burns care and evidence-based medicine. He has a wealth of experience in systematic review methodology and has published a number of Cochrane systematic reviews. He also has a strong interest in bridging the gap between research theory and clinical practice in a hospital setting.

James Waters (BBiotech (Honours), PhD) completed undergraduate and post-graduate studies in biotechnology and molecular biology at Flinders University (Adelaide, Australia). Dr Waters was then employed as a postdoctoral research associate at Durham University (Durham, UK) where his research interests included hair follicle development, epithelial stem cell biology, and epithelial reprogramming. Dr Waters was a postdoctoral researcher in the Wound Healing Laboratory at the Women’s and Children’s Health Research Institute, Adelaide, where he investigated the mechanistic role of Flightless I in wound healing. He currently studies Dental Science at the University of Adelaide.

Cathy Watson (RN, RM, NP, BA, Post Grad Dip in Adv Nursing (Women’s Health), MCHN, MNSc (Nurse Practitioner) PhD) completed her nursing training at St Vincent’s Hospital in 1985. She has had a wide experience in general and midwifery nursing, and enjoyed working in remote locations in Australia and overseas. She now works as a women’s health nurse practitioner at the Royal Women’s Hospital in Melbourne, and is involved in research at the University of Melbourne.

Wendy White (MWoundCare, BEd, RN, Plast. Cert. MACN, FAWMA) is an Advanced Practitioner and educator in New South Wales. She is an invited expert on advisory and working groups and has contributed to international consensus documents specific to minimising wound-related pain and optimising wellbeing for those living with wounds. She has served on Australian Wound Management Association (AMWA) state executive committees, National Education sub-committees, and was Chair, Scientific Program, 9th National AWMA Conference. She actively promotes a person-focused, interdisciplinary approach in the prevention and care of those with or at risk of wounds. Wendy is a recipient of an AWMA Fellowship in recognition of her contribution to clinical practice, education, research, and leadership in wound management throughout Australia and the Asia Pacific.

Associate Professor Michael Woodward is Head of the Wound Management Clinic at Austin Health in Melbourne. He is a specialist in geriatric medicine with major interests in wound management, quality use of medications, nutrition, dementia, and sleep. He is also head of Aged Care Research at Austin Health and is involved in several research trials of new therapies for chronic wounds, especially leg ulcers. He is Immediate Past President of the Australian Wound Management Association, which represents 3000 of Australia’s experts in wound management and has a very active annual Wound Awareness Week.

Paul Wraight is a Clinical Associate Professor of the University of Melbourne and Head of the Diabetic Foot Unit at the Royal Melbourne Hospital. After specialising as an endocrinologist, Paul completed his PhD into ‘Improving clinical outcomes for patients with diabetes related foot complications’. He continues to undertake and publish clinical research in the area of the diabetic foot. He is currently the Australian representative for the International Working Group of the Diabetic Foot and is chair of the Australian Diabetic Foot Network, a working group of Australian Diabetes Society.

List of colour plates

Plate 1 A critically colonised wound that shows scattered slough on an undulating moist surface with pale granulation and a slightly macerated periwound. The flash reveals epidermal tissue on some of the wound edges. (Margo Asimus)

Plate 2 Newly re-epithelialised tissue. (Terry Swanson)

Plate 3 Healthy granulation with epidermal tissue at edges. (Terry Swanson)

Plate 4 Hypergranulation tissue. (Terry Swanson)

Plate 5 Friable granulation tissue. (RDNS SA Inc)

Plate 6 Gangrenous second toe with a combination of dry and moist necrotic and non-viable tissue. (Margo Asimus)

Plate 7 Dry necrotic tissue on right great toe. (Terry Swanson)

Plate 8 Wound with 100% slough. (Margo Asimus)

Plate 9 Infected knee incision. (Terry Swanson)

Plate 10 Large haematoma on a leg that required a surgical evacuation and skin graft. (Terry Swanson)

Plate 11 Healthy muscle in a Grade 4 pressure injury on the buttock. (Terry Swanson)

Plate 12 Exposed tibia and fibula of the leg. (Terry Swanson)

Plate 13 Exposed tendon on hand. (Terry Swanson)

Plate 14 Macerated hand. (Terry Swanson)

Plate 15 Eschar detaching (separating). (Margo Asimus)

Plate 16 Eschar non-detaching (non-separating). (Margo Asimus)

Plate 17 NVT and haematoma following pre-tibial laceration. (Margo Asimus)

Plate 18 Extensive NVT on an ischaemic limb (pre-amputation). (Margo Asimus)

Plate 19 (a) Prior to low-frequency ultrasound debridement, and

(b) the same wound after low-frequency ultrasound debridement. (Margo Asimus)

Plate 20 Erythema surrounding a wound. (RDNS SA Inc)

Plate 21 Purulent exudate. (RDNS SA Inc)

Plate 22 Fluorescent green discolouration of dressings typical of Pseudomonas aeruginosa. (RDNS SA Inc)

Plate 23 Cellulitis. (RDNS SA Inc)

Plate 24 Skin flap to hand with sutures intact. Note the healthy colour and viability of the flap. (Terry Swanson)

Plate 25 (a) Traumatic amputation of fingers in a farming accident. Note fractured bone, debris, vessels, and tendons. (Terry Swanson)

(b) Reattached thumb and flap to hand. Extensive occupational therapy is required for maximum functional activity. (Terry Swanson)

Plate 26 Epidermal loss on back due to abrasion from motorcycle accident. (Terry Swanson)

Plate 27 STAR skin tear classification system (Silver Chain Nursing Association & Curtin University School of Nursing and Midwifery)

Plate 28 Bilateral venous disease with weeping legs, ulceration, chronic inflammation, and slight ridging from compression therapy. (Margo Asimus)

Plate 29 Haemosiderin staining of the left leg. (Terry Swanson)

Plate 30 Ankle flare. (Terry Swanson)

Plate 31 Varicose veins. Note the difference between the legs. (Terry Swanson)

Plate 32 Hyperkeratosis. (Terry Swanson)

Plate 33 Lipodermatosclerosis. (Terry Swanson)

Plate 34 Ischaemic (arterial) ulcer. (Denise Findlay)

Plate 35 Venous ulcer. (Denise Findlay)

Plate 36 Mixed arterial-venous ulcer on the ankle. (Denise Findlay)

Plate 37 Necrotic toe ulcers. (Denise Findlay)

Plate 38 Ischaemic heel ulcer. (Denise Findlay)

Plate 39 Small vessel leucocytoclastic vasculitis on foot. Typical presentation of lesions at varying stages of inflammation, ulceration, and haemosiderin staining. (Terry Swanson)

Plate 40 Classic presentation of pyoderma gangrenosum with the purple wound edges. (Terry Swanson)

Plate 41 Stomal and periwound pyoderma gangrenosum as well as wound dehiscence. (Terry Swanson)

Plate 42 Bullous pemphigoid on the feet. Note the new fluid-filled blister and resolving blisters on both feet. (Terry Swanson)

Plate 43 Scleroderma of the hand with an ulceration and contraction of the fingers. (Terry Swanson)

Plate 44 Epidermolysis with squamous cell carcinoma lesions. Note the loss of toes due to scarring and amputations. (Terry Swanson)

Plate 45 Hidradenitis suppurativa of the axilla. Classic appearance of puckered skin, tunnelling, and pus formation. (Terry Swanson)

Plate 46 Gout of the hand with tophi on the fingers. Note ulcerations on several fingers. (Terry Swanson)

Plate 47 Moisture lesions on buttocks, with epidermal loss not on bony prominences and Grade 1 pressure injury. (Terry Swanson)

Plate 48 Patient with kyphosis and decreased mobility who developed a Grade 3 pressure injury on her thoracic spine. (Terry Swanson)

Plate 49 Grades 2 and 3 multiple pressure injury areas with deep tissue injury on left periwound. (Terry Swanson)

Plate 50 Significant dark tissue noted after debridement of the heel, suggesting deep tissue injury. (Terry Swanson)

Plate 51 Necrotic plug prevents staging of this heel pressure injury. (Margo Asimus)

Plate 52 Pressure mapping image of 80 kg male

(a) lying with buttocks in contact with an ambulance vinyl mattress with a 55° head elevation. (Margo Asimus)

(b) lying with buttocks in contact with a repose mattress on top of an ambulance vinyl mattress with a 55° head elevation. (Margo Asimus)

(c) lying with buttocks in contact with an ambulance vinyl mattress with a 75° head elevation. (Margo Asimus)

(d) lying with buttocks in contact with a repose mattress on top of an ambulance vinyl mattress with a 75° head elevation. (Margo Asimus)

Plate 53 Person with diabetic neuropathy. Note the claw toes and bleeding under the great toenail secondary to high foot pressures. (RMH Medical Illustration Department)

Plate 54 (a) Foot of a person with diabetic neuropathy. This foot demonstrates a Charcot deformity (stable) and areas of high plantar pressures (callus with underlying bleeding). (RMH Medical Illustration Department)

(b) Medial view of same foot demonstrating Charcot deformity and prominent first metatarsophalangeal joint – deformities that are secondary to neuropathy. (RMH Medical Illustration Department)

Plate 55 Bleeding under callus due to high plantar pressures. This is of extreme concern as this will quickly progress to skin breakdown and a wound if the pressure is not off-loaded. (RMH Medical Illustration Department)

Plate 56 Critical ischaemia and infection from a penetrating injury. (RMH Medical Illustration Department)

Plate 57 This is bone protruding from the toe of a person with diabetes. A clinician should have a high index of suspicion for osteomyelitis where bone is visible in a wound. (Terry Swanson)

Plate 58 This is an example of ‘mal perforans’ in a person with diabetes. Note the necrotic plug in the wound and the multiple signs of infection. (Terry Swanson)

Plate 59 Epithelising wound under the first metatarsophalangeal joint in a person with diabetes. This developed secondary to high plantar foot pressures. (RMH Medical Illustration Department)

Plate 60 Wound on a toe apex that developed secondary to pressure from toe deformity and neuropathy. (RMH Medical Illustration Department)

Plate 61 This is an example of a person with diabetes, peripheral artery disease, and a foot infection (Terry Swanson).

Part 1

Core elements of effective wound management

Chapter 1

The science of wound healing

AJ Cowin and J Waters

INTRODUCTION

Our bodies are encased by the skin and its appendages (hair, nails, glands etc.), which provide a protective barrier that keeps microbes out and essential body fluids in.¹,²,³,⁴ The skin receives daily assaults, including scratches, wounds, and harmful ultraviolet radiation. It mitigates these attacks by undergoing continual self-renewal to repair damaged tissue and replace old cells. The relatively tough exterior of the skin and the softer, elastic padding of the lower layers of the skin also help to shield more delicate parts of the body from physical injury by absorbing or deflecting natural physical assaults that would otherwise damage the comparatively fragile underlying organs and tissues.

In addition to this protective role, the skin also plays major roles in the homeostasis of the entire body. Crucially, the skin’s barrier function helps to keep the body appropriately hydrated by preventing both the rapid loss of water through evaporation and excessive uptake of water when the skin is wet.⁵,⁶ Maintenance of appropriate body temperature is also tightly regulated through the skin.⁷,⁸ By adjusting blood flow and sweat production in the skin, changes in temperature can be corrected rapidly and effectively. In addition to what may be considered the essential protective and homeostatic roles, the skin is the interface that allows us to experience the external environment. As such, the skin has highly developed nerve endings and sensory receptors, allowing us to experience sensations of heat, cold, touch, pressure, and pain. Such mechanoreception is highly functional and acute in the skin, largely as a result of the relatively high density of these sensory receptors.

As well as being the interface with our environment, the skin is also our preliminary interface with each other. The effect of the aesthetic appearance of the skin and the role skin plays in forms of non-verbal communication (e.g. changes in skin colour and texture) are important but sometimes overlooked functions of the skin and should not be underestimated. Skin is a major component of our external appearance and as social beings it plays an important role in the way we interact.

Being responsible for such essential roles including barrier integrity and homeostasis, the skin must be capable of quick and effective repair following injury. Typically, most acute skin injuries heal rapidly, restoring the body’s barrier to the external environment. However, other functional aspects of the skin, including elasticity, strength, sensation, and appearance, are often less well restored.

This chapter outlines the anatomy and physiology of normal healthy skin, the process of wound repair following injury, and the complex regulation of healing in skin.

ANATOMY AND PHYSIOLOGY OF NORMAL SKIN

The basic anatomy of the skin can be divided into two gross components: the outermost layer called the epidermis, and the underlying dermis. However, the skin is much more complex than this.

Continuous with the epidermis are numerous epidermal appendages, including hair follicles, nails, sebaceous glands, and sweat glands, some of which project deep into the dermal layer of the skin. This higher complexity of the skin that includes these additional appendages is often referred to as the integumentary system. Particularly in the setting of wound management, skin is even more complex. Throughout the dermal layer is an extensive and elaborate network of nerves and blood vessels, both intricately linked to the physiology of normal healthy skin. The skin is also host to a plethora of assorted cells from the immune system, including Langerhans cells, T-lymphocytes, mast cells, dermal dendritic cells and granulocytes, and as a frontline of defence against infection, the skin is by necessity an important player in the body’s immunological strategy.

Epidermis

The outermost layer of the skin is called the epidermis (Figure 1.1). This ectodermally derived tissue is the barrier to the external environment that protects the body against microbial, chemical, and physical attack, as well as from damaging UV radiation. The epidermis overwhelmingly comprises cells known as keratinocytes, which are responsible for the structure and barrier formation of the skin. The epidermis is continually self-renewing, with a population of keratinocytes in the innermost layer perpetually dividing and migrating outwards to replace the cells above, which are sloughed from the surface of the skin in a process known as desquamation. This process is tightly regulated in normal skin, with new cells being produced at a rate equal to cell loss. The epidermis itself comprises several layers of keratinocytes at various stages of differentiation. Starting at the innermost layer and moving outwards, the layers of the epidermis are the stratum basale, stratum granulosum, stratum spinosum, and stratum corneum.

Figure 1.1.   Structure of the epidermis. Histological section of human skin depicting the various layers of the epidermis. Cells in the basal layer are attached to the underlying basement membrane, which separates the epidermis from the dermis. Basal cells are mitotically active, but lose their proliferative potential once they detach from the basement membrane and move into the suprabasal layers. As cells move outwards into the spinous layer, they begin to differentiate, altering their cytoskeletal and intercellular connections. As the cells enter the granular layer, they produce and store additional components that contribute to the epidermal barrier. The final stages in the terminal differentiation of epidermal keratinocytes include nuclear degradation, extensive cross-linking of the cornified envelope proteins, and extrusion of the lipid bilayers, helping to form a hydrophobic barrier. The terminal differentiation results in dead, enucleated, flattened squames at the skin surface. These layers of dead cells make up the stratum corneum, and eventually slough from the skin surface as the inner layers of cells continue to replenish them. (AJ Cowin)

Stratum basale (basal layer)

The stratum basale is the innermost layer of the epidermis. This single layer of undifferentiated keratinocytes is at the core of skin’s remarkable self-renewing capacity.⁹ Within the basal layer reside the epidermal stem cells, responsible for the continual division of cells and the replenishment of the epidermis above that occurs throughout an individual’s entire lifespan. Basal cells are maintained as undifferentiated progenitors that can be activated rapidly to proliferate and replenish damaged skin.

Basal cells are typically columnar in appearance and are tightly bound to the underlying basement membrane by electron-dense structures known as hemidesmosomes (HD). Mitotic cellular division in the basal layer typically results in one of the daughter cells remaining attached to the basement membrane in the stratum basale and the other entering the next layer of the epidermis, the stratum spinosum. It is believed that basal cell detachment from the basement membrane induces the expression of genes required for formation of the layers forming the upper barrier.¹⁰,¹¹

In addition to keratinocytes, the stratum basale contains melanocytes, which are responsible for the production and distribution of melanin in the skin.¹² These pigments are the primary determinant of skin colour and confer a level of UV protection.

Stratum spinosum (spinous layer)

The stratum spinosum lies immediately above the stratum basale and consists of several layers of cells that appear more polyhedral than their columnar progenitors. Cells leaving the stratum basale differentiate into suprabasal cells which cease proliferation, downregulate associated cytoskeletal proteins such as keratin 14, upregulate other cytoskeletal proteins such as keratin 10 and increase their cell–cell adhesions.¹³ These are the initial stages of keratinocyte differentiation that will ultimately result in the terminally differentiated keratinocytes found in the stratum corneum. Keratins 1 and 10, the most abundant structural keratins found in the skin, are first produced in this layer. In the uppermost cells of the stratum spinosum, lamellar granules first start to appear.

Stratum granulosum (granular layer)

The stratum granulosum differentiates above the spinous layer. It takes its name from its reserves of granules containing structural proteins such as trichohyalin.¹⁴ These flattened cells lie parallel to the basement membrane, where they continue to differentiate and begin to express and process additional components, including loracrin and filaggrin, that are involved in the maturation of the epidermal cells into the highly organised layers of the stratum corneum.¹⁵,¹⁶ At this stage cells begin the critical process of pyknosis or nuclear degradation that ends with their becoming the cornified layer.¹⁷ Lipids contained within lamellar bodies are exocytosed as the cells move into the stratum corneum, helping to form the hydrophobic barrier of the outer layers of the epidermis. The highly adhesive nature of the epidermal layer creates the protective barrier function of the skin.¹⁸

Stratum corneum

The cells of the stratum corneum are large, very flat, enucleated keratinocytes that have undergone terminal differentiation to form a stratified layer of cells. The cells of the stratum corneum contain keratins and other structural proteins which have been intensely cross-linked to form a rigid and relatively impermeable protective layer. Between the tightly cross-linked cells, specialised lipids help to create a hydrophobic barrier to prevent water and water-soluble compounds from passing through the skin. Although typically thought of as a ‘dead’ layer of skin, evidence suggests that the stratum corneum is metabolically active, capable of processing biomolecules and responding to external stimuli.¹⁹ The cornified layer is continually sloughed off and replaced from below, and through this renewable, layered system the skin is maintained throughout life.

Basement membrane

Located at the epidermal–dermal junction is the basement membrane (BM) (Figure 1.2). The primary function of the BM is to partition the epidermis from the dermis while securing a tight junction between the two cell layers. The BM is composed entirely of extracellular matrix molecules that are produced and secreted from cells in both the basal layer of the epidermis and dermal fibroblasts. The complex mixtures of extracellular matrix molecules including laminin, collagen, fibronectin, tenascin, heparin sulfate proteoglycans and more, form an organised superstructure which allows cells on both sides of the membrane to attach via adhesion proteins and complexes such as hemidesmosomes (HDs). HDs are specialised multiprotein complexes that provide stable adhesion of basal epithelial cells to the BM.²⁰ The importance of HDs in maintaining epithelial integrity is illustrated by two lines of evidence. First, ablation of the genes encoding HD components integrins α6, β4, or plectin in mice results in severe blistering of the skin, causing neonatal death because of an epithelial barrier defect; however, knockout mice lacking structural components of hemidesmosomes, which are targets of auto-antibodies in the blistering condition bullous pemphigoid (BP180 or BP230) display only a mild form of skin blistering.²¹,²²,²³ Second, human patients carrying mutations in any of the HD components suffer from a skin-blistering disorder known as epidermolysis bullosa. The severity of the disease depends on the type and location of the mutations and their consequences at the mRNA and protein levels.²⁴,²⁵

Figure 1.2.   Electron micrograph of murine skin showing the basement membrane zone (BMZ), hemidesmosomes (HD), collagen VII anchoring filaments (AF), and keratin tonofilaments (KT). (EM courtesy of Zlatko Kopecki, UniSA Adelaide).

Dermis

The dermis lies beneath the epidermis and BM and provides the skin with most of its volume, strength, plasticity, and elasticity, as well as secreting most of the nutrients required by the avascular epidermis.

Undulations in the epidermal–dermal interface are known as rete ridges. Finger-like dermal projections known as dermal papillae, rich with blood vessels and neural components, occur at these ridges. The ripples at the epidermal–dermal junction greatly increase the surface area with which the dermis and epidermis can signal to each other, as well as permitting a degree of elasticity, allowing the relatively inflexible epidermis to stretch easily over the more elastic dermis.

The superficial dermal region of adult human skin supports the epidermis during homeostasis, inflammation, and wound repair. It consists of the papillary dermis and the associated rete subpapillare vascular plexus, and is structurally and functionally distinct from the deeper regions of the dermis, known as the reticular dermis. The papillary dermis also contains a higher density of cells and an extracellular matrix that is structurally and compositionally distinct from the reticular dermis.²⁶,²⁷,²⁸

The dermis consists primarily of mesenchymally derived fibroblast cells within a matrix of fibrous extracellular macromolecules that make up the bulk of the dermis. The dermis contains additional cell types, including various immune cells derived from bone marrow, as well as intricate networks of blood vessels and nerves. In addition to supplying nutrients to the avascular epidermis, this vascular network also provides a pathway for the ingress and egress of leucocytes into the adjoining connective tissue.

Fibroblasts

The dermis of adult human skin contains a physiologically heterogeneous population of fibroblasts that interact to produce its unique architecture and that participate in inflammatory and wound repair functions in vivo.²⁸ The fibroblasts that populate the papillary dermis have been shown to be morphologically and physiologically distinct from fibroblasts located in the deep portions of the reticular dermis.²⁹,³⁰ Studies indicate that the dermis contains additional subpopulations located in the intermediate zones of the dermis,³¹ but the extent of fibroblast heterogeneity in the adult dermis is not fully understood.

Papillary dermal fibroblasts cultured in vitro divide faster than site-matched reticular fibroblasts.³⁰ However, reticular fibroblasts display faster contraction of type I collagen lattices than papillary fibroblasts in vitro.³² Papillary and reticular dermis also vary in the type and composition of extracellular matrix (ECM) they produce. Papillary ECM is thin and poorly organised in comparison with the thick, organised bundles of ECM fibres in the reticular dermis. Several components of the ECM, including proteoglycans (decorin and versican), glycoproteins (tenascin-X), and proteins (collagen types III, IV, XII and XVI), are differentially expressed between the papillary and reticular dermis.²⁸ The various disparities between the papillary and reticular dermis undoubtedly reflect a divergence of function between the two dermal layers.

A specialised population of mesenchymal cells that participate in wound repair have been termed myofibroblasts because of their expression of α-smooth muscle actin filaments.³³,³⁴ Human myofibroblasts isolated from wounds have been shown to contract collagen gels faster than do typical fibroblasts.³⁵

There are at least two other types of fibroblasts: the cells of the dermal papilla and dermal sheath that are associated with hair follicles in the skin. In normal skin, dermal sheath cells express α-smooth actin and form a sheath surrounding hair follicles.³⁶ These specialised fibroblasts are intricately coupled to hair follicles and are involved in the complex and highly regulated epithelial–mesenchymal signalling that occurs throughout the development of the hair follicle and the subsequent hair cycles.³⁷,³⁸ They may also play a role in dermal wound healing.³⁹

Subcutaneous tissue

Beneath the dermis lies the subcutaneous tissue or hypodermis, predominantly comprised of vascularised adipose tissue. Although not strictly part of the skin, this subcutaneous fat provides the body with energy reserves, thermal insulation, and a further degree of protection from physical trauma.

SKIN APPENDAGES

Cutaneous appendages found in the skin include sweat glands, sebaceous glands, hair follicles, and nails. These skin appendages are primarily derived from the epithelium, but hair and nails in particular have indispensable dermal components in close association. The highly regulated reciprocal signalling of epithelial and mesenchymal components of these appendages is essential for their development and maintenance in the skin.

Figure 1.3   Depiction of a mature hair follicle. The hair matrix consists of proliferating cells encasing the dermal papilla. Upon differentiation, matrix cells produce the concentric rings of cells that generate the hair shaft and inner root sheath. The outer root sheath is continuous with the basal layer of the epidermis. The companion layer separates the outer root sheath from the inner. The outer root sheath contains follicular stem cells nested in the bulge niche underneath the sebaceous gland. The upper matrix contains melanocytes. The hair follicle is surrounded by a sheath of connective tissue cells known as the dermal sheath. In contrast to the hair follicle permanent segment, the cycling lower segment undergoes phases of growth and degeneration.

Each of these skin appendages plays an important role in the homeostasis of the skin and the entire body. The sweat glands contribute to thermoregulation of the body by producing sweat, which is evaporated from the surface of the skin, cooling the tissue and its blood supply, and the cooled blood is then circulated throughout the rest of the body. Sebaceous glands are commonly associated with hair follicles, but are also present in non-hairy skin, with the exception of the palms and the soles of feet. They secrete an oily substance called sebum that coats and lubricates the hair and skin, protecting it from excessive drying and irritation. Hair follicles are large skin appendages that extend deep into the dermis and, during some stages of their growth cycle, into the hypodermis (Figure 1.3). Hair provides us with numerous benefits, including heat retention, dispersion of sweat and sebum, and sensory perception at a level above the skin; hair also has sociologically important functions.⁴⁰ Hair follicles are a reservoir of epithelial stem cells with great proliferative potential.⁴¹,⁴² Hair follicle cells are also important contributors during wound healing, with epithelial stem cells migrating out of nearby hair follicles to contribute to the newly formed epidermis,⁴³,⁴⁴ although the persistence of these hair follicle cells in the healed wound is limited.⁴⁵ Dermal papilla cells associated with hair follicles may also contribute to dermal wound healing.³⁹ Nails, which are structurally and compositionally closely related to hair follicles, cover the extremities of the fingers and toes, providing physical protection and rigidity to a particularly vulnerable region of skin.

VASCULATURE AND NERVOUS SYSTEMS OF THE SKIN

The dermis is well vascularised to provide oxygen and nutrients to the dermal cells and, by diffusion through the BM, to the lower levels of the avascular epidermis. However, the density of blood vessels in the dermis is beyond what is required for the provision of nutrients. The body is able to regulate its temperature, with assistance from sweat glands, by altering the flow of blood to the surface of the body by constriction or dilation of the vessels in the skin. Dilated vessels allow more blood to flow into the skin where it is cooled before circulating back to the heart and through the rest of the body, while constricted vessels keep blood away from the skin and in the warmer core of the body.

The skin is also innervated with a complex network of nerves, comprising a variety of types, both sensory and autonomic, linking the skin to the central nervous system and allowing a level of neuronal influence over the physiology and pathology of skin.⁴⁶ The nerves in the skin are predominantly sensory, with a minority of dermisrestricted autonomic nerves involved in regulating blood circulation, lymphatic function, and skin appendages. Sensory nerves are responsible for detecting mechanical and thermal inputs and relaying those messages to the central nervous system (CNS), which interprets the signals as heat, cold, touch, pressure, or pain.⁴⁷ In addition, evidence suggests that the cutaneous nervous system is also intricately involved during wound repair, influencing processes like inflammation, cell proliferation, cytokine production, and revascularisation.⁴⁸

IMMUNE CELLS IN THE SKIN

As an important frontline defence in protecting the body from microbial attack, the skin is home to a variety of bone-marrow-derived immune cells that are capable of eliciting both innate and adaptive immune responses. Epidermally located Langerhans cells, as well as dermal mast cells (MC), dendritic cells (DC), and macrophages, are all present in normal skin. The role of MC in innate immune responses of the skin has largely been neglected; however, their particular pattern of distribution in the skin, and their ability to sense and react to pathogens and other danger signals, indicate that MC can be important sentinels and effector cells in skin immune responses.⁴⁹ Upon activation, these cells are capable of releasing various molecules to elicit a rapid but relatively nonspecific innate immune response, fending off potential pathogens as well as recruiting additional immune cells from the circulating blood (Figure 1.4). Langerhans cells in the epidermis and dermal dendritic cells are also capable of taking up, processing and presenting antigens that penetrate the skin to T-cells after migration to the lymph nodes. These antigen-presenting cells are capable of activating the adaptive immune response and memory T-cells to elicit a systemic immune response.

Figure 1.4.   Skin mast cells sense and react to various danger signals. TLR = toll-like receptor; ET = endothelin; CRH = corticotropin releasing hormone; LN = lymph node. Reprinted from Metz and Maurer⁴⁹, copyright 2007, with permission from Elsevier.

CLASSIC STAGES OF WOUND REPAIR

When the skin is damaged, the body undergoes a carefully orchestrated process of wound repair. The numerous types of acute cutaneous wounds include incisional wounds, excisional wounds, burns, scalds, and chemical injuries. Despite the variety of wound types, the wound-healing process is relatively conserved for most types of cutaneous injuries.⁴ Described below and shown in Figure 1.5 are the steps involved in typical, non-pathogenic wound healing. These include the production of a fibrin clot, inflammation, re-epithelialisation, dermal repair, and tissue remodelling. The coordination of these processes requires multicellular and temporally dynamic control mechanisms. These are complex and difficult to elucidate: although the stages of wound healing are outlined sequentially below, in reality they overlap and influence each other throughout the wound-healing process.

Production of the fibrin clot

Injury to the skin will almost inevitably result in damage to blood vessels. Haemostasis is achieved initially by the formation of a platelet plug, followed by fibrin matrix, which becomes the scaffold for infiltrating cells and rapid restoration of a temporary barrier to the external environment (Figure 1.5a).⁵⁰,⁵¹ Essential to the clotting process is the activation, adhesion, and aggregation of platelets.⁵² Activated platelets release a cocktail of cytokines, extracellular matrix, and adhesive proteins that help to form the dense provisional matrix of the clot. Many of these platelet-derived factors lead to further clotting and platelet aggregation, as well as chemotactic and growth signals that promote an influx of immune cells from the blood, migration and proliferation in the surrounding epidermis and connective tissue, and neovascularisation of the wound.

Inflammation

Usually within minutes of injury, neutrophils and monocytes are recruited from the circulating blood to the wound in response to the activation of complement, the degranulation of platelets and the products of bacterial degradation (Figure 1.5a).⁵³

Once in the skin, neutrophils are primarily concerned with the clearance and destruction of contaminating bacteria. This is usually achieved in phagolysosomes, but often results in neutrophils attacking their surroundings with free radicals that kill many otherwise-healthy host cells as well as the target infectious agents. This is particularly apparent in chronic wounds, and might well underlie the persistent tissue-destroying nature of such wounds.⁵⁴ New studies have shown that another tactic for killing by neutrophils involves trapping microbes in extruded nets of histones and DNA.⁵⁵ Unless bacterial contamination persists, the neutrophils will cease their influx after a few days. The majority of neutrophils will be confined within the clot and be sloughed from the skin as the wound is repaired beneath them. Any neutrophils remaining in the skin will senesce before eventually being phagocytosed themselves by macrophages.

Monocytes, which initially enter into the wound site at the same time as the neutrophils, continue to accumulate after neutrophil recruitment has ceased. Once at their intended location, monocytes mature into tissue macrophages capable of the phagocytosis and digestion of lingering pathogenic organisms and cellular and extracellular debris, including fibrin and spent neutrophils.⁵⁶ Macrophages also produce numerous cytokines and growth and angiogenic factors that are believed to play important roles in the regulation of fibro-proliferation and angiogenesis.⁵⁷,⁵⁸ These overlapping cocktails of growth factors and cytokines are presumed to function as tissue repair signals, directing the various behaviours of the host cells as they draw the wound closed, but they also act to amplify the inflammatory signal, so drawing in yet more neutrophils, macrophages, and MC. However, recent data suggest that a deficiency in either neutrophils or macrophages can be compensated for by the redundancy in the inflammatory response.⁵⁴ The repair of small wounds can still occur in the absence of both cell types, and the scarring response is even less.⁵⁹ Only when infection has been countered and repair completed will these inflammatory cells disperse from the wound site.

Re-epithelialisation

Re-epithelisation involves migration and proliferation of keratinocytes to cover the denuded dermal surface.⁶⁰ It is a crucial step during wound healing, and proceeds by a sequence of basal and suprabasal epithelial cell activation at the wound edge, migration of these activated keratinocytes into the wound, proliferation of keratinocytes in the wake of the migration front, and finally, once the wound is closed, differentiation into a mature epidermal barrier. Migrating keratinocytes undergo subcellular modifications including: disassembly of HD links between epidermis and BM; retraction of intracellular tonofilaments and keratin filaments; dissolution of most desmosomes; and formation of peripheral cytoplasmic actin filaments (lamellipodia) and focal contacts.⁶¹,⁶²

As epidermal migration moves on, keratinocytes at the wound margin begin to proliferate behind the actively migrating cells. The resulting dense hyperproliferative epithelium feeds the migrating sheets at the wound margins.⁶² Activation of integrin receptors by migrating keratinocytes allows the interaction with a variety of ECM proteins interspersed in the provisional wound bed and at the wound margin. Moreover, expression and activation of matrix metalloproteinases (MMPs) promotes degradation and modification of ECM proteins at the wound site, facilitating cell migration.⁶³ Then, BM proteins reappear in a very ordered sequence from the margin of the wound inward, in a zipper-like fashion. Epidermal cells revert to their normal phenotype, once again firmly attached to the reestablished BM and underlying dermis. Once the wound has been covered, basal keratinocytes stop migrating, re-form their strong attachments to the newly formed BM, and revert to a normal program of division. Suprabasal cells that were activated during wound repair return to their typical state and continue a standard differentiation program to re-establish the stratified, cornified barrier to the external environment.

Figure 1.5.   Classic stages of wound repair. There are three classic stages of wound repair: inflammation, new tissue formation, and remodelling. (a) Inflammation. This stage lasts until about 48 h after injury. Depicted is a skin wound at about 24–48 h after injury. The wound is characterised by a hypoxic (ischaemic) environment in which a fibrin clot has formed. Bacteria, neutrophils, and platelets are abundant in the wound. Normal skin appendages (such as hair follicles and sweat duct glands) are still present in the skin outside the wound. (b) New tissue formation. This stage occurs about 2–10 days after injury. Depicted is a skin wound at about 5–10 days after injury. An eschar (scab) has formed on