Advanced Textiles for Wound Care

Woodhead Publishing in Textiles: Number 85

Advanced textiles for wound care Edited by S. Rajendran

Oxford

© 2009 Woodhead Publishing Limited

Cambridge

New Delhi

The Textile Institute and Woodhead Publishing The Textile Institute is a unique organisation in textiles, clothing and footwear. Incorporated in England by a Royal Charter granted in 1925, the Institute has individual and corporate members in over 90 countries. The aim of the Institute is to facilitate learning, recognise achievement, reward excellence and disseminate information within the global textiles, clothing and footwear industries. Historically, The Textile Institute has published books of interest to its members and the textile industry. To maintain this policy, the Institute has entered into partnership with Woodhead Publishing Limited to ensure that Institute members and the textile industry continue to have access to high calibre titles on textile science and technology. Most Woodhead titles on textiles are now published in collaboration with The Textile Institute. Through this arrangement, the Institute provides an Editorial Board which advises Woodhead on appropriate titles for future publication and suggests possible editors and authors for these books. Each book published under this arrangement carries the Institute’s logo. Woodhead books published in collaboration with The Textile Institute are offered to Textile Institute members at a substantial discount. These books, together with those published by The Textile Institute that are still in print, are offered on the Woodhead web site at: www.woodheadpublishing.com. Textile Institute books still in print are also available directly from the Institute’s website at: www.textileinstitutebooks.com. A list of Woodhead books on textile science and technology, most of which have been published in collaboration with The Textile Institute, can be found at the end of the contents pages.

© 2009 Woodhead Publishing Limited

Published by Woodhead Publishing Limited in association with The Textile Institute Woodhead Publishing Limited, Abington Hall, Granta Park, Great Abington Cambridge CB21 6AH, UK www.woodheadpublishing.com Woodhead Publishing India Private Limited, G-2, Vardaan House, 7/28 Ansari Road, Daryaganj, New Delhi – 110002, India Published in North America by CRC Press LLC, 6000 Broken Sound Parkway, NW, Suite 300, Boca Raton, FL 33487, USA First published 2009, Woodhead Publishing Limited and CRC Press LLC © Woodhead Publishing Limited, 2009 The authors have asserted their moral rights. This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. Reasonable efforts have been made to publish reliable data and information, but the authors and the publishers cannot assume responsibility for the validity of all materials. Neither the authors nor the publishers, nor anyone else associated with this publication, shall be liable for any loss, damage or liability directly or indirectly caused or alleged to be caused by this book. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfi lming and recording, or by any information storage or retrieval system, without permission in writing from Woodhead Publishing Limited. The consent of Woodhead Publishing Limited does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific permission must be obtained in writing from Woodhead Publishing Limited for such copying. Trademark notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe. British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library. Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress. Woodhead Publishing ISBN 978-1-84569-271-1 (book) Woodhead Publishing ISBN 978-1-84569-630-6 (e-book) CRC Press ISBN 978-1-4200-9489-3 CRC Press order number WP9489 The publishers’ policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp which is processed using acid-free and elemental chlorine-free practices. Furthermore, the publishers ensure that the text paper and cover board used have met acceptable environmental accreditation standards. Typeset by SNP Best-set Typesetter Ltd., Hong Kong Printed by TJ International Limited, Padstow, Cornwall, UK

© 2009 Woodhead Publishing Limited

Contents

Contributor contact details Woodhead Publishing in Textiles Preface

Part I The use of textiles in particular aspects of wound care 1 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2

2.1 2.2 2.3 2.4 2.5 2.6 2.7

xi xv xxi

1

Wound management and dressings S. Ather and K. G. Harding, Cardiff University, UK

3

Introduction Types of wound Mechanism of wound healing Factors affecting wound healing: why wounds fail to heal Wound healing: treatment options Future trends Conclusions References

3 3 4

Testing dressings and wound management materials S. T. Thomas, formerly of Surgical Materials Testing Laboratory, Medetec, UK Introduction The need for laboratory testing Fluid-handling tests Low-adherence tests Conformability tests Microbiological tests Odour control tests

11 13 17 18 18

20

20 21 23 36 37 38 42 v

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Contents

2.8 2.9

Biological tests References

3

3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 3.10 3.11 3.12 4

4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 5 5.1 5.2 5.3 5.4

Textile materials and structures for wound care products B. S. Gupta, North Carolina State University, USA, and J. V. Edwards, United States Department of Agriculture – Agricultural Research Service, USA Introduction The role of wound dressings Categorization of wounds Minor wounds Healing mechanisms Wound dressings Types of dressings available Bandages Materials used in dressings and bandages Textile processes involved in formation of dressings and bandages Acknowledgement References Interactive dressings and their role in moist wound management C. Weller, Monash University, Australia

44 45

48

48 49 50 51 53 55 60 70 71 79 92 92

97

Introduction Normal wound healing Wound characteristics Dressings Interactive wound dressings Future trends Conclusions Sources of further information and advice References

97 98 100 102 105 110 111 112 112

Bioactive dressings to promote wound healing G. Schoukens, Ghent University, Belgium

114

Introduction Physiology of wound healing Principles and roles of bioactive dressings Types and structures of bioactive dressings

114 115 117 118

© 2009 Woodhead Publishing Limited

Contents 5.5 5.6 5.7 5.8 6

Example of bioactive dressing: di-O-butyrylchitin (DBC) Future trends Acknowledgements References

vii

127 144 146 146

Advanced textiles for wound compression S. Rajendran and S. C. Anand, University of Bolton, UK

153

6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9

Introduction Elastic compression bandages Venous leg ulcers Venous leg ulcer treatment Applications of bandages Present problems and novel bandages Three-dimensional spacer compression bandages Conclusions References

153 154 155 157 163 165 169 175 175

7

Antimicrobial textile dressings in managing wound infection Y. Qin, Jiaxing College, China

179

7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 8

8.1 8.2 8.3 8.4

Introduction Topical antimicrobial agents in wound care Main types of antimicrobial wound dressings Wound dressings containing silver Applications of modern antimicrobial wound dressings containing silver Future trends Sources of further information and advice References Novel textiles in managing burns and other chronic wounds H. Onishi and Y. Machida, Hoshi University, Japan Introduction: current practice in the management of deep skin wounds or ulcers Normal treatment options for deep skin wounds or ulcers Novel wound dressings for managing deep skin wounds or ulcers Future trends

© 2009 Woodhead Publishing Limited

179 181 183 187 190 193 195 195

198

198 201 205 212

viii

Contents

8.5 8.6

Sources of further information and advice References

Part II Types of advanced textiles for wound care 9

215 215

221

Drug delivery dressings P. K. Sehgal, R. Sripriya and M. Senthilkumar, Central Leather Research Institute, India

223

9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 9.9

Introduction Wounds: defi nition and types Wounds which require drug delivery Delivering drugs to wounds Types of dressings for drug delivery Applications of drug delivery dressings Future trends Conclusions References

223 224 226 231 235 240 244 246 247

10

The use of ‘smart’ textiles for wound care J. F. Kennedy and K. Bunko, Advanced Science and Technology Institute, UK

254

10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.8 10.9

Introduction Basic principles and types of smart textiles Characteristics of smart textiles Textiles in control of exudate from wounds Examples of ‘smart’ textiles for wound care Response of dressings to bacteria Future trends Sources of further information and advice References

254 255 256 262 265 267 268 271 272

11

Composite dressings for wound care M. Joshi and R. Purwar, Indian Institute of Technology Delhi, India

275

11.1 11.2 11.3 11.4

Introduction Defi nition of composite dressings Structure of composite dressings Materials and textile structures used in composite dressings

275 276 277

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Contents

ix

11.5 11.6 11.7 11.8

Types of composite dressings Trends in composite dressings: embroidery technology Conclusions References

284 286 288 288

12

Textile-based scaffolds for tissue engineering M. Kun, C. Chan and S. Ramakrishna, National University of Singapore, Singapore

289

12.1 12.2 12.3 12.4

Introduction: principles of tissue engineering Properties required for fibrous scaffolds Materials used for scaffolds Relationship between textile architecture and cell behavior Textiles used for tissue scaffolds and scaffold fabrication Applications of textile scaffolds in tissue engineering Future trends Sources of further information and advice References

289 290 293

12.5 12.6 12.7 12.8 12.9

© 2009 Woodhead Publishing Limited

294 298 303 308 310 312

Contributor contact details

(* = main contact)

Chapter 3

Chapter 1

Professor Bhupender S Gupta* Department of Textile Engineering, Chemistry & Science College of Textiles North Carolina State University Raleigh, NC 27695-8301 USA

Shahzad Ather and Keith G Harding* Wound Healing Research Unit Department of Surgery Cardiff University Cardiff UK E-mail: [email protected]

Chapter 2 Dr Stephen Thomas MEDETEC 1 Radyr Farm Road Radyr Cardiff CF15 8EH UK

E-mail: [email protected] Dr J Vincent Edwards USDA-ARS Southern Regional Research Center 1100 Robert E Lee Blvd New Orleans LA 70124 USA E-mail: [email protected]. gov

E-mail: [email protected] [email protected]

xi

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xii

Contributor contact details

Chapter 4

Chapter 7

Carolina Weller Department of Epidemiology and Preventative Medicine School of Public Health and Preventative Medicine Monash University Level 3 Burnet Building, DEPM The Alfred 89 Commercial Road Melbourne Vic 3004 Australia

Dr Yimin Qin Biochemical Materials Research and Development Center Jiaxing College 56 Yuexiu Road South Jiaxing 314001 Zhejiang Province China

E-mail: Carolina.Weller@med. monash.edu.au

Chapter 5 Professor Gustaaf Schoukens Ghent University Faculty of Engineering Sciences Department of Textiles Technologiepark 907 B-9052 Zwijnaarde (Gent) Belgium E-mail: gustaaf.schoukens@ UGent.be

Chapter 6 Dr S Rajendran* and S C Anand Centre for Materials Research and Innovation University of Bolton Bolton BL3 5AB UK E-mail: [email protected]

© 2009 Woodhead Publishing Limited

E-mail: [email protected]

Chapter 8 Hiraku Onishi* and Yoshiharu Machida Department of Drug Delivery Research Hoshi University 2-4-41, Ebara Shinagawa-ku Tokyo 142-8501 Japan E-mail: [email protected]

Chapter 9 Dr P K Sehgal*, Dr R Sripriya and Dr M Senthilkumar Bioproducts Laboratory Central Leather Research Institute Adyar, Chennai 600 020 Tamil Nadu India E-mail: [email protected]

Contributor contact details

xiii

Chapter 10

Chapter 11

John F Kennedy* and Katarzyna Bunko Advanced Science and Technology Institute 5 The Croft, Buntsford Drive Stoke Heath, Bromsgrove Worcestershire B60 4JE UK

M Joshi* and Roli Purwar Department of Textile Technology Indian Institute of Technology Delhi New Delhi 110016 India

E-mail: [email protected]

Chapter 12

Formerly of Chembiotech Laboratory University of Birmingham Research Park Vincent Drive Birmingham B15 2SQ UK

E-mail: [email protected] [email protected]

Ma Kun, Casey K. Chan and Seeram Ramakrishna* Division of Bioengineering & Dept. of Mechanical Engineering, Faculty of Engineering National University of Singapore Singapore 119077 E-mail: [email protected]

© 2009 Woodhead Publishing Limited

Woodhead Publishing in Textiles

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Watson’s textile design and colour Seventh edition Edited by Z. Grosicki Watson’s advanced textile design Edited by Z. Grosicki Weaving Second edition P. R. Lord and M. H. Mohamed Handbook of textile fi bres Vol 1: Natural fi bres J. Gordon Cook Handbook of textile fi bres Vol 2: Man-made fi bres J. Gordon Cook Recycling textile and plastic waste Edited by A. R. Horrocks New fi bers Second edition T. Hongu and G. O. Phillips Atlas of fi bre fracture and damage to textiles Second edition J. W. S. Hearle, B. Lomas and W. D. Cooke Ecotextile ’98 Edited by A. R. Horrocks Physical testing of textiles B. P. Saville Geometric symmetry in patterns and tilings C. E. Horne Handbook of technical textiles Edited by A. R. Horrocks and S. C. Anand Textiles in automotive engineering W. Fung and J. M. Hardcastle Handbook of textile design J. Wilson High-performance fi bres Edited by J. W. S. Hearle Knitting technology Third edition D. J. Spencer

xv

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xvi 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

Woodhead Publishing in Textiles Medical textiles Edited by S. C. Anand Regenerated cellulose fi bres Edited by C. Woodings Silk, mohair, cashmere and other luxury fi bres Edited by R. R. Franck Smart fi bres, fabrics and clothing Edited by X. M. Tao Yarn texturing technology J. W. S. Hearle, L. Hollick and D. K. Wilson Encyclopedia of textile fi nishing H-K. Rouette Coated and laminated textiles W. Fung Fancy yarns R. H. Gong and R. M. Wright Wool: Science and technology Edited by W. S. Simpson and G. Crawshaw Dictionary of textile fi nishing H-K. Rouette Environmental impact of textiles K. Slater Handbook of yarn production P. R. Lord Textile processing with enzymes Edited by A. Cavaco-Paulo and G. Gübitz The China and Hong Kong denim industry Y. Li, L. Yao and K. W. Yeung The World Trade Organization and international denim trading Y. Li, Y. Shen, L. Yao and E. Newton Chemical fi nishing of textiles W. D. Schindler and P. J. Hauser Clothing appearance and fit J. Fan, W. Yu and L. Hunter Handbook of fi bre rope technology H. A. McKenna, J. W. S. Hearle and N. O’Hear Structure and mechanics of woven fabrics J. Hu Synthetic fi bres: nylon, polyester, acrylic, polyolefi n Edited by J. E. McIntyre Woollen and worsted woven fabric design E. G. Gilligan Analytical electrochemistry in textiles P. Westbroek, G. Priniotakis and P. Kiekens

© 2009 Woodhead Publishing Limited

Woodhead Publishing in Textiles 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Bast and other plant fi bres R. R. Franck Chemical testing of textiles Edited by Q. Fan Design and manufacture of textile composites Edited by A. C. Long Effect of mechanical and physical properties on fabric hand Edited by Hassan M. Behery New millennium fi bers T. Hongu, M. Takigami and G. O. Phillips Textiles for protection Edited by R. A. Scott Textiles in sport Edited by R. Shishoo Wearable electronics and photonics Edited by X. M. Tao Biodegradable and sustainable fi bres Edited by R. S. Blackburn Medical textiles and biomaterials for healthcare Edited by S. C. Anand, M. Miraftab, S. Rajendran and J. F. Kennedy Total colour management in textiles Edited by J. Xin Recycling in textiles Edited by Y. Wang Clothing biosensory engineering Y. Li and A. S. W. Wong Biomechanical engineering of textiles and clothing Edited by Y. Li and D. X-Q. Dai Digital printing of textiles Edited by H. Ujiie Intelligent textiles and clothing Edited by H. Mattila Innovation and technology of women’s intimate apparel W. Yu, J. Fan, S. C. Harlock and S. P. Ng Thermal and moisture transport in fi brous materials Edited by N. Pan and P. Gibson Geosynthetics in civil engineering Edited by R. W. Sarsby Handbook of nonwovens Edited by S. Russell Cotton: Science and technology Edited by S. Gordon and Y-L. Hsieh Ecotextiles Edited by M. Miraftab and A. Horrocks

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xviii 61 62 63 64 65 66 67 68 69 70 71 72 73 74

75 76 77 78 79 80 81

Woodhead Publishing in Textiles Composite forming technologies Edited by A. C. Long Plasma technology for textiles Edited by R. Shishoo Smart textiles for medicine and healthcare Edited by L. Van Langenhove Sizing in clothing Edited by S. Ashdown Shape memory polymers and textiles J. Hu Environmental aspects of textile dyeing Edited by R. Christie Nanofi bers and nanotechnology in textiles Edited by P. Brown and K. Stevens Physical properties of textile fi bres Fourth edition W. E. Morton and J. W. S. Hearle Advances in apparel production Edited by C. Fairhurst Advances in fi re retardant materials Edited by A. R. Horrocks and D. Price Polyesters and polyamides Edited by B. L. Deopora, R. Alagirusamy, M. Joshi and B. S. Gupta Advances in wool technology Edited by N. A. G. Johnson and I. Russell Military textiles Edited by E. Wilusz 3D fi brous assemblies: Properties, applications and modelling of three-dimensional textile structures J. Hu Medical textiles 2007 Edited by J. Kennedy, A. Anand, M. Miraftab and S. Rajendran Fabric testing Edited by J. Hu Biologically inspired textiles Edited by A. Abbott and M. Ellison Friction in textile materials Edited by B. S. Gupta Textile advances in the automotive industry Edited by R. Shishoo Structure and mechanics of textile fi bre assemblies Edited by P. Schwartz Engineering textiles: Integrating the design and manufacture of textile products Edited by Y. E. El-Mogahzy

© 2009 Woodhead Publishing Limited

Woodhead Publishing in Textiles 82 83 84 85 86 87

Polyolefi n fi bres: industrial and medical applications Edited by S. C. O Ugbolue Smart clothes and wearable technology Edited by J. McCann and D. Bryson Identification of textile fi bres Edited by M. Houck Advanced textiles for wound care Edited by S. Rajendran Fatigue failure of textile fi bres Edited by M. Miraftab Advances in carpet technology Edited by K. Goswami

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xix

Preface

It is apparent that quality of life is a key issue in the healthcare of people. Textile materials play an important and crucial role in designing appropriate structures for the healthcare of people and medical companies. With the increasing threat from new strains of bacteria and viruses and the growing problems such as Deep Vein Thrombosis (DVT) and leg ulcers, it is vital that new or enhanced medical devices should be developed to cope with the situation. The market potential for medical textile products is considerable. The UK has one of the largest medical device markets in the world. The market is dominated by the National Health Service (NHS), accounting for approximately 80% of healthcare expenditure. There is a considerable high market potential for advanced wound dressings. The wound care industry generated between US$3.5 and 4.5 billion for the period between 2003 and 2006, mostly from the USA and Europe. The wound care market is predicted to grow to US$12.5 billion in 2012 and the global advanced wound care segment is the fastest growing area with growth of 10% a year. In Europe the advanced wound care market is expected to grow by an average of 12.4% a year to US$1.23 billion in 2010. The growth forecast for antimicrobial wound dressing is 25.9% per annum. In the USA alone there are over 100 000 surgeries performed daily which can result in surgical wounds. Ageing population creates increased demand for all types of surgical intervention. In 1991 the estimated annual cost of treating pressure ulcers in the UK was over £750 million, and in 2004 the total costs were £1.4– £2.1 billion or 4% of the total NHS budget. The annual cost of treating diabetic foot ulceration accounts for 5% of the total NHS budget in the UK. The annual cost for treating venous leg ulceration in Britain is £650 million and in the USA it is around $1 billion. While traditional dressings currently dominate the wound care market, raising awareness of the clinical benefits provided by advanced wound dressings is bound to widen their uptake. Continued research and development into developing high-tech wound dressings that fulfi l the principal xxi

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Preface

essential requirements of keeping the wound moist to accelerate healing, being nonadherent to wound bed and having antibacterial and antiodour properties not only promotes wound healing with special reference to difficult-to-heal wounds but also reduces the treatment cost considerably which, in turn, has a direct impact on the economy. Wound management is a global problem and the need for a comprehensive book which links textiles and wounds for better wound management has been felt for a long time. This interdisciplinary state-of-the art book has been designed to meet the growing challenges in advanced wound care management. The chapters are carefully written by multinational authors who have vast experience in medical and/or textile disciplines. During editing I found that the chapters not only provide a wealth of information on wound management but also problem-solving techniques. The book is organised into two parts. The chapters in Part I address the principles and physiology of wounds and wound healing, and how textiles play a vital role in managing acute and chronic wound healing. Part I emphasises the fact that wound healing depends not only on medication but also on the use of proper dressing techniques and suitable dressing materials. Dressings vary with the type of wound and wound management, and no single dressing is universally applicable in enhancing wound healing. The role of interactive dressings, bioactive dressings, antimicrobial dressings and special dressings for managing burn wounds is critically discussed in Part I. In addition, a chapter in Part I demonstrates that textile bandages are the only treatment option to enhance the healing of difficult-to-heal venous leg ulcers. The testing and characterisation of wound dressings are also critically reviewed taking account of the real laboratory scenario. The high-tech dressings such as drug delivery dressings, temperature control dressings, smart dressings and composite dressings are focused in Part II. A unique last chapter covers the cultivation of human organs and body parts on textile scaffolds. Each chapter includes a wealth of bibliographical information which can serve as a ‘ready reckoner’ for finding additional information in specific subject area. Efforts have been exerted to edit the chapters to be easily readable by medical professionals, textile scientists and researchers as well as wound dressing manufacturers. This book provides readers with much needed information in the interdisciplinary subject areas of nursing and textiles. I am deeply indebted to the authors of this publication and have no doubt that their contribution will be a useful resource document making a greater contribution to this emerging discipline. S. Rajendran The University of Bolton

© 2009 Woodhead Publishing Limited

1 Wound management and dressings S. AT H E R and K. G. H A R DI NG, Cardiff University, UK

Abstract: The various types of wounds and their mechanisms of healing are described and factors affecting the management of wound healing are outlined. For chronic wounds, a number of factors when present in combination lead to the non-healing of wounds. Wound management should therefore be multifactorial and aim at correcting the underlying abnormalities. Options for treatment are described with no single treatment being universally effective owing to the multiple molecular and cellular events involved so that a combination of different therapies is required. Future trends include application of gene therapy and stem cell therapy. Key words: wound healing, wound management, chronic wounds.

1.1

Introduction

A wound is defi ned as a break in the epithelial integrity of the tissues. This disruption can be deeper and involve subepithelial tissues including dermis, fascia and muscle. They can be caused accidentally, intentionally or be a part of a disease process.1 A wound is caused by physical trauma where the skin is torn, cut or punctured (an open wound), or where a blunt force trauma causes a contusion (a closed wound). The history of wound care spans from prehistory to modern medicine and has evolved from simple wound covers ranging from vinegar-soaked dressings, through topical antibiotics to topically applied growth factors. 2 Even during early historical periods several factors were noted that speeded up or assisted the process of healing. The necessity for hygiene, the prevention of bleeding and, later on, the germ theory of disease paved the way for modern wound management.

1.2

Types of wound

Wounds can be classified in many ways, by acute or chronic, by cause (e.g., pressure, trauma, venous leg ulcer, diabetic foot ulcer), by the depth of tissue involvement, or other characteristics such as closure (primary or secondary intention). 3

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Advanced textiles for wound care

1.2.1 Acute wound An acute wound is defi ned as a recent wound that has yet to progress through the sequential stages of wound healing. 3 An acute wound is acquired as a result of an incision or trauma and heals in a timely and orderly manner. Surgically created wounds include all incisions, excisions, and wounds that are surgically debrided. Surgical wounds include all skin lesions that occur as a result of trauma (e.g. burns, falls), as a result of an underlying condition (e.g. leg ulcers), or as a combination of both.

1.2.2 Chronic wounds Wounds that fail to heal in an anticipated time frame and orderly fashion and often recur are considered chronic. 3 Venous leg ulcers, pressure ulcers and diabetic foot ulcers are some examples of chronic wounds.

1.2.3 Open and closed wounds Wounds are also differentiated as open or closed wound types: Open wounds: examples include incision or incised wounds, laceration, abrasions, punctured wounds and penetrating wounds, Closed wounds: examples include contusions, haematoma and crush injuries.

1.3

Mechanism of wound healing

The aim of wound healing is homeostasis and restoration of tissue integrity. It is a well-orchestrated and complex process which is triggered by tissue injury and ends by regeneration or repair. Typically healing is divided into categories based on the anticipated nature of the repair process (Fig. 1.1).

1.3.1 Healing by primary intention Wound edges are approximated with sutures, staples or adhesive within hours of its creation with no defect. This enables closure to occur quickly with minimal tissue needed to repair the defect and minimal scarring.

1.3.2 Healing by secondary intention The wound is left open and no formal closure is done. Healing occurs by epithelialisation and contraction, e.g. healing associated with a large and/or deep wound in which the tissue edges cannot be approximated. The

© 2009 Woodhead Publishing Limited

Wound management and dressings

5

Differential wound healing Wound healing

Scarless Foetal skin, oral mucosa

Scarring Adult skin

Non-healing Chronic wounds

Excessive scarring Hypertrophic scars, keloid scars

1.1 Differential wound healing.

size of the gap determines the degree of new tissue matrix and epidermal surface needed for complete closure.4

1.3.3 Delayed primary/tertiary healing Wound closure is delayed for several days; this is usually employed for infected wounds. Irrespective of the cause, wounds heal in a very similar fashion. Studying this process and how to optimise this remains the central focus of attention for the clinicians. It is a dynamic and interactive process that involves a variety of blood and parenchymal cells, extracellular matrices and soluble mediators. During this process, wound healing passes through four phases of haemostasis, inflammation, proliferation and remodelling. These phases are clinically indistinct and overlap in time. Tissue injury sets in motion a cascade of cellular and biochemical activities which leads to healing of the wound. In the following sections, stages in the process of wound healing are described (Fig. 1.2).

1.3.4 Haemostasis The fi rst step in the process (immediate up to 2–4 h) of inflammation is haemostasis, which is characterised by vasoconstriction and coagulation. It starts soon after injury and is usually completed within the first few hours. Injury to the tissues causes disruption of blood vessels and lymphatics exposing the platelets to fibrin and collagen. This activates the

© 2009 Woodhead Publishing Limited

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Advanced textiles for wound care Wound biology Injury

Platelet activation Fibrin clot

Macrophages

Provisional Growth factors matrix Proteases ECM production Re-epithelialisation Migration Granulation tissue

Fibroblast ↓ ↓ ↑ ↑ ↑

Cellular density Blood supply Contraction Collagen orientation Epithelial thickness

Scar formation/ maturation

1.2 Biology of wound healing.

platelets and complement cascade. Platelets also interact with the injured tissue, causing the release of thrombin, which converts soluble, circulating fibrinogen to fibrin, which in turn traps, and activates platelets and forms the physical entity of the hemostatic ‘plug’. 5 The activated platelet releases cytokines and growth factors including thromboxane A-2 and serotonin which are important inflammatory mediators and also cause vasoconstriction The clot also serves to concentrate the elaborated cytokines and growth factors including platelet-derived growth factor (PDGF) and transforming growth factor (TGF) β1.6 Coagulation leads to hemostasis, which initiates healing by leaving behind messengers that bring on an inflammatory process. Deficiency of clotting factors (Factor VII. IX, XII) leads to impaired wound healing.7

1.3.5 Inflammation The stage of inflammation starts soon after haemostasis (immediate up to 2–5 days) and is usually completed within the fi rst 48 to 72 h but it may last as long as 5 to 7 days. 8 The initial vasoconstriction is followed by vasodilatation and increased vascular permeability in response to histamine and other vasoactive mediators. Role of neutrophils The net result of this change in vascular permeability is an influx of polymorphonuclear cells (PMN) and monocytes in the injured area in a protein-

© 2009 Woodhead Publishing Limited

Wound management and dressings Phases of wound repair

Maximum response

I Inflammation

II Cell proliferation and matrix deposition

7

III Matrix remodelling

Fibroplasia Angiogenesis Re-epithelialization Extracellular matrix synthesis -Collagens Extracellular matrix -Fibronectin synthesis, degradation -Proteoglycans and remodelling Granulocytes ↑ Tensile strength Bleeding Phagocytosis ↓ Cellularity Coagulation ↓ Vascularity Platelet activation Complement activation Macrophages Cytokines

0.1

0.3

1

3 10 30 Days after wounding (log scale)

100

300

1.3 Wound biology: phases of wound repair.

rich fluid. Neutrophils phagocytise debris and bacteria, they also kill bacteria by releasing caustic proteolytic enzymes and free radicals in a process called ‘respiratory burst’.9 The surrounding tissue matrix in unwounded tissue is protected by protease inhibitors which can be overwhelmed and penetrated if the inflammatory response is extremely robust leading to damage to normal tissue. Unless stimuli for neutrophil recruitment persist at the wound site, the neutrophil infi ltration ceases after a few days, they undergo apoptosis and are engulfed and degraded by macrophages.10 Macrophages Macrophages start appearing in the wound two days after the injury and dominate the wound cell population over the next few days. Beside resident macrophages, the majority of macrophages at the wound site are recruited from the blood. Monocytes extravasate from the blood vessel, become activated and differentiate into mature tissue macrophages. Macrophages are crucial to wound healing and perform a number of functions. They act as antigen-presenting cells and remove debris and dead cells by phagocytosis. Perhaps their more important role in the process of healing is synthesis of numerous potent growth factors, such as TGF-β, TGF-α, basic fibroblast growth factor (bFGF), platelet-derived growth factor, and vascular endothelial growth factor, which promote cell proliferation and the synthesis of extracellular matrix molecules by resident skin cells.11 These factors also help in angiogenesis, migration and activation of

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Advanced textiles for wound care

fibroblast thus setting the stage of proliferation.12 It has been shown experimentally that macrophage depletion using antisera results in a significant delay in healing.13 Role of inflammatory mediators Inflammatory mediators play a central and major role in the process of wound healing. They include a collection of soluble factors present either in plasma in an inactive form or released by damaged and nearby cells and leukocytes in an attempt to control the damage and initiate healing. Mechanisms of inflammatory resolution Inflammation performs several important functions. It clears the wound of infectious organism and debris, and brings about a change in the micro-environment of the wound to set the stage for proliferation. However, successful repair after injury requires resolution of the inflammatory response. The mechanisms controlling this down-regulation of the inflammatory response are poorly understood and for years it was thought that the inflammatory response would just ‘burn itself out’. Recent evidence, however, suggests that this process is organised as a series of reactions to produce stop signals referred to as ‘check point controllers of inflammation’.14 Lipoxins and aspirin-triggered lipoxins are the stop signals for inflammation. Autocoids also display potent anti-inflammatory actions and are termed resolvins.15 Down-regulation of pro-inflammatory mediators and the reconstitution of normal microvascular permeability, which contributes to the cessation of local chemoattractants, synthesis of antiinflammatory mediators, apoptosis, and lymphatic drainage also play their role. An excessive or prolonged inflammatory response results in increased tissue injury and poor healing.

1.3.6 Proliferation This phase starts around the second or third day after injury and continues for up to 3 or 4 weeks. This is marked by the appearance of fibroblasts in the wound and overlaps with the inflammatory phase. As in other phases, the changes in this phase do not occur in a series, but overlap in time. Granulation tissue formation Fibroblasts start to appear in the wound from the third to fourth day and their numbers peak between the seventh and fourteenth days. They migrate from the wound margins using the fibrin-based provisional matrix created

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during the inflammatory phase of healing. Under the influence of bFGF, TGF-β, and PDGF secreted by macrophages they proliferate and synthesise glycosaminoglycans and proteoglycans, elastins and fibronectin, the building blocks of the new extracellular matrix of granulation tissue, and collagen. As the number of macrophages diminishes, fibroblasts themselves begin to secrete bFGF, TGF-β, and PDGF. They also begin producing keratinocyte growth factor and insulin like growth factor I. After secretion of collagen molecules, they are organised in the form of collagen fibres which are then cross-linked into bundles. Collagen gives the wound its tensile strength and, in addition, cells involved in inflammation, angiogenesis, and connective tissue construction attach to, grow and differentiate on the collagen matrix laid down by fibroblasts.16 Collagen deposition increases the tensile strength of the wound. Initially collagen levels in the wound increase, but later on homeostasis is reached as the collagen is also being degraded by collagenases. Angiogenesis Angiogenesis accompanies the fibroplasia phase and is essential to scar formation. Endothelial cells located at intact venules are stimulated by vascular endothelial growth factor (VEGF) which is secreted mainly by keratinocytes at the wound edge and also by macrophages, fibroblasts and platelets in response to hypoxia and the presence of lactic acid. Endothelial cells originating from parts of uninjured blood vessels develop pseudopodia and push through the extracellular matrix (ECM) into the wound site. They produce the degradation agents including plasminogen activator and collagenase and invade the wound by the enzymatic degradation of fibrin clot once the new granulation tissue (i.e., extracellular matrix, collagen, capillaries) is laid down.17 Through this activity, they establish new blood vessels which later on join to form capillary loops and establish blood flow in the wound. Cells, when adequately perfused, stop producing angiogenic factors, and migration and proliferation of endothelial cells is reduced.17 Eventually, blood vessels that are no longer needed die by apoptosis; this explains the change in color seen in scar tissue as it matures. Epithelialisation The initial event in epithelialisation is migration of undamaged epithelial cells from the wound margins. Keratinocytes at the wound edges are stimulated by EGF and TGF-α produced by activated platelets and macrophages,15 they proliferate and begin their migration across the wound bed within 12 to 24 h after injury.18 The fi rst step of migration involves separation of the keratinocytes from each other and their anchors to the cell

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basement membrane.19 The process of migration continues until the migrating cells from opposing sides of the wound touch each other. At the point of contact, migration ceases in a process known as contact inhibition.19 Once this process is complete, keratinocytes stabilise them by forming firm attachments to each other and the new basement membrane. 20 All these changes in the wound lead to the formation of granulation tissue which consists of inflammatory cells, fibroblasts and new vasculature in a hydrated matrix of glycoproteins, collagen and glycosaminoglycans, the components of a new, provisional ECM. The provisional ECM is different in composition from the ECM in normal tissue and includes fibronectin, collagen, glycosaminoglycans and proteoglycans. 21 Contraction About a week after the injury, the fibroblast differentiates into myofibroblasts, pulls the edges of the wound together and the wound begins to contract. 22 Contraction peaks at 5 to 15 days post wounding and continues even after the wound is completely re-epithelialised. 23 Contraction reduces the size of the wound and, thus, reduces the amount of ECM needed to fi ll the wound 24 and facilitates re-epithelialisation by reducing the distance which migrating keratinocytes must travel. At the end of the granulation phase, fibroblasts begin to undergo apoptosis, converting granulation tissue from an environment rich in cells to one that consists mainly of collagen.23

1.3.7 Maturation and remodelling Maturation and remodelling of the collagen into an organised and wellmannered network is the fi nal stage of the healing process (from day 8 up to 2 years). If this is compromised, then the wound’s strength will be greatly affected. On the other hand, excessive collagen synthesis can lead to the formation of a hypertrophic scar or keloid. The maturation phase can last for two years or longer, depending on the size of the wound and whether it was initially closed or left open. This phase is characterised by the removal of type III collagen and its replacement by mature type I collagen. There is a rapid production of type I collagen but there is no net gain as the old collagen is also being degraded by collagenases. New collagen fibres are rearranged, cross-linked, and aligned along tension lines but they can never become as organised as the collagen found in uninjured skin. 25 The second characteristic feature of this stage is programmed cell death or apoptosis and, thus the number of cell types such as macrophages, keratinocytes, fibroblasts, and myofibroblasts is reduced.18,20 Remodelling is regulated by fibroblasts through the synthesis of ECM components and MMPs that control cell

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differentiation. 26 All of these changes produce a cell-deficient environment with excessive connective tissue. Blood vessels that are no longer required die by apoptosis and the remainder acquire a basement membrane and become relatively impermeable. All of these factors lead to the increase in tensile strength, decrease in erythema and scar tissue bulk, and the fi nal appearance of the healed scar.

1.4

Factors affecting wound healing: why wounds fail to heal

In most cases, wound healing is a natural, uneventful process which leads to the restoration of tissue integrity. But, in some cases, wounds fail to heal and become a complex medical problem requiring specialised care and treatment. If a wound has not improved significantly in four weeks, or if it has not completed the healing process in eight weeks, it is considered a chronic, non-healing wound. Wound healing is dependent on the interaction of different cells, mediators and growth factors. Alterations in one or more of these components may account for the impaired healing observed in chronic wounds. Chronic wounds may be arrested in any of the healing phases but, most commonly, disruption occurs in the inflammatory or proliferative phase27 with the accumulation of excessive extracellular matrix and matrix metalloproteinases such as collagenase and elastase, which result in premature degradation of collagen and growth factors. 28 An optimum microenvironment and the absence of cytotoxic factors are essential for healing of wounds. Many local and systemic factors have been implicated in the delayed healing of wounds.

1.4.1 Local factors Infection Infection is the commonest local cause for delayed wound healing. Bacteria delay wound healing by activating the alternative complement pathway and exaggerating and prolonging the inflammatory phase of wound healing. The bacteria, themselves elaborate toxins and proteases, also compete for oxygen and nutrients, and this ultimately damages the cells. Tissue ischaemia Local hypoxia is detrimental to cellular proliferation, resistance to infection and collagen production. This may be the result of foreign bodies, infection, suture material, or the presence of peripheral vascular disease.

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Poor surgical technique Proper tissue handling and closure with appropriate sutures is very important. Wound healing is affected if the tissues are devitalised, strangulated with sutures or improperly debrided. Others Formation of haematomas, presence of foreign bodies and mechanical pressure are some of the other local factors in the pathophysiology of delayed wound healing.

1.4.2 Systemic factors Ageing Healing in the elderly is generally delayed but the fi nal result is qualitatively similar in elderly people. There are many physiological changes associated with ageing which can lead to delayed healing. Reduced skin elasticity and collagen replacement influence healing. Reduced immunity and other chronic diseases can also affect the healing process. Nutritional status Deficiency of various nutrients and vitamins can affect the wound healing process. Proteins are required for all the phases of wound healing and are particularly important for collagen synthesis. In protein deficiency states, cellular and humoral immune responses are blunted, fibroplasia and all aspects of matrix formation are delayed. Glucose balance is essential for wound healing and it provides the energy required for cell function. Insulin may act as a fibroblast growth factor and its deficiency leads to suppression of collagen deposition in the wound. 29 Deficiency of fatty acids can also impair healing. Vitamins Vitamin A deficiency has been associated with slowed re-epithelisation, decreased collagen synthesis and stability and an increased susceptibility to infection. Vitamin C (ascorbic acid) is an essential cofactor during collagen biosynthesis. In scurvy, the collagen formed is unhydroxylated, relatively unstable and subject to collagenolysis. Vitamin K deficiency results in a deficiency in the production of the clotting factors (factors II, VII, IX and X) that are vitamin K dependent

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resulting in bleeding diathesis, hematoma formation and secondary detrimental effects on wound healing. Iron is required to transport oxygen. Other minerals like zinc and copper are important for enzyme systems and immune systems. Zinc deficiency contributes to disruption in granulation tissue formation. Underlying diseases Diabetes, arthritis, renal disease, heart disease, cancer, immune disorder, lung disease blood disorders and surgery all affect the process of wound healing. Medication Anti-inflammatory, cytotoxic, immunosuppressive and anticoagulant drugs all reduce healing rates by interrupting cell division or the clotting process.

1.5

Wound healing: treatment options

1.5.1 Basic care Wound repair requires the timed and balanced activity of inflammatory, vascular, connective tissue, and epithelial cells and their mediators. It is important to provide an environment that is conducive to wound healing, to treat the underlying origin of the wound, and to correct associated abnormalities.

1.5.2 Wound dressings Dressings do not heal wounds; properly selected dressings do, however, promote healing and prevent further harm to the wound. Wound dressings are passive, active or interactive. 30 Passive dressings simply provide cover while active or interactive dressings are believed to be capable of modifying the physiology of the wound environment. Interactive dressings include hydrocolloids, hydrogels, alginates and foams. An ideal dressing should maintain a moist environment at the wound interface and act as a barrier to micro-organisms. Commonly available dressings include. Alginate These dressings are highly absorbent and are composed of calcium and sodium salts of alginic acid, obtained from seaweed. They are useful in

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medium to heavily exuding wounds and are also good for bleeding wounds. Examples include Kaltostat, Sorbsan and Algisite. Hydrogels Hydrogels have a high water content which creates a moist wound surface and helps in the debridement of wounds by hydration and promotion of autolysis. As absorption of exudate is poor, they can cause maceration. Examples include Aquafoam, Intrasite, Nu-Gel, Purilon and Sterigel. 31 Hydrocolloids Hydrocolloids are composed of a matrix of cellulose and other gel-forming agents, including gelatin and pectin. These dressings promote autolysis and aid granulation. Examples include sheets such as Alione, Combiderm and Duoderm; paste such as GranuGel; and hydrofibre such as Aquacel and Versiva. 31 Semipermeable fi lms Semipermeable dressings are good for low to medium exuding wounds. Examples include Opsite, Flexiguard, Tegaderm, Melfilm and Bioclusive. Foam dressings Foam dressings are useful for moderately exudating wounds as they prevent ‘strike through’ of exudate to the wound surface. They also provide cushion and support to the wound. Examples include Allevyn, Lyofoam, Tielle plus and Biatin Adhesive. Antimicrobial dressings Antimicrobial dressings are good for infected wounds especially in diabetics. Examples include Acticoat, Aquacell Ag, Arglaes, Inadine and iodoflex.

1.5.3 Bioengineered skin Bioengineered skin is generally divided into: 1. 2.

permanent, such as autografts and temporary, such as allografts (including de-epidermised cadaver skin and in vitro reconstructed epidermal sheets), xenografts (i.e. conserved pig skin) and synthetic dressings

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Allogenic grafts are produced from neonatal fibroblasts and keratinocytes. Available in the form of dermal, epidermal or composite grafts, they are better than traditional skin grafts as they are non-invasive, do not require anaesthesia and avoid potential donor site problems. Epidermal grafts Available in both autograft and allogenic forms, epidermal grafts include Epicell, Laserskin, CellSpray, Bioseed-S and LyphoDerm. 27 They are useful for coverage of large skin defects with acceptable cosmetic results and are indicated for burns and leg ulcers. Their main disadvantages include fragility and difficulty in handling owing to a lack of backing material. They are unsuitable for deep wounds as they only provide temporary cover. They are most successful when placed on a dermal bed. Dermal grafts Dermal grafts are either cellular or acellular, and allogenic in nature, and, hence, available for immediate use. Products include Integra, Alloderm, Biobrane, Transcyte and Dermagraft.27 They are indicated for burns, deep wounds, and for cosmetic procedure. However, they cannot be generated in large quantities and are susceptible to infections. Composite grafts Composite grafts are bilayered skin grafts and contain epidermal and dermal components. Apligraft is a commercially available product and is indicated for diabetic and venous ulcers. It lacks skin adnexal structures but produces all the cytokines and growth factors that are produced by normal skin. Allergy to bovine collagen, limited shelf-life and infection can limit their use. 27

1.5.4 Non-surgical innovations Vacuum assisted closure Vacuum-assisted closure (VAC) therapy entails placing an open-cell foam dressing into the wound cavity and applying a controlled subatmospheric pressure. This produces negative pressure in the wound, leading to improved blood flow and oxygenation. It also helps in removing excessive fluid and slough. 32 This stimulates granulation tissue formation, wound contraction and early closure of wound.

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Intermittent pneumatic compression This is an effective treatment for chronic ulcers on legs with severe oedema. It provides compression (at 20–120 mm Hg) at preset intervals. 33 It improves lymphatic and venous flow and helps in the healing of chronic ulcers. Hyperbaric oxygen Hyperbaric oxygen is thought to expedite healing as it has been shown that ischaemic lesions heal less well34 and certain growth factors do not work in hypoxic conditions. 35 Debate continues on its value in certain wound conditions. Other therapies Laser, ultrasound, hydrotherapy, versijet, electromagnetic therapy and electrotherapy are some other therapies which are used to stimulate healing.

1.5.5 Drug therapy Drugs affect wound healing by assisting or interfering with specific phases. Drugs can reduce peripheral vascular resistance, reduce blood viscosity and cause local or systemic vasodilatation leading to improved tissue perfusion and oxygenation. Currently available drugs include pentoxifylline, which decreases platelet aggregation leading to decreased viscosity and improved capillary microcirculation. It is useful in patients with chronic venous ulcers who cannot tolerate compression. Iloprost a vasodilator and prostacyclin analogue is good in the treatment of arterial and vasculitic ulcers. 33 Calcium channel blockers and glyceryl trinitrate (GTN) ointment have also been used as vasodilators in cases of vaculitic ulcers caused by Raynaud’s disease and ischaemic ulcers, respectively.

1.5.6 Growth factors Growth factors are soluble signalling proteins which influence wound healing through their inhibitory or stimulatory effect during different stages of the wound healing process. Produced by different cells they act on inflammatory cells, fibroblasts, and endothelial cells to direct the processes involved in wound healing. Recombinant human-platelet derived growth factor-bb (rhPDGF-BB, Becaplermin) is the only FDA-approved

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growth factor available for clinical use. In clinical trials, this has been shown to increase the incidence of complete wound closure and decrease the time to achieve complete wound healing. Basic fibroblast growth factor (available commercially in Japan) stimulates endothelial cell migration and proliferation. Its topical application leads to faster granulation tissue formation and epidermal regeneration in burn wounds. However, this effect is not seen in diabetic foot ulcers. Preclinical trials have shown promising results for epidermal growth factor and keratinocyte growth factor in venous ulcers and fibroblast growth factor platelet derived growth factor (PDGF) for pressure ulcers. Despite promising preclinical data, results of the clinical trials are disappointing. Inherent instability of these proteins in the hostile environment of the wound makes them ineffective. Time of application, dosage, mode of delivery or the combination of the growth factors may be incorrect and further evaluation is required.

1.6

Future trends

1.6.1 Gene therapy To be clinically effective a high concentration of growth factors is needed, which requires frequent and high dosing, but it is prohibitively expensive. Introduction of the gene rather than the product (growth factor) is thought to be cheaper and more efficient in treating non-healing wounds. It can lead to a sustained local availability of these proteins and can be cost effective. The technology to introduce genes through physical or biological vectors has existed for some time. Long-term expression of the therapeutic gene remains a challenge but only a transient gene expression is required for wound repair. Phase I studies are being conducted at the moment and their results will dictate any further course of action in this field.

1.6.2 Stem cells therapy Stem cells which are thought to be present in every tissue are characterised by their prolonged self-renewal capacity and by their asymmetric replication. There is potential that stem cells may reconstitute dermal, vascular and other elements required for optimum wound healing. Han et al.36 showed the potential of human bone marrow stromal cells to accelerate wound healing in vitro by measuring the amount of collagen synthesis and the levels of basic fibroblast growth factor. Though the technique is still in its infancy, Badiavas et al.37 have shown that direct application of autologous bone marrow and its cultured cells may accelerate the healing process.

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1.7

Conclusions

Chronic wounds do not have a unique defect but a number of factors, which, when present in combination, lead to the non-healing of wounds. Wound management should therefore be multifactorial and aim at correcting the underlying abnormalities. No single treatment is universally effective owing to multiple molecular and cellular events involved and a combination of different therapies is required.

1.8

References

1. robson mc, Wound infection: a failure of wound healing, caused by an imbalance of bacteria. Surg Clin North Am 1997; 77:637–50. 2. janis je and attinger ce, Current concepts in wound healing. Plast Reconstr Surg 2006; 117(7 Suppl):4S–5S. 3. attinger ce, janis je, steinberg j, schwartz j, al-attar a and couch k, Clinical approach to wounds: debridement and wound bed preparation including the use of dressings and wound-healing adjuvants. Plast Reconstr Surg 2006 Jun; 117(7 Suppl):72S–109S. 4. iocono ja, ehrlich hp and gottrup f et al., The biology of healing. In: DL Leaper and KG Harding, Editors, Wounds: biology and management, Oxford University Press, Oxford, England (1998), pp. 12–22. 5. kerstein md, The scientific basis of healing. Adv Wound Care 1997; 10(4):30–36. 6. singer aj and clark ra, Cutaneous wound healing, N Engl J Med 1999; 341:738–746. 7. beck e, duckert f and ernst m, The influence of fibrin stabilizing factor on the growth of fibroblasts in vitro and wound healing. Thromb Diath Haemorrh 1961; 6:485. 8. haas af, Wound healing, Dermatol Nurs 1995; 7:28–34. 9. greenhalgh dg, The role of apoptosis in wound healing. The International J Biochem Cell Biol 1998; 30(9):1019–1030. 10. martin p and leibovich sj, Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 1998; 15(11):599–607. 11. dipietro la and polverini pj, Role of the macrophage in the positive and negative regulation of wound neovascularisation. Am J Pathol 1993; 143:678–684. 12. witte m and barbul a, Role of nitric oxide in wound repair. Am J Surg 2002; 183:406. 13. leibovich sj and ross r, The role of the macrophage in wound repair. Am J Pathol 1975; 78:71–100. 14. trengove nj, stacey mc and macauley s, Analysis of acute and chronic wound environment: The role of protease and their inhibitors. Wound Repair Regen 1999; 7:442. 15. lawrence w and diegelmann r, Growth factors in wound healing. Clin Dermatol 1994; 12:157. 16. ruszczak z, Effect of collagen matrices on dermal wound healing. Adv Drug Deliv Rev 2003; 55(12):1595–1611.

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17. greenhalgh dg, The role of apoptosis in wound healing. Int J Biochem Cell Biol 1998; 30(9):1019–1030. 18. iocono ja, ehrlich hp and gottrup f et al., The biology of healing. In: DL Leaper and KG Harding, Editors, Wounds: Biology and Management, Oxford University Press, Oxford, England (1998), pp. 12–22. 19. garrett b, Re-epithelialisation, J Wound Care 1998; 7:358–359. 20. clark raf, Wound repair: Overview and general considerations (ed 2). In: RAF Clark, Editor, The Molecular and Cellular Biology of Wound Repair, Plenum Press, New York, NY (1995), pp. 3–50. 21. ruszczak z, Effect of collagen matrices on dermal wound healing. Adv Drug Del Rev 2003; 55(12):1595–1611. 22. eichler mj and carlson ma, Modeling dermal granulation tissue with the linear fibroblast-populated collagen matrix: A comparison with the round matrix model. J Dermatol Sci 2005; 41(2):97–108. 23. stadelmann wk, digenis ag and tobin gr, Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg 1998; 176(2):26S–38S. 24. calvin m, Cutaneous wound repair, Wounds 1998; 10:12–15. 25. lorenz hp and longaker mt, Wounds: biology, pathology, and management. Stanford University Medical Center, 2003. 26. streuli c, Extracellular matrix remodeling and cellular differentiation, Curr Opin Cell Biol 1999; 11:634–640. 27. enoch s, grey je and harding kg, Recent advances and emerging treatments. BMJ Apr 2006; 332:962–965. 28. diabetes care, american diabetes association. Consensus development conference on diabetic foot wound care. 1999; 22:1354–1360. 29. eaglestein wh and mertz pm, ‘Inert’ vehicles do affect wound healing. J Invest Dermatol 1980; 74:90. 30. hanson c, Interactive wound dressings. A practical guide to their use in older patients. Drugs Aging 1997; 11:271–284. 31. jones v, grey je and harding kg, Wound dressings. BMJ Apr 2006; 332:777–780. 32. fleck tm, fleck m, moidl r, czerny m, koller r, giovanoli p, hiesmayer mj, zimpfer d, wolner e and grabenwoger m, The vacuum-assisted closure system for the treatment of deep sternal wound infections after cardiac surgery. Ann Thoracic Surg 2002, 74(5):1596–1600. 33. enoch s, grey je and harding kg, Non-surgical and drug treatments. BMJ Apr 2006; 332:900–903. 34. jonsson k, hunt tk and mathes sj, Oxygen as an isolated variable influences resistance to infection. Ann Surg 1988; 208(6):783–787. 35. wu l et al., Effects of oxygen on wound responses to growth factors: Kaposi’s FGF but not basic FGF stimulates repair in ischemic wounds. Growth Factors 1995; 12(1):29–35. 36. han sk et al., Potential of human bone marrow stromal cells to accelerate wound healing in vitro. Ann Plast Surg 2005; 55:414–419. 37. badiavas ev and falanga v, Treatment of chronic wounds with bone marrowderived cells. Arch Dermatol 2003; 139(4):510–516.

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2 Testing dressings and wound management materials S. T. T HOM A S, formerly of Surgical Materials Testing Laboratory, Medetec, UK

Abstract: The development of modern dressings is briefly reviewed and a description is given of how new test methods and specifications have evolved to characterise various key aspects of the performance of the products concerned. For thousands of years man has applied a variety of materials to his wounds to control bleeding and promote healing. For much of that time many of the materials used were largely those that occurred naturally, or which were developed and used primarily for another purpose. Only in the last thirty to fi fty years have large number of increasing complex products been developed specifically for application to open wounds of all types. These new dressings vary widely in composition and construction and, as a result, new families of performance-based test methods and specifications have been developed in order in order to characterise their performance. Key words: wound dressings, wound management, fluid handling, hydrocolloids.

2.1

Introduction

The use of materials to cover or treat wounds stretches back into antiquity but the use of standards and specifications to characterise these materials is relatively new. The fi rst standards that were used to characterise dressings were very simple and concentrated primarily upon the structure rather than the function of the products concerned. As new, ever-more sophisticated dressings were introduced, there was an increasing need for test systems to demonstrate that these materials perform in a consistent manner and delivered the performance claimed for, and expected of them. Whilst it is undoubtedly true that ultimately it is how a product performs clinically that will determine its acceptability and commercial success, well-designed laboratory tests can provide a useful performance indicator, particularly in comparative terms. In this chapter, the need for dressing standards is discussed and how these standards have evolved, and briefly outlines test methods that can be 20

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used to assess key aspects of the performance of many different types of products.

2.2

The need for laboratory testing

Laboratory tests for dressings are required for a number of reasons: •

To demonstrate compliance with national or international standards or specifications. • To ensure product meets ‘in-house’ manufacturing standards. • To facilitate comparisons with competitive products. • To generate data to support allocation of shelf life (stability/storage). There are essentially three types of standards or specifications.

• Structural standards, which defi ne the structure and/or composition of a product. • Performance standards, which describe one or more key aspects of the function of a dressing. • Safety standards, designed to ensure that a product, when used appropriately, is unlikely to adversely affect the health or wellbeing of the individual to whom it is applied.

2.2.1 The development of dressings For centuries mankind had little option but to apply readily available natural substances to his wounds to staunch bleeding, absorb exudate or promote healing. Initially, these would have consisted of simple materials such as honey, animal oils or fat, cobwebs, mud, leaves, moss or animal dung applied in the crude form in which they were found, but later these and other ‘raw materials’ began to be combined together, either to make them easier to handle, or to improve their clinical effectiveness. Whilst most of these early preparations were probably of little or no value, others, such as honey, used alone or mixed with oils or waxes, undoubtedly conferred some real clinical benefits to the user. Up to the end of the 19th century, whenever dressings were required to cover wounds, absorb exudate or remove blood during a surgical procedure, practitioners of the time used whatever materials were to hand, often recycling old pieces of cloth or linen fabric for this purpose. This was sometimes fi rst unravelled to form short ends of thread called ‘charpie’, or the surface was scraped with knives to produce ‘soft lint’, a soft fluffy material not dissimilar to absorbent cotton (cotton wool) which could be used to pack cavities and soak up exudate or blood. The fi rst product to be manufactured commercially for use as a dressing was absorbent (sheet) lint. This was formed by scraping sheets of old linen

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with sharp knives to raise a fibrous ‘nap’ on one surface, increasing the absorbency of the cloth but decreasing its tensile properties. Initially a manual process, a lint-making machine was developed in the fi rst half of the 19th century which used new, specially woven, fabric for the purpose. This resulted in a more consistent product with, it is assumed, a considerably lower bioburden! Originally lint was formed from linen but this was eventually replaced by cotton by the middle of the 20th century.

2.2.2 The first standards for dressings As new types of dressings were developed and the production of surgical materials became more mechanised, it became necessary to develop formal standards to ensure that these were consistently produced to an agreed of level of quality. The fi rst of these appeared in two supplements to the British Pharmaceutical Codex (BPC) of 1911 and these were later incorporated into the 1923 edition of this publication. Over 80 products were described, the majority of which consisted of cotton fibre, both medicated and unmedicated, and a variety of cotton fabrics together with a few more complex products such as emplastrums (plasters) and oiled silk. The BPC remained the principal source of standards for surgical dressings within the United Kingdom for over 50 years, but, in 1980, these were transferred to the British Pharmacopoeia (BP). When, as a result of European legislation, dressings became classified as Medical Devices, monographs for these materials were subsequently omitted from the BP.

2.2.3 The importance of performance-based specifications The early pharmacopeial monographs consisted almost entirely of structural specifications supplemented by limit tests for potential contaminants. Whilst such standards undoubtedly have a value as quality control checks to ensure that products which have previously been shown to meet a specific clinical need are produced in a consistent way from a range of well-characterised materials, they do not facilitate comparisons between the performances of different types of dressings. Their proscriptive and inflexible nature also prevents or delays the introduction of new and more innovative products which may be structurally different from the standard materials. Recognising these limitations, in the early 1990s, the Surgical Dressings Manufacturing Association (SDMA) set up a series of working groups, comprising technical staff from the industry and the NHS, to devise a new family of performance-based test methods and specifications. These were based on a number of instances upon work that had been pioneered within the Surgical Materials Testing Laboratory (SMTL), an NHS facility that specialised in testing wound dressings and other medical disposables for the

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NHS in Wales. This group published test methods for bandages, alginates, fi lms, hydrocolloids and hydrogels, many of which subsequently became incorporated into the BP and/or adopted as European Standards. The types of tests required to characterise the performance of a dressing should be determined by the nature and condition of the wound to which the product is to be applied. The functions of a dressing have been described more fully in the past,1 but for the purpose of this chapter the principal requirements are summarised below. • • • • • •

Exudate management/environmental control Control or prevention of infection Provide a bacterial barrier Odour control Low-adherence Freedom from toxicity.

2.3

Fluid-handling tests

The effective management of the moisture content of a wound and the surrounding skin is perhaps the most important requirements of any dressing system. In the case of exuding wounds, this implies the removal of excess wound fluid, but, in dry or lightly exuding wounds, the dressing may be required to conserve moisture in order to maintain the exposed tissue in the optimum state of hydration to facilitate epithelialisation or promote autolytic debridement. The ability to control the loss of moisture from a wound is commonly determined by the moisture vapour permeability of the dressing or dressing system. Because excessive exudate can cause maceration of the periwound skin, which in turn can lead to infection, considerable attention has been given by the industry to the development of highly absorbent products that are able to prevent fluid from spreading over the surrounding healthy tissue. Some dressings, such as hydrophilic polyurethane fi lms, are very permeable to water vapour and thus permit the passage of a significant quantity of the aqueous component of exudate from the wound to the environment by evaporation. In practice, however, most permeable products are unable to cope with the volume of fluid that is produced by heavily exuding leg ulcers, burns or malignant wounds. In such situations, products that have the ability to absorb or otherwise retain significant quantities of liquid are required, although many also combine this absorptive function with a significant degree of moisture vapour permeability. These two values determine the ability of a dressing to cope with wound exudate and are described as its fluid handling capacity (FHC). 2 Numerous different tests have been described to characterise the fluid handling properties of dressings, which vary from simple ‘dunk and drip’

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Advanced textiles for wound care

tests to more sophisticated techniques in which a suitable test fluid is applied to a sample of dressing under controlled conditions, some of which have been incorporated in the European Standard (BS EN 13726-1) 3 described below.

2.3.1 Free swell absorptive capacity This, the fi rst standard test described in BS EN 13726-1, measures the uptake of fluid by fibrous dressings such as those made from alginate fibre presented either in sheet or rope form. The dressing is placed in a Petri dish together with a quantity of test solution equivalent to 40 times the weight of the test sample, and held for 30 min at 37 °C after which it is gently removed from the dish, allowed to drain for 30 s and reweighed. The absorbency is then expressed as the mass of solution retained per 100 cm 2 (for sheet dressings) or per gram of sample for cavity dressings. Unless otherwise stated, all absorbency tests are performed using ‘Test solution A’, a mixture of sodium chloride and calcium chloride solutions containing 142 mmol of sodium ions and 2.5 mmol of calcium ions as the chloride salts. This solution has an ionic composition similar to human serum or exudate. The presence of both sodium and calcium ions is required as these both have a marked effect upon the gelling characteristics of alginate fibres. It will immediately be seen that a serious criticism of this method is that the alginate is tested in the absence of any pressure, which means that the results obtained bear little relation to the volume of exudate that the dressing will take up under normal conditions of use. (This point is returned to later.) In the presence of sodium ions, alginate fibres absorb fluid and swell, sometimes taking on a gel-like appearance. The degree of swelling and dispersion is determined by the chemical structure, ionic content and method of preparation of the dressing. Some alginate products, having a high mannuronic acid content, appear to form an amorphous mass, whilst others with a high guluronic acid content tend to retain their structure and swell to a much lesser degree.4 These properties are quite important as they determine how the dressing will perform when introduced into a wound and BS EN 13726-1 describes two simple tests that help to characterise the alginate and determine its dispersion/solubility.

2.3.2 Fluid-handling capacity This test, also described within BS EN 13726-1, and based on a method published previously, 5 provides information on the amount of test fluid

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Testing dressings and wound management materials

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both retained and transpired by products such as hydrogel and hydrocolloid sheets and other dressings made from foam which incorporate an integral waterproof backing layer. The method is not suitable for testing fibrous products or permeable absorbents. The test involves the use of a simple piece of apparatus known as a Paddington Cup. This is described in detail in the standard, but, essentially, it consists of a cylinder with an internal cross-sectional area of 10 cm 2 having a flange at each end. To one end of the cylinder is fitted an annular ring, the internal diameter of which is identical to that of the cylinder, and, to the other, a solid plate, which can be clamped into position forming a watertight seal. A piece of dressing under examination is cut to shape and clamped between the annular ring and one of the flanges. The cylinder together with all the associated parts is then weighed. Approximately 20 ml of test fluid is added to the cup and the plate clamped in position. The cup is then weighed again before being placed in an incubator capable of maintaining the internal temperature and humidity within specified limits (37 ± 1) °C and relative humidity