Principles and Practice of Wound Care

(Trang không có chữ)

Principles and Practice of
Wound Care
JAYPEE BROTHERS MEDICAL PUBLISHERS (P) LTD
New Delhi • Panama City • London
®
Sujata Sarabahi MS MCh DNB (Plastic Surgery) MNAMS
Associate Professor and Senior Plastic Surgeon
Department of Burns, Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and Safdarjung Hospital
New Delhi, India
VK Tiwari MS MCh
Professor and Consultant Plastic Surgeon
Department of Burns, Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and Safdarjung Hospital
New Delhi, India
Foreword
SP Bajaj
Editors

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should consult with a specialist or contact the manufacturer of the drug or device.
Principles and Practice of Wound Care
First Edition: 2012
ISBN  978-93-5025-864-4
Printed at
®

Dedicated to
The fond memory of
(Padmashree) Late Dr LC Gupta
Our Guide and Mentor
who continues to be a constant source of encouragement
and inspiration and without whose guidance this work
would not have seen the light of the day.
We are also thankful to our family members for their patience and support

(Trang không có chữ)

Contributors
Ashok Damir  MD (Foot Fellowship) DSCPM (Chicago)
Senior Diabetic Foot Specialist
Fortis C-DOC
New Delhi, India
drashokdamir@yahoo.com
Atul Shah  MS MCh (Plastic Surgery)
Professor of Plastic Surgery
Grant Medical College
Sir JJ Group of Hospitals
Byculla, Mumbai
Maharashtra, India
atulshah08@hotmail.com
Chintamani  MS FRCS (Edin) FRCS (Glas) FRCS (Ire) FACS FICS FIAMS
Professor
Department of Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
chintamani7@rediffmail.com
Deepak Balasubramanian  MS DNB
Fellow
Head and Neck/Plastic Reconstructive Surgery
Amrita Institute of Medical Sciences
Kochi, Kerala, India
deepakbala@live.com
Deepak Nanda  MS MCh (Plastic Surgery)
Associate Professor and Senior Plastic Surgeon
Department of Burns,
Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
drdeepaknanda@gmail.com
Durga Karki  MS MCh DNB (Plastic Surgery) MNAMS
Assistant Professor
Department of Burns,
Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
dkarki10@yahoo.co.in
Anshumali Mishra  MS
Senior Resident
Department of Burns, Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
dramisra@gmail.com
Anurag Agarwal  MBBS DNB (Surg) MNAMS
Consultant
Division of Peripheral Vascular and
Endovascular Sciences
Medanta—The Medicity Hospital
Gurgaon, Haryana, India
anurag_7@yahoo.com
Arun Goel  MS MCh FICS
Consultant Plastic Surgeon and Head
Department of Burns, Plastic and Maxillofacial Surgery
Lok Nayak Hospital
Associated Maulana Azad Medical College
New Delhi, India
dragoel@hotmail.com
Ashish Dey  MS (General Surgery)
Clinical Assistant
Department of General Surgery
Sir Ganga Ram Hospital
New Delhi, India
ashishdey_78@rediffmail.com
Ashish Kumar Duggal
Senior Medical Officer
Department of Medicine
Ram Manohar Lohia Hospital and Postgraduate Institute of
Medical Education and Research
New Delhi, India
ashishduggal2005@rediffmail.com
Ashish Rai  MS MCh (Plastic Surgery)
Assistant Professor
Department of Burns, Plastic and Maxillofacial Surgery
Postgraduate Institute of Medical Education and Research
and Ram Manohar Lohia Hospital
New Delhi, India
drashishrai@yahoo.co.in

Principles and Practice of Wound Care
viii
Harish Chellani  MD (Pediatrics)
Professor
Consultant Pediatrician
Department of Pediatrics
Vardhman Mahavir Medical College and
Safdarjung Hospital, New Delhi, India
chellaniharish@gmail.com
Harsh Mohan  MD FAMS FUICC FIC (Path)
Professor and Head
Department of Pathology
Government Medical College
Chandigarh, India
drharshmohan@gmail.com
Imran Ahmed  MS MCh (Plastic Surgery)
Reader
Department of Plastic Surgery
Aligarh Muslim University
Aligarh, Uttar Pradesh, India
drimran@rediffmail.com
Irneet Mundi  MD DNB
Senior Resident
Department of Pathology
Government Medical College
Chandigarh, India
Irneet04@yahoo.co.in
Karoon Agrawal  MS MCh (Plastic Surgery)
Director-Professor and Head
Department of Burns, Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital, New Delhi, India
karoonaparna@gmail.com
Krishna Asuri  MS
Senior Resident
Department of Trauma Surgery
All India Institute of Medical Sciences
New Delhi, India
drasurikrishna@gmail.com
Malini Capoor  MD (Microbiology)
Assistant Professor
Vardhman Mahavir Medical College and
Safdarjung Hospital, New Delhi, India
rajeevmalini@rediffmail.com
Maneesh Singhal  MS MCh (Plastic Surgery)
Associate Professor
Department of Trauma Surgery
All India Institute of Medical Sciences
New Delhi, India
drmaneesh@gmail.com
Mary Babu
Director Grade Scientist
Head of Biomaterials (Retd)
Central Leather Research Institute
Chennai, Tamil Nadu, India
babumary2000@yahoo.com
Megha Tandon
Department of Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
Mohit Sharma  MS MCh (Plastic Surgery)
Professor
Plastic and Reconstructive Surgery
Amrita Institute of Medical Sciences
Kochi, Kerala, India
mohitsharma@aims.amrita.edu
Moris Topaz  MD PhD
Head
Plastic Surgery Unit
Hillel Yaffe Medical Center
Hadera, Israel
mtopazmd@yahoo.com
NK Agrawal
Associate Professor
Department of Plastic Surgery
Institute of Medical Sciences
Banaras Hindu University
Varanasi, Uttar Pradesh, India
agrawalnk@yahoo.com
PG Raman  MD FRCP (Edin)
Retired Professor of Medicine
Mahatma Gandhi Memorial Medical College
Indore, Madhya Pradesh, India
Pratap Duggirala  MS
Senior Resident
Department of Burns, Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital,
New Delhi, India
doc.prathap@gmail.com
Pratima Anand  MD (Pediatrics)
Medical Officer
Department of Pediatrics
Vardhman Mahavir Medical College and
Safdarjung Hospital, New Delhi, India
drpratima08@yahoo.co.in

Contributors 
ix
Praveen Bhardwaj  MS MCh
Junior Consultant
Division of Plastic Surgery
Hand and Reconstructive Microsurgery and Burns
Ganga Hospital
Coimbatore, Tamil Nadu, India
drpb12@yahoo.co.in
PS Barooah
Senior Resident
Department of Medical Surgery
Institute of Medical Sciences
Banaras Hindu University
Varanasi, Uttar Pradesh, India
drpsbarooah@rediffmail.com
Rajiv Parakh  MS FRCS (Vascular Surgery)
Chairman
Division of Peripheral Vascular and Endovascular Sciences
Medanta—The Medicity Hospital
Gurgaon, Haryana, India
rparakh1@yahoo.co.in
Rakesh Kain
Assistant Professor
Department of Burns, Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
rakeshkain@rediffmail.com
Ram Shanmugam  BPT
Physiotherapist
Department of Orthopedics
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
ramshanmugam@ymail.com
Ranjith James Babu
Medical Officer
Department of Surgery
Gajanan Rao Multispecialty Hospital
Chennai, Tamil Nadu, India
ranjithjames2000@yahoo.co.in
RK Chittoria  MS MCh DNB MNAMS PhD
Additional Professor and Head
Department of Plastic Surgery
Sri Venkateswara Institute of Medical Sciences University
Tirupati, Andhra Pradesh, India
drchittoria@yahoo.com
Rohan Khandelwal
Department of Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
RS Mohil  MS
Consultant Surgeon and Associate Professor
Department of Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
rsmohil@gmail.com
S Bhattacharya
Postgraduate Student
Department of General Surgery
Institute of Postgraduate Medical Education and Research
and SSKM Hospital
Kolkata, West Bengal, India
drsiddharthabhattacharya@gmail.com
S Shanmuganathan
Professor
Department of Pharmaceutics
Faculty of Pharmacy
Sri Ramachandra University
Chennai, Tamil Nadu, India
shanmugganathan@yahoo.com
Sameek Bhattacharya  MS MCh (Plastic Surgery)
Assistant Professor
Department of Burns, Plastic and Maxillofacial Surgery
Postgraduate Institute of Medical Education and Research
and Ram Manohar Lohia Hospital
New Delhi, India
sameekb@gmail.com
Sandeep Mehta  MS MCh (Plastic Surgery)
Senior Plastic Surgeon
Rajeev Gandhi Cancer Institute
New Delhi, India
drmehtasandeep@rediffmail.com
Savita Arora  MS MCh (Plastic Surgery)
Associate Professor and Senior Plastic Surgeon
Department of Burns,
Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
groversavita@yahoo.com

Principles and Practice of Wound Care
x
Shalini Duggal
Junior Specialist
Department of Microbiology
Baba Saheb Ambedkar Hospital
New Delhi, India
shaliniduggal2005@rediffmail.com
S Raja Sabapathy  MS MCh DNB (Plastic Surgery)
Chairman
Division of Plastic Surgery
Hand and Reconstructive Microsurgery and Burns
Ganga Hospital
Coimbatore, Tamil Nadu, India
rajahand@vsnl.com
Sujata Sarabahi  MS MCh DNB (Plastic Surgery) MNAMS
Associate Professor and Senior Plastic Surgeon
Department of Burns,
Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
ssarabahi@yahoo.co.in
Sumit Arora  MS (Ortho) DNB (Ortho)
Department of Orthopedics
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
Sumit Batra  MS DNB (Orthopedics)
Assistant Professor
Department of Orthopedics
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
Sushma Sagar  MS
Associate Professor
Department of Trauma Surgery
All India Institute of Medical Sciences
New Delhi, India
sagar.sushma@gmail.com
TD Chugh
Chairman and Senior Consultant
Department of Microbiology
BLK Superspecialty Hospital
Pusa Road, New Delhi, India
chughtd@gmail.com
Thakur Thussu  MS
Senior Resident
Department of Burns,
Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
thakurthussu@rediffmail.com
V Bhattacharya  MS MCh (Plastic Surgery)
Professor
Department of Plastic Surgery
Banaras Hindu University
Varanasi, Uttar Pradesh, India
visweswar1@rediffmail.com
Vinod K Malik  MS (Gen Surg)
Senior Consultant and Vice Chairman
Department of General Surgery
Sir Ganga Ram Hospital
New Delhi, India
sumailk@yahoo.com
VK Tiwari  MS MCh
Professor and Consultant Plastic Surgeon
Department of Burns,
Plastic and Maxillofacial Surgery
Vardhman Mahavir Medical College and
Safdarjung Hospital
New Delhi, India
drvinaytiwari57@gmail.com

Foreword
Wounds are as old as the creation of the universe. Healing and repair of injured tissues is an integral part of all living structures
from the most basic single-cell structure to the most complex human body. The lower we go in the developmental order, the
more complete regeneration we see; while as we go higher in the strata, the process of regeneration becomes less while the
process of repair takes over.

Wounds have fascinated mankind; therefore, over time special groups of people developed to manage the wounds. These
people were termed as surgeons and in due course of time wounds and surgeons became synonymous. Wounds still remain a
problem in the healthcare world and more than 30 percent of the budget of any hospital is spent on materials which are used
for wound care. This may be a simple gauze or a bandage, antibiotics to stop infection, topical creams or ointments and other
­dressing materials to be applied over the wounds. This in association with different cleansing agents and antiseptic materials
takes away the major budget of any institution. No wonder maximum numbers of advancements have been made in different
types of wound care materials as all wounds are not alike and different wounds have different demands for their management.
However, there is a paucity of literature which could describe how different materials should be utilized.

Dr VK Tiwari and Dr Sujata Sarabahi should be complimented for bringing a comprehensive book on practical aspects of
wound care with full scientific principles. Both the editors are highly acclaimed plastic surgeons and have a lot of experience in
managing different types of wounds at one of the largest burns unit of the country. The layout of the book is simple and attracts
both, a very well-experienced person in wound management and those who are going to come in contact of a wound for the
first time. This is a multi-authored book and each contributor is an authority over the topic, they are writing about. The topics
chosen in the book practically cover all different types of wounds which are commonly known while sufficient space is given
for the historical grounding of wounds also, which starts with the beautiful work of Dr Savita Arora on the evolution of wound
care. The book provides an insight to the reader about how the wound care has changed from the initial medieval days to the
present day of a more scientific thinking.

Logically, these chapters move from the pathology of wound healing to the most recent advances and finally on the
management of scars and its maturation. Justifiably, there are some repetitions of the topics as the authors intended to cover
all the intricacies involved with these wounds. The topics of woundbed preparation by Dr RK Chittoria, and debridement and
preparation of wound by Dr Raja Sabhapathy, though fall in the same category require a separate mention as both the editors
have done justice to the job assigned to them. Dr Sushma Sagar has enlightened the reader about the life-threatening wounds
and has also given glimpses of problems of wounds.

The book covers practically all different types of wounds in detail, therefore, reader gets an idea of managing practically all
different types of wounds and how the treatment of one wound differs from the other.

The book has done justice by providing knowledge about the other factors influencing wound management which involves
nutrition, changes in environment either by negative pressure or by increasing the oxygen pressure.

I am confident that this unique book will be of immense significance and knowledge to all the surgeons and other health
personnels involved with wound management—nurses, technicians, research workers, etc.
SP Bajaj
MBBS MS MCh FRCS MNASc
Senior Consultant and Ex-Professor of Plastic Surgery
University of Delhi
Delhi, India

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Preface
While writing the preface of Principles and Practice of Wound Care, we are reminded of the world renowned messiahs in this
field, Mother Teresa and Florence Nightingale. Both are famous for spending time with patients, who become unacceptable in
the society because of their wounds and giving them their healing touch. They have indeed taught us how to be kind, caring and
loving while treating wounded patients.

A new book on wounds and wound care. Is it really needed? Has enough not been written on wound and wound care? The
answer is yes and no. Wounds have been the bête noir of the human race and clinicians since the time immemorial. Wound
management is a field which involves all specialties, yet, there is not a single department which takes full responsibility for
taking care of wounds. Generally, therefore, patients with wounds are found shunting between the departments dealing with the
cause and the plastic surgeons who are ultimately going to cover them. A comprehensive approach to wound care is thus lacking
and this is what this book sets out to achieve.

The book is an amalgamation of ideas from specialists from many departments. It provides a comprehensive and extensive
review of wound healing and its management, treatment and also its prevention. Therefore, all healthcare professionals who are
dealing with wounds in their day-to-day practice will find useful and advanced information and tips on handling them so that
they can provide optimal care.

The contents of the book cover all types of wounds and every aspect of wound management. Recent advances in wound
management have also been covered in detail along with each contributor’s own individual experiences in using different
modalities of treatment. The broad scope of the book endeavors to give an in-depth knowledge of wound management as well
as prevention; in other words, a holistic overview of wound care.

The subject of wound care now encompasses a very wide canvas from the age old physiology and pathology of wound and
wound healing to a plethora of wound care products each of which propose to have a unique mode of action and promote wound
healing. The book has chapters which deal with all the newer products delving in detail about their mechanism, role and utility
in wound healing allowing the reader to make an informed choice about these products, since there is a huge market building
up because of increased interest in wound care. However, all these newer products and latest technologies have to be evaluated
more realistically and used sensibly to get the best outcome.

One should never forget about the suffering of the patient due to the wound that he or she has. As clinicians, it is our
responsibility to see the wound not as a mere disease but as a process which has a bearing on the day-to-day life of the patient.
The treatment should, therefore, be quick, adequate and tailored specifically to suit the needs of individual patients. This is
only possible by a comprehensive effort from the healthcare professionals and by evolving a system wherein proper training is
imparted to all the personnels allowing them to optimally handle wounds.

The book has been written with these objectives and aims to be a comprehensive, yet lucid text on this complicated matter
of wound, wound healing and care.

We would like to thank all the contributors for sharing their knowledge and clinical experience with the readers. We are all
part of this fast-changing world and cannot remain behind. Let us change our thinking for change is life. We wish good luck to
all our readers!
Sujata Sarabahi
VK Tiwari

(Trang không có chữ)

Contents
Section 1: History and Healing
1. Evolution of Wound Care...............................................................................................................................3
Savita Arora
•  Ancient Medical Practice (460–136 BC)  3  •  Middle Ages (476 AD–1453)  6  •  Modern Ages  7 
•  Recent Advances in Wound ­Coverage  9
2. Pathology of Wound Healing.......................................................................................................................11
Harsh Mohan, Irneet Mundi
•  Wound Healing  11  •  Phases of Wound Healing  11  •  Types of Wound Healing  16 
•  Factors Influencing Healing  16  •  Complications of Wound Healing  17  •  New Horizons  17
3. Recent Advances in Wound Healing..........................................................................................................19
Mary Babu, Ranjith James Babu, S Shanmuganathan
•  Hemostatic Phase  19  •  Inflammatory Phase  20  •  Proliferative Phase  20  •  Remodeling Phase  21 
•  Fibrotic/Chronic Wounds  21  •  Management of Fibrotic Wounds  21  •  Chronic Ulcers and its Implications  21 
•  Wound Dressing and its Characteristics  22  •  Skin Substitutes  23  •  Tissue Engineering  23  •  Stem Cells  23
4. Scars Following Wound Healing.................................................................................................................27
Sujata Sarabahi, Pratap Duggirala
•  Classification  27  •  Hypertrophic Scars versus Keloids  29  •  Scar Assessment  31  •  Management  34
5. Classification of Wounds............................................................................................................................42
RS Mohil
•  Contused and Lacerated Wounds  43  •  Bruise, Contusion and Hematoma  43  •  Puncture Wounds  44 
•  Bite Wounds  44  •  Traction and Avulsion Injuries  46  •  Crush Injuries and Compartment Syndrome  46 
•  Ulcer  47  •  Healing of Wounds  48
Section 2: General Principles for Wound Management
6. Wound Bed Preparation (Guidelines of International Advisory Board for WBP)...................................53
RK Chittoria
•  Definition  53  •  Origin  53  •  Importance  53  •  Principles  53
7. Initial Management of Life-­threatening Wounds.......................................................................................59
Sushma Sagar, Krishna Asuri, Maneesh Singhal
•  Definition  59  •  Classification  59  •  Etiopathogenesis  61  •  Clinical Features  61  •  Management  62
8. Debridement—Preparing the Wound Bed for Cover.................................................................................68
S Raja Sabapathy
•  Evolution of Concepts—Serial Debridement vs Radical Debridement  68  •  Technique of Debridement  69 
•  Role of Wound Swabs  73  •  Role of Antibiotics and Tetanus Prophylaxis  74  •  Pitfalls in Debridement  74 
•  Other Methods of Debridement  75
9. Dressings and Topical Agents in Wound Care..........................................................................................79
Mohit Sharma, Deepak Balasubramanian
•  Wound Healing  79  •  Classification of Wounds in Relation to Wound Closure  80  •  Rationale behind
Wound Dressings  80  •  Classification of Wound Dressings  81  •  Topical Agents in Wound Healing  82

Principles and Practice of Wound Care
xvi
10. Surgical Closure of Wounds.......................................................................................................................86
VK Tiwari, Anshumali Mishra
•  Techniques of Wound Closure  86  •  Suturing Technique  87  •  Suturing Needles  90  •  Sutures  91 
•  Newer Wound Closure Techniques   91  •  Skin Grafting  92
11. Surgical Site Infection: Preventive Strategies...........................................................................................98
Vinod K Malik, Ashish Dey
•  Classification of Surgical Wounds  98  •  Definition of SSI  98  •  Epidemiology and Microbiology  99 
•  Reducing the Risk of Surgical Site Infections  99
12. Fungal Wound Infections: ­Diagnosis and Management.........................................................................102
Malini Capoor
•  Epidemiology  102  •  Pathogenesis including Risk ­Factors  103  •  Clinical Features of Fungal ­Surgical
Site Infections (SSIs)  104  •  Diagnosis  104  •  Management  107
Section 3: Types of Wounds and their Management
13. Crush Injuries of Limbs.............................................................................................................................113
S Raja Sabapathy, Praveen Bhardwaj
•  Crush Syndrome in Limb Injuries  113  •  Wound Management in Crush ­Injuries of the Limbs  120
14. Skin Avulsion Injuries................................................................................................................................122
Arun Goel
•  Types of Avulsion Injuries   123  •  Mechanism of Production of Avulsion Injury  124  •  Clinical Features  126 
•  Management  127  •  Avulsion Injury of Specialized Structures  135  •  Some Other Avulsions  150 
•  Outcome of Avulsion Injuries: Early and Late  150
15. Medical Management of Diabetic Ulcer....................................................................................................154
PG Raman
•  Genesis of Diabetic Foot Ulcer  154  •  Impaired Wound Healing and Infection in Diabetes Mellitus  155 
•  Laboratory Investigation  156  •  Economics of Treatment of Diabetic Foot  156  •  Management  156 
•  Charcot Foot  158
16. Diabetic Foot Infections.............................................................................................................................160
TD Chugh, Ashish Kumar Duggal, Shalini Duggal
•  Pathophysiology of Infection  160  •  Microbiology  161  •  Assessing Severity of Infection  163 
•  Bone Infection Associated with Diabetic Foot  164  •  Treatment  164
17. Surgical Management of Diabetic Foot....................................................................................................169
Imran Ahmed
•  Classification of Diabetic Foot Ulcer  169  •  Anatomic Location of Foot Ulcers  170  •  Causes of Foot Ulcers
in ­Diabetics  170  •  Assessment  171  •  Investigation  171  •  Management  171  •  Rehabilitations  180
18. Recent Advances in Management of Chronic Non-healing Diabetic Foot Ulcers................................183
Ashok Damir
•  Management of DFU  183  •  Microbiological Control  183  •  Wound Control  184  •  Bioengineered Alternative
Tissues  189  •  Metabolic Control  189  •  Vascular Control  189  •  Mechanical Control—Offloading  189
19. Vascular Ulcers...........................................................................................................................................192
Rajiv Parakh, Anurag Agarwal
•  Definition  192  •  Classification of Leg Ulcers  192  •  Clinical Presentation  193  •  Diagnosis  194 
•  Management of Chronic Leg Ulcers  194  •  Surgery  196
20. Vasculitic Ulcer...........................................................................................................................................199
Rakesh Kain
•  Pathogenesis  199  •  Histopathology  200  •  Classification  201  •  Clinical Manifestation   201 
•  Management  205

Contents 
xvii
21. Healing and Management of Burn Wound...............................................................................................208
Sujata Sarabahi, VK Tiwari
•  Burn Wound Classification  208  •  Pathology of Burn Wound Healing  212  •  Aims of Burn Wound Care  214 
•  Management  215
22. Management of Radiation Wounds...........................................................................................................235
Sandeep Mehta
•  History  235  •  What is Radiotherapy?  236  •  Methods of Delivery  237  •  Radiation Injury—
Biological Effects  238  •  Pathophysiology of the Response to Radiation Injury  240  •  Treatment of
Radiation-induced Wounds  245  •  Radiation Ulcers  246  •  Osteoradionecrosis  257  •  Current Treatment
Strategies  264  •  Future Treatment Modalities  265
23. Management of Trophic Ulcer on Feet.....................................................................................................274
Atul Shah
•  Pathogenesis and Risk Factors  274  •  Clinical Features  275  •  Clinical Evaluation  276  •  Management  276 
•  Surgical Management  277
24. Pressure Sores...........................................................................................................................................283
Arun Goel
•  History  284  •  Etiopathogenesis  284  •  Prevention  288  •  Laboratory Studies  291  •  Treatment  291
25. Orthopedic Device Related Infections......................................................................................................299
Sumit Batra, Sumit Arora
•  Microbiology of Implant Infection  299  •  Pathophysiology of Implant Infections  300  •  Presentation  301 
•  Prevention and Management  301
26. Necrotizing Fasciitis: An Overview...........................................................................................................304
Chintamani, Rohan Khandelwal, Megha Tandon
•  Classification  305  •  Microbiology  305  •  Pathology  305  •  Clinical Features  306  •  Diagnosis  308 
•  Management  309  •  Supportive Treatment  310  •  Prognosis  311  •  Fournier’s Gangrene  311 
•  Clostridial Cellulitis and Myonecrosis  312  •  Non-clostridial Anaerobic Cellulitis  312
27. Bite Wounds...............................................................................................................................................315
Deepak Nanda, Thakur Thussu
•  Epidemiology  315  •  Pathophysiology  315  •  Clinical Manifestations  316  •  Management  316 
•  Complications  319  •  Human Bites  319
28. Malignant Wounds.....................................................................................................................................322
Chintamani, Megha Tandon, Rohan Khandelwal
•  Incidence  322  •  Impact on Quality of Life  322  •  Etiopathogenesis  323  •  Wound Malodors  324 
•  Symptoms  327  •  Diagnosis of Malignant Wounds  328  •  Management of Malignant Wounds  328
29. Chemo-Extravasation: Medical and Surgical Management...................................................................336
Sandeep Mehta, Himesh Gupta
•  Vesicants  337  •  Irritants  338  •  Risk Factors  338  •  General Considerations in Chemotherapy ­Extravasation—
Initial Management  339  •  Surgical Management ­Considerations  342
30. Gunshot Wounds........................................................................................................................................348
Deepak Nanda, Thakur Thussu
•  History of Ballistic Injury  348  •  Pathophysiology  348  •  Wounding Mechanism  349  •  Management  350
31. Reconstructive Modalities of Non-healing Wounds of Lower Limb......................................................352
V Bhattacharya, PS Barooah, S Bhattacharya, NK Agrawal
•  Vascular Basis of Reconstruction  352  •  Surgical Modalities  353  •  Flap Selection  353 
•  Preoperative Evaluation  353  •  Flap Planning  354  •  Postoperative Care  360

Principles and Practice of Wound Care
xviii
32. Foot Defects................................................................................................................................................364
Sameek Bhattacharya, Ashish Rai
•  Surgical Anatomy  364  •  Reconstruction of Foot Defects  365  •  Sensory Recovery of Sole after ­Reconstruction  372
33. Management of Upper Extremity Wounds...............................................................................................374
Durga Karki
•  Etiology  374  •  Management  376  •  Reconstruction of the Wound  377  •  Postoperative Care  383
34. Issues in Neonatal Wound ­Management..................................................................................................387
Harish Chellani, Pratima Anand
•  Types of Wounds  388  •  Guidance and Recommendations for Prevention of Neonatal Wounds  393  •  Best Practice
at Dressing Changes  395  •  Pain Assessment and Management  396  •  Communication with Parents  397 
•  Documentation  397
Section 4: Miscellaneous
35. Role of Regulated Negative ­Pressure Therapy in Wound Healing........................................................401
Moris Topaz
•  The Physical Basis of RNPT  402  •  Clinical Applications of RNPT and RO-NPT  408  •  Suction Forces
and Acute Bleeding  409  •  Clinical Applications of RNPT and RO-NPT—Case Presentations  412
36. Role of Nutrition in Wound Healing..........................................................................................................432
Karoon Agrawal
•  Normal Nutritional Requirements  432  •  Nutritional Assessment  433  •  Pathophysiology of Wound Healing  435 
•  Role of Nutrients in Wound Healing  436
37. Role of Physiotherapy in Wound Healing................................................................................................447
Ram Shanmugam
•  An Overview on Role of ­Physiotherapist in Wound ­Healing  448  •  Role of Exercise Therapy in Wound Healing  448 
•  Role of Electrical Stimulation in Wound Healing  448  •  Role of Ultrasonic Therapy in Wound Healing  452 
•  Ultraviolet Therapy in Wound Healing  453  •  Laser Therapy in Wound Healing  454  •  Role of Hydrotherapy
in Wound Healing  455
38. Hyperbaric Oxygen Therapy in Management of Wounds.......................................................................457
Ashish Rai, Sameek Bhattacharya
•  Introduction and Definition of Hyperbaric Oxygen  457  •  History  457  •  Mechanism of Oxygen Transport in
Hyperbaric Oxygen Therapy  457  •  Role of Oxygen in Wound Healing  458  •  Therapeutic Effects of Hyperbaric
Oxygen  458  •  Hyperbaric Oxygen Therapy Protocol  459  •  Hyperbaric Oxygen Therapy in Wounds  459 
•  Side Effect and Complications  461
Index .....................................................................................................................................................................463

History and Healing
1
Section

(Trang không có chữ)

Introduction
Management of wounds is an art as old as humanity. There is
vivid evidence of trauma and its consequences from various
archaeological finds (Figure 1). Since time began the human
body has had to deal with open wounds due to injuries or
diseases. Pressure sores have been discovered on 5,000 year
old mummies in Egypt. Whenever an individual develops an
open wound, nature attempts to cover the wound to prevent
infection by the growth and migration of epithelial cells (the
first layer of skin). Life forms evolved from a single cell to
amphibians and finally mammals, the pristine ability to heal
by regeneration was lost and thus repair by inflammation and
subsequent deposition of matrix protein (scar) evolved as the
method of mammalian healing. This evolutionary change
leading to scar (the deposition of collagen) seems to be the
key to preventing regeneration. It is well-known that when the
point is reached on the ladder where regeneration no longer
occurs, wound repair occurs by inflammation and collagen
deposition. In fact, if one takes a form of life, which seems
the first link between regeneration and scar formation and
a collagen crosslinking inhibitor is fed to the animal, then
probably regeneration will once again occur! If we could only
bridge this gap, imagine how successful we could become
in the management of chronic wounds. Although uncertain
regarding why this occurred in the evolutionary process,
it is hypothesized that as mammals became sophisticated,
• Ancient Medical Practice (460–136 BC)
• Middle Ages (476 AD–1453)

– Early Middle Ages

– Late Middle Ages and Renaissance
• Modern Ages

– The 17th, 18th and Early 19th Centuries

– The 19th and Early 20th Century

– Late 20th Century (1950s Onward)
• Recent Advances in Wound Coverage
they needed rapid healing to protect themselves from other
predators and for survival in a very hostile environment.

Wound care evolved from ancient medical practice (Greek
medical practice 460–136 BC) through middle ages (476 AD–
1453) to modern era of wound care (15th to 20th century)
management.
ANCIENT MEDICAL PRACTICE
(460–136 BC)
The treatment of acute and chronic wounds is an ancient area
of specialization in medical practice, with a long and eventful
clinical history that traces its origins to ancient Egypt and
Greece.

Neanderthal man treated burns wounds with extracts of plants.
The Egyptians used incantations (magic potions), mixture of
gum, goat’s milk, and milk from a woman who have given birth
to a son. Examples of ancient plant remedies are boundless. The
use of bread mould in folk medicine by Chinese to treat small
burns is undoubtedly timeless but dates back in written record to
at least 2000 years.1 They also used tinctures and extracts made
from tea leaves. More recent use of tannic acid would seem
similar, since tea leaves are rich in tannin. In their writings the
Chinese folk practitioners reported extravagant therapeutic results
from “moxibustion” (Acupuncture methodology).2 Alexander
Fleming’s discovery of Penicillin3 may have been known long
before its modern discovery. Similarly, many civilizations had
Savita Arora
Evolution of Wound Care
1
Chapter

History and Healing
Section 1
4
recognized the properties of silver in preventing diseases. For
instance, the Romans used silver nitrate therapeutically, and
the hermetic and alchemical writings of Paracelsus speak of
the virtues of silver as a healing agent. The Smith and Ebers
Papyrus, circa 1500 BC, details the use of lint, animal grease,
and honey as topical treatments for wounds. The lint provided
a fibrous base that promoted wound site closure, the animal
grease provided a barrier to environmental pathogens, and
the honey served as an antibiotic agent.4 Edwin Smith was
an American Egyptologist who bought the papyrus from a
trader in Luxor in 1862.11 The papyrus is dated at around 1500
BC but it is a copy of original manuscripts that date back to
around 3000 to 2500 BC. The Egyptians believed that closing
a wound preserved the soul and prevented the exposure of the
spirit to “infernal beings”, as was noted in the Berlin papyrus.
Papyri nevertheless speak of draining of suppuration from
wounds, yet they antedate Halsted’s aseptic technique for
wound management by several millennia. The sages of Papyri
tell us that it is good for wound to “rot” a bit, planting the
seeds in the middle ages and the renaissance of the dictum
of “laudable pus.” They believed pus to be helpful so long
as it was not excessive.3 The doctrine stated in Latin, “Pus
bonum et laudible” remained until it was finally condemned
3000 years later in the works of the French surgeon Ambroise
Pare. The Greeks, who had a similar perspective on the
importance of wound closure, were the first to differentiate
between acute and chronic wounds, calling them “fresh” and
“non-healing”, respectively. Galen of Pergamum, a Greek
surgeon who served Roman gladiators circa 120 to 201 AD,
made many contributions to the field of wound care. The
most important was the acknowledgment of the importance of
maintaining wound-site moisture to ensure successful closure
of the wound. For treating head wounds ‘trephination’ also
called ‘trepanation’ that is drilling and removing bone from
the skull was widely reported and accepted in many cultures
including the ancient Egyptian and American Indian.5,6 It has
been reported to have been done as long as 10,000 years ago.

In ancient Rome, there were apparently three methods in
use: (a) Celsus described treatment with mixture of honey and
bran and later, cork and ashes; (b) Pliny the Elder advised the
exposure method for treating burns instead of using ointments
and covering the wounds; and (c) Galen suggested vinegar
and wine.

In early recorded history (1000 BC), the Egyptians repaired
wounds with primitive suture materials (such as insect claws)
across wounds to allow approximation (Figure 2). To apply
a suture, an individual ant was so placed that its jaws, which
were widely open, close upon the edges of the skin and draw
them firmly together. The head was then cut off, and the jaws
remained firmly attached until the wound healed.

As the power of ancient Egypt waned, the Greek civilization
gradually developed. Among the men who made the mark at
this time was Hippocrates.

Hippocrates and Herophilus are the two distinguished
thinkers and philosophers of the classical period of Greek
medical practice.7

Hippocrates (circa 460–370 BC)8,9 is known as Greek God
of Medicine who gave us much of our ethical and scientific
heritage (Figure 3). He is a role model physician for all times.
Figure 2: Ancient method of suturing wound by insect claws
Figure 1: Cartoon figure representing the evolution of wound care
ellicited from the ancient scriptures

Evolution of Wound Care 
Chapter 1
5

Hippocrates—Greek God of Medicine,

Spurred the Greek tradition of dry healing

Felt that a dry environment was closer to the condition of
normal tissue

For an obstinate ulcer, sweet wine and a lot of patience
should be enough….

Hippocrates is believed to have been born on the Greek
island of cos, where he headed a Greek school of medicine.

The teachings of Hippocrates give us fundamental tips
in treatment of wounds. He emphasized that the physician
should use good light and should be comfortable when
examining a patient, and importantly, that the injured part or
site should be compared to the corresponding uninjured parts.
He defined healing by first intention, where skin edges are
held in approximation to each other, and secondary intention
where there is tissue loss and skin edges are far apart.

He used clean sheets on surgical fields to prevent
“suppuration.” The Greeks, led by Hippocrates, devised
methods of treatment for primary wounds and chronic wounds.

They preferred dry wound and avoided greasy ointments
and believed that rest and immobilization is better than
bandages and splints (Figure 4).

They used various materials empirically which included
wine, milk, honey, and other substances in open wounds
similar to our treatment today. Today, one can assign scientific
rationale to some of these ancient empirical choices. For
example, the complex sugars of honey are known to suppress
the growth of gram-positive bacteria and because of its
antibacterial properties it was used as topical ointment in
infected wounds. For about 4000 years, honey has been a
popular folk remedy around the world for ailments ranging
from diarrhea to inflammation of the eyelids. Ancient Egyptians
described it as an effective treatment for wounds and modern
studies have verified honey’s superiority to standard medical
treatment of burns, skin ulcers and wounds. Wine suppresses
Pseudomonas proliferation. Milk products may contain
cytokines or serve as buffers to control wound pH. Although
the ancients had no idea that pus was actually made up of
proteins and dead leukocytes, they understood that drainage
of localized products of infection was a good sign (laudable
pus). They understood that when signs of inflammation could
not be localized, death would inevitably follow. During
the early Roman era, Celsius, unaware of the existence of
bacteria, did recognize and describe the cardinal signs of
clinical infection being: (A) rubor—erythema, (B) tumor—
swelling, (C) dolor—pain, and (D) calor—heat.

Grande Chirurgie written by de Chauliac describes the use
of tents (drains) and meshes (packing) to hold wounds open
and oily salves to promote pus formation and de Chauliac’s
book was the primary surgical textbook for 200 years.12

Herophilus of Chalcedin—Bythnia (circa 335–280 BC) was
the grandson of Aristotle and was educated by Praxagorus.9
Herophilus founded the great school of Anatomy at Alexandria.
He was known as the “father of anatomy”. His contribution was
mainly on Head Wounds and their Healing. He also became
the first medical obstetrician recorded in western history. He
practiced human vivisection.9

In 1600s AD, wound care focused on maintaining a dry
wound environment. Dressings such as cotton linters, paper,
feathers, and dust were used.
Figure 3: Hippocrates—Greek God of Medicine
Figure 4: Ancient Greeks believed in keeping the wounds dry

History and Healing
Section 1
6

Sushruta, an Indian surgeon lived sometime between the
sixth century BC and the sixth century AD (Figure 5). His
surgical textbook, the Sushruta Samhita10 gives examples of
ancient Indian surgical technique and wound management.
Sushruta described 14 different types of dressings made from
silk, linen wool and cotton. He also placed great emphasis on
the importance of cleanliness.11 He gave recommendations
for the management of intestinal wounds. First black ants
were applied and then he washed the intestines with milk
and lubricated with butter and then returned them to their
normal position. He differed from Hippocrates on the most
appropriate diet for patients. Sushruta considered meat,
normally forbidden to Hindus, an important factor whereas
Hippocrates recommended the restriction of food and gave
his patients only water to drink. Two surviving examples of
ancient Indian surgical teaching and wound care are cited as
illustrative.10 On rhino plastic operations:

Now I shall with the process of affixing an artificial nose.
First the leaf of a creeper, long and broad enough to cover
the whole of the severed (nose) is clipped off. Part should be
gathered, and a patch of living flesh equal in dimension to
the preceding leaf should be sliced off (from down upward)
from the region of the cheek and after sacrificing it with a
knife, swiftly adhered to the severed nose. Then the cool
headed physician should steadily tie it up with a bandage
decent to look at and perfectly sealed to the end for which it
has been employed (Sadher Vandana)…. The adhesioned part
should be dusted with powders of Pattenya, Yashtimadhiekam,
Rasannjana pulverized together and the nose should be
enveloped in Karpase cotton and several times sprinkled with
the refined oil of pure sesamum.

Regarding an ear that had been lost:

A surgeon well versed in the knowledge of surgery
(Shastras) should slice off a patch of living flesh from the
cheek. Then the part where the artificial ear lobe is to be made
should be slightly scarified (with a knife) and the living flesh
full of blood and sliced off flesh as previously directed should
be adhesioned to it (so as to resemble a natural ear lobe in
shape).

The volumes of his book provide detailed directions on
dieting and postoperative management in addition to extensive
discussions on all manners of disease treatments.
MIDDLE AGES (476 AD–1453)
Early Middle Ages
Arab doctors of Islam developed medical knowledge after
the fall of Roman empire. Conon Medicina was written
by Avicenna which was the foremost medical text till
the seventeenth century.13 With spread of Islam, medical
knowledge swept across Middle East, North Africa and
Europe. Salerno in southern Italy was the leading center
for surgical training in the eleventh century and Surgery of
Roger was written during this time.14 Roger used lard for head
wounds, either applied directly or soaking cloth in molten
lard for deep wounds. He used dressings made from eggs
and water tow and salt and bandages of fine linen cloth. The
famous Arabian physician Rhases, in about ninth century—
representing Arabic thought—recommended the use of cold
water for the alleviation of pain. How modern he was!

Hugo of Lucca (1160–1257) was the expert surgeon who
graduated from Salerno. His famous pupil Theodoric wrote
a surgical textbook Chirurgia. Theodoric disagreed with the
concept of “laudable pus” as he considered that it delayed
healing. He cleansed the wound with wine, debrided it and
removed all foreign matter, approximated the wound edges
using compresses of lint soaked in warm wine and then
binding them in place.15
Late Middle Ages and Renaissance
Kirkpatrick and Naylor have described the contents of
surgical treatise dated 1446 which was the work of Thomas
Morstede (1380–1450) who was an English surgeon. He
gave detailed information about the classification of ulcers
and their treatment. Step by step approach was described to
manage ulcers, the processes of mortification (debridement),
mundification (cleansing) and fleshing (encouragement of
granulation tissue). Recipes for various topical applications
Figure 5: Sushruta—an Indian ancient surgeon

Evolution of Wound Care 
Chapter 1
7
were provided which included sage leaves, wormwood, white
Gasony wine, alum and honey.

Ambroise Pare (1510–1590) was the most famous surgeon
of the renaissance period.11 He was surgeon to four successive
French Kings and got the titles of Premier Chirurgien and
Consieller du Roi. He was a military surgeon. Pare proposed
using dressings composed of rock alum, verdigris, Roman
vitriol, rose honey and vinegar, boiled together to form paste,
on traumatic gunshot wounds. He also advised the treatment
of pressure sores by encouraging the patient, feeding him,
providing pain relief and sleep—inducing medication and
pressure relief by means of a small pillow.
MODERN AGES
The 17th, 18th and Early 19th Centuries
In1800s, Caregivers used cotton gauze, knit fibers, nonwoven,
swabs, sleeve dressings, and adhesive paper . Unclean cotton,
collected from sweepings on the floors of textile mills was
used for surgical dressings; surgeons operated in street clothes
and wore blood-spattered frock coats like a badge of honor.

Lorenz Heister (1683–1758) was the German surgeon of
this era who wrote a General system of surgery in three parts
on the doctrine and the management of: 1. wounds of all kinds,
2. operations, 3. bandages.16 To treat hemorrhagic wounds
he used lint dressings dipped in alcohol or oil of turpentine.
He also suggested that wound edges should not be closed to
allow pus to drain. He believed that all bandages should be
made from clean linen that had been softened by repeated use
(Figure 6).

Spanish Civil War resulted in many medical innovations,
which became critical in the treatment and management of
war wounds in the second World War. The period from the
end of the 19th century to the end of World War II saw radical
developments, innovations, discoveries, and changes in
medical treatment of trauma. Much has been written about the
devastating casualties of World War I and the ways in which
technological innovations—airplanes, mustard gas—resulted
in wounds, casualties, and trauma unknown in previous wars.
A lot has also been written about the medical innovations
coming out of the World War II which have contributed to
the avalanche of medical discoveries of the past 60 years.
However, very little has been written about what was learned
or confirmed during the Spanish Civil War.

One development was that of debridement, possibly
originated by Henri Francois Le Dran (1685–1770) in order
to relieve the constriction on soft tissues followed by gunshot
wounds, few English surgeons disagreed with the concept
but during the Napoleonic wars, several surgeons advocated
the use of debridement, particularly in the care of gunshot
wounds.17 The concept was entirely forgotten after the fall of
Napoleon and his empire.

There were limited advances that continued throughout
the middle ages and the renaissance, but the most profound
advances, both technological and clinical, came with the
development of microbiology and cellular pathology in the
19th century by Rudolf Virchow23 (1821–1902), whose
contributions to microscopic and cellular pathology have
been of immeasurable value . His observations and methods,
following centuries of macroscopic examination, directly led
to the examination and understanding of wound healing at the
cellular level. Skin grafting by Karl Thiersch24 (1822–1895)
revived an ancient art found in Sushrata. Lambert gave the
technical detail of suturing to achieve perfection in 19th
century.
The 19th Century and Early 20th Century
The Crimean war lead to huge demand for dressings. Various
types of dressings were produced in the workhouses. Charpie
was made from unraveled cloth. Oakum was old rope which
had been unpicked and teased into fluff; it became very popular
during American Civil War as it was considered very absorbent.18
Tow was made from broken ravelled flax fibers. Lint is linen that
has been scraped on one side. These dressings were washed and
reused many times so they gradually became quite soft but they
were not very absorbent. Sheets of cotton wool retained by cotton
bandages were used during the Franco-Prussian wars, but Joseph
Sampson Gamgee (1828–1886) was the person who conceived
Figure 6: Florence Nightingale taking care
of wounded patients

History and Healing
Section 1
8
the idea of covering the cotton wool with unbleached gauze to
make dressing pads or Gamgee tissue.19

The discovery of iodine was incidental when Bernard
Courtois in 1811 (1777–1838) while searching to kill his
fellow humans on the contrary found that it helps in healing
wounds.

During the first World War, severely wounded soldiers
had to wait for several days before they could receive simple
field dressing. As a result many wounds became infected
and gangrenous. During American Civil War, erysipelas
(necrotizing infection of soft tissue) and tetanus accounted
for over 17,000 deaths. Bilateral compound fracture at
the time almost invariably were associated with infection,
amputation was the only option despite a 25 to 90 percent risk
of amputation stump infection. To resolve this problem, two
similar antiseptic solutions came into use: eusol (Edinburgh
University Solution of Lime) and Daikin’s solution.
Antiseptics like iodine, carbolic acid, mercury and aluminum
were also in use. Some of the medical literature was reviewed
by Sinclair and Ryan (1993) to identify the thinking on the use
of antiseptics in the nineteenth and twentieth century. Bond
(1915) considered that it was important to apply a ‘germicide’
as early as possible to wounds that were almost certain to be
infected. British soldiers were advised to carry tincture of
iodine so that they could apply it immediately to any gunshot
wounds21 though Herzog reported that soldiers developed
dermatitis of the skin around the wound as a result of the
indiscriminate use of iodine.

Desparge, a Belgian surgeon felt that antiseptics in the war
wounds were not sufficient enough and he revived the concept
of wound debridement17 which involved exploring the wound
with excision of all contused contaminated and dead tissue.
Wounds were kept open and irrigated with Dakin’s solution.
His concept of wound debridement had a major impact on
trauma surgery during 19th and 20th century.

The first advances in wound care in this era began with
the work of Ignaz Philipp Semmelweis25 (1818–1865) a
Hungarian obstetrician and Louis Pasteur, a French scientist
known as the “father of microbiology” for his germ theory
of disease who developed sterile surgical procedures after
he observed high incidence of lethal puerperal sepsis (child
bed fever) that occurred when physicians did not wash their
hands when coming from an autopsy to deliver a child.
Semmelweis’s work was furthered by an English surgeon,
Joseph Lister, who began treating his surgical gauze with
carbolic acid, known today as phenol, and subsequently
dropped his surgical team’s mortality rate by 45 percent.
Building on the success of Lister’s pretreated surgical gauze,
Robert Wood Johnson, co-founder of Johnson and Johnson,
began producing gauze and wound dressings treated with
iodine.20 These innovations in wound-site dressings marked
the first major steps forward in the field since the advances
of the Egyptians and Greeks centuries earlier. The next few
advances arose from the development of polymer synthetics
for wound dressings and the “rediscovery” of moist wound-
site care protocols in the mid 20th century.

A wide variety of pharmaceutical preparations were
introduced and were in use during this time without any
evidence-based care. The British Pharmaceutical Codex was
published in 1907 which contained information on all the
drugs and medicinal preparations which are quiet similar to
more recent list of dressings in the British Pharmacopoeia.

It was only during last 30 years that attempt has been made
to design materials that are actually functional.22
Late 20th Century (1950s Onward)
With advancements in material and tissue sciences, the field
of wound-site dressings advanced considerably. The ability to
bolster wound-site re-epithelialization has been improved as
well as improving their clinical efficacy. With the advent of
fibrous synthetics of nylon, polyethylene, polypropylene, and
polyvinyl in the 1950s, researchers and doctors in the field
of wound care are able to significantly accelerate the natural
wound healing process. Following the research and articles
of George Winter and Howard Maibach in the 1960s, testing
the efficacy of synthetic “wet” polymer wound dressings,
the 1970s and 1980s represented the dawn of modern wound
care treatment. In the 1990s, improvements in composite and
hybrid polymers expanded the number of available materials
for wound dressings. These improvements, coupled with the
developments in tissue engineering, have given rise to a new
class of wound dressings called “living skin equivalents”.
Often cited as a misnomer because they lack key components
of whole living skin, “living skin equivalents” represent the
future of wound dressings and possess the potential to serve
as cellular platforms for the release of growth factors essential
for proper wound healing. Other new developments have been
focusing on handling patients concerns. Affected individuals
often report pain as dominant in their lives and the pain
associated with chronic wounds should be handled as one of
the main management priorities. Symptomatic treatment of
pain as part of patient centered concerns must go hand-in-hand
with treating the underlying etiology or cause of the wound.

During 1998, many types of dressings were devised like
tulle grass, a gauge impregnated with paraffin by Lumiere.
Sphagnum moss was also used as an absorbent dressing.
Eupad a Eusol preparation was designed for use in leg ulcers.

Evolution of Wound Care 
Chapter 1
9
Recent Advances in Wound
­Coverage
A new generation of sophisticated products entering the
21st century market should finally put to rest the notion that
purchasing wound care products is little more than ordering
gauze. To the contrary, wound care represents a new frontier
for product development as decubitus pressure ulcers, venous
leg ulcers and diabetic foot ulcers are seen more frequently.

During its recent evolution, advanced wound care has
become the preferred environment for product innovation.
In recent years, manufacturers have introduced a scores of
advanced wound care products, including alginate and foam
dressings; antimicrobial and odor-control dressings; film and
hydro colloid dressings; hydrogel and non-adherent dressings;
negative pressure therapy; wound-preventing support surfaces;
non occlusive and semi-occlusive dressings; topical wound
analgesics and antibiotic formulations; wound cleansers and
chemical/enzymatic wound debriders, biocompatible and
tissue engineered skin grail products (skin substitutes); which
can be synthetic or biological; temporary or permanent, e.g.
integra and dermagraft are permanent synthetic dermal skin
substitutes, alloderm is biological dermal skin substitute,
cultured keratinocytes are epidermal skin substitutes. These
may hold the future for extensive wound coverage. Temporary
skin substitutes like collagen are available in different forms
(dry or wet). Creams with growth factors (epidermal or platelet
derived) are available by the name of Epigraf and Plermin.
These bind to epidermal growth factor (EGF) receptor,
tyrosine kinase mechanism gets activated which leads to
DNA and protein synthesis which leads to cell proliferation.
New pathways receptors, cell populations, drugs and new
interventions are currently being investigated to change the
immunocompromised patient into an immune competent
patient to improve wound healing and survival.

Gene therapy is a new approach in wound healing. Non-
viral constructs have been shown to effectively change the cells
into a productive and active cell that releases growth factors to
improve dermal and epidermal regeneration. Extensive research
is also being carried out in fat derived or bone marrow derived
stem cell for wound healing. This is still in experimental stage.

More details recent advances in wound care products are
given in other chapters in this book and the reader is advised
to refer to them also.
SUMMARY
Since time began the human body has had to deal with open
wounds due to injuries and diseases.Wound care evolved
from ancient medical practice (460–136 BC) through middle
ages (476–1453) to modern era of wound care (15th to 21st
century). Today, our aim is closure of wound as early as
possible to prevent wound infection and other complications
of open wounds. Papyrus an ancient manuscript details
about wound management of ancient period. Today one can
assign scientific rationale to some of these ancient empirical
choices. ‘Sushruta Samhita’ a surgical textbook by Sushrata
an ancient Indian surgeon gives examples of ancient Indian
surgical technique and wound management. After the fall of
Roman empire it was the Arabs who popularized the medical
knowledge across the Middle East, North Africa and Europe.
Leading centers for surgical training were set during this time,
also many textbook of surgery were written like Surgery of
Roger, Chirurgia by Theodoric. War injuries resulted in
medical innovations especially various types of dressings and
antiseptic solutions.

Some of the most profound advances of 19th century were
the development of microbiology and cellular pathology by
Rudolf Virchow’s (1821–1902) and Louis Pasteur (known
as father of microbiology) with his ‘germ theory of disease’
which led to the development of sterile surgical techniques.
Building on the success of Lister’s pretreated surgical gauge,
Robert wood Johnson, co-founder of Johnson and Johnson
began producing gauge and the wound dressings treated with
iodine. These innovations in wound site dressings marked the
first major steps forward in the field since the advances of the
Egyptians and the Greeks centuries earlier.

The next few advances arose from the development of
polymer synthetics for wound dressings and the “rediscovery’’
of moist wound site protocols in mid 20th century which
significantly accelerated the natural wound healing process.
In 1990s improvements in composite and hybrid polymers
along with development in tissue engineering have given
rise to new class of wound dressings called “living skin
equivalents” which represents the future of wound dressings.
A new generation of sophisticated products entered the 21st
century market like alginate and foam dressings, hydrocolloid
and hydrogel dressings to skin substitutes like integra® and
dermagraft®. Cultured keratinocytes are epidermal skin
substitutes–they may hold the future for extensive wound
coverage.
References
1. Lecture in, Chinese traditional medicine. Gangzhou (Canton),
China Zuong Cho School of Chinese Traditional medicine,
May 1984.
2. Yihuangk Jai W. An introduction to the study of Moxibustion
in China. J Traditional Chin Med. 1985;5:67-76.
3. Fleming A. Streptococcal meningitis treated with Penicillin.
Lancet. 1943;2:434-8.

History and Healing
Section 1
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4. Peter Charles Molan. ‘Honey as a topical antibacterial agent for
treatment of infected wounds’. Nurse Times. 2001;49(7-8):96.
5. Majno G. The Healing Hand: Man and wound in the Ancient
world. Cambridge, MA, Harvard University Press, 1975.
6. Steinbock RT. Paleopathological Diagnosis and interpretation
(Bone Diseases in Ancient Human populations). Springfield IL
Charles Thomas 1976.
7. Garrison FH. An Introduction to the History of Medicine.
Philadelphia, WB Saunders 1929;92-101.
8. The Genuine Works of Hippocrates. Trans F Adams, London
1849.
9. Gordon BL. Medicine Thought Antiquity. Philadelphia, FA
Davis. 1949. pp. 548, 594-8.
10. Sushrata Samhita Vol. 1 to 3 Trans KK Bhishagratna Varanasi,
India, Chowkhambra Sanskrit.
11. Zimmerman LM, Veith I. Great Ideas in the History of Surgery.
Williams and Wilkins, Baltimore, MD, 1961.
12. Johnson PC. Guy de Chauliac and the Grand Surgery. Surgery,
Gynaecology and Obstetrics. 1989;169:172-6.
13. Dealey C. Wound healing in Moorish Spain. EWMA Journal.
2002;2(1):32-4.
14. Paterson LM. Military surgery: knights, sergeants and Ramon
of Avignon’s version of Chirurgia of Roger of Salerno. In:
Harper-Bus C, Harvey R, (Eds). The Ideals and Practice of
Medieval Knighthood. The Bodell Press, Woodbridge, Suffork.
Popp AJ. Crossroads at Salerno: Elderidge Campbell and the
writings of Teodorico Borgognoni on wound Healing. Journal
on Neurosurgery 1988.1995;83:174-9.
15. Borgognoni T. The Surgery of Theodori. Translated from the
Latin by Campbell E, Colton J Appleton-Crofts, and New
York. 1955;(1).
16. Heister L. A General System of Surgery in Three Parts, 6th
edn. Translated into English by Heister L Whiston, London,
1768.
17. Helling TS, Daon E. In: Flanders Fields: the Great War, Antoine
Deparge and the resurgence of debridement. Annals of Surgery
1998;228(2):173-81.
18. Bishop WJ. A History of Surgical Dressings. Robinsons and
Sons Ltd, Chesterfield, 1955.
19. Lawerence JC. A Century after Gamgee. Burns. 1987;13(1):77-
9.
20. Johnson PC. Wound care, packing cavity wounds. Nursing
Times. 1987;83(36):59-62.
21. Mayo-Robson AW. Hints on war Surgery. British Journal of
Dermatology, 1915. p.136.
22. Turner TD. Recent advances in wound management products,
In: Turner TD, Schmidt RJ, Harding KG, (Eds) Advances in
Wound Management. John Wiley, Chichester 1986.
23. Virchow RLK. Cellular Pathology as based upon Physiological
and Pathological Histology. Trans F Chance. London, John
Churchill 1860.
24. Orr TG. Operations of General Surgery Philadelphia. WB
Saunders; 1944. p. 55.
25. Semmelweis IF. The Etiology, the Concept and the Prophylaxis
of Childhood Fever. Trans FF Murphy. Medical Classics,
Huntington NY, RH Krieger Publishing Co. 1941;5(5).

• Wound Healing
• Phases of Wound Healing

– Inflammatory Phase

– Proliferative Phase

– Maturation Phase
• Types of Wound Healing
• Factors Influencing Healing
• Complications of Wound Healing
• New Horizons
INTRODUCTION
Wounds and their management are fundamental to the
practice of surgery. The concerns revolve around optimizing
wound healing, preventing wound infection and limiting
patient morbidity when managing wound complications.
Understanding the pathophysiology of wound can help
the surgeon in better patient management and improve the
outcomes.
WOUND HEALING
Healing is the body response to injury in an attempt to restore
normal structure and function.

Healing primarily involves two distinct processes:
• Regeneration when healing takes place by proliferation
of parenchymal cells and usually results in complete
restoration of the original tissues.
• Repair when healing takes place by proliferation of
connective tissue elements resulting in fibrosis and
scarring.
PHASES OF WOUND HEALING
There are some differences between healing of different types
of wounds; however the basic mechanisms are similar. The
wound healing process can be divided into three phases:
• Inflammatory (reactive) phase
• Proliferative (reparative) phase
• Maturation (remodeling) phase.

Wound healing is a dynamic process and all the three
phases may occur simultaneously.
Inflammatory Phase
This is the immediate response to injury to rapidly achieve a
sterile environment. The body’s defenses are aimed at limiting
the amount of damage by stopping bleeding, sealing the
surface of the wound and preventing further injury. It involves
hemostasis and inflammation.

The sequence of events can be discussed under the
following headings:
• Vascular events
• Cellular events.
Vascular Events
Alteration in the microvasculature (arterioles, capillaries and
venules) is the earliest response to tissue injury. The sequence
of these changes is as under:
1. Irrespective of the type of injury, immediate vascular res­
ponse is of transient vasoconstriction of arterioles. With
mild form of injury, the blood flow may be re-established
in 3 to 5 seconds while with more severe injury the
vasoconstriction may last for about 5 minutes.
Harsh Mohan, Irneet Mundi
Pathology of Wound
Healing
2
Chapter

History and Healing
Section 1
12
2. Next follows persistent progressive vasodilatation which
involves mainly the arterioles, but to a lesser extent, affects
other components of the microcirculation like venules and
capillaries. This change is obvious within half an hour of
injury. Vasodilatation results in increased blood volume
in microvascular bed of the area, which is responsible for
redness and warmth at the site of acute inflammation.
3. Progressive vasodilatation, in turn, may elevate the local
hydrostatic pressure resulting in transudation of fluid into
the extracellular space. This is responsible for swelling at
the local site of acute inflammation.
4. Slowing or stasis of microcirculation follows which causes
increased concentration of red cells, and thus, raised blood
viscosity.
5. Platelets adhere to exposed subendothelial collagen leading
to platelet aggregation and activation of coagulation
pathway. This leads to clot formation on the surface of
wound. The clot serves to stop bleeding, seals the wound
against dehydration and infection and also acts as a scaffold
for migrating cells.
Cellular Events
The cellular phase of inflammation consists of two processes:
1. Exudation of leukocytes
2. Phagocytosis.
Exudation of leukocytes: The escape of leukocytes from the
lumen of micro­vascu­lature to the interstitial tissue is the most
important feature of inflammatory response. In acute inflam­
ma­tion, polymorphonuclear neutrophils (PMNs) comprise
the first line of body defense, followed later by mono­cytes
and macrophages. The acute inflammatory response occurs
within 24 hours with appearance of polymorphs from the
mar­gins of incision. By 3rd day, polymorphs are replaced by
macrophages.

The changes leading to migration of leukocytes are as
follows:
1. Changes in the formed elements of blood: In the early stage
of inflammation, the rate of flow of blood is increased due
to vasodilatation. But subse­quently, there is slowing or
stasis of bloodstream. With stasis, changes in the normal
axial flow of blood in the microcirculation take place.
The normal axial flow consists of central stream of cells
comprised by leuko­cytes and RBCs and peripheral cell-
free layer of plasma close to vessel wall (Figure 1A). Due
to slowing and stasis, the central stream of cells widens
and peri­pheral plasma zone becomes narrower because of
loss of plasma by exudation. This phenomenon is known as
margination. As a result of this redistribution, the neutro­
phils of the central column come close to the vessel wall;
this is known as pavementing (Figure 1B).
2. Rolling and adhesion: Peripherally margi­nated and
pavemented neutrophils slowly roll over the endothelial
cells lining the vessel wall (rolling phase) (Figure 1C). This
is followed by the transient bond between the leukocytes
and endothelial cells becoming firmer (adhesion phase).
The following molecules bring about rolling and adhesion
phases:

i. Selectins are expressed on the surface of activated
endothelial cells which recognize specific carbo-
hydrate groups found on the surface of neutrophils, the
most important of which is s-Lewis X molecule. While
P-selectin (preformed and stored in endothelial cells and
platelets) in involved in rolling, E-selectin (synthesized
by cytokine-activated endothelial cells) is associated
with both rolling and adhesion; L-selectin (expressed
on the surface of lymphocytes and neutrophils) is
responsible for homing of circulating lymphocytes to
the endothelial cells in lymph nodes.

ii. Integrins on the endothelial cell surface are
activated during the process of loose and transient
adhesions between endothelial cells and leukocytes.
At the same time, the receptors for integrins on the
neutrophils are also stimulated. This process brings
about firm adhesion between leukocyte and endo­
thelium.

iii. Immunoglobulin gene superfamily adhesion
molecule such as intercellular adhesion molecule-1
(ICAM-1) and vascular cell adhesion molecule-1
(VCAM-1) allow a tighter adhesion and stabilize
the interaction between leukocytes and endothelial
cells. Platelet-endothelial cell adhesion molecule-1
(PECAM-1) or CD31 may also be involved in
leukocyte migration from the endothelial surface.
3. Emigration: After sticking of neutrophils to endo­
thelium, the former move along the endothelial surface
till a suitable site between the endothelial cells is found
where the neutrophils throw out cytoplasmic pseu­do­
pods. Subsequently, the neutrophils lodged between
the endothelial cells and basement membrane cross the
basement membrane by damaging it locally with secreted
collagenases and escape out into the extravascular space;
this is known as emigration (Figure 1D). The damaged
basement membrane is repaired almost immediately. As
already mentioned, neutrophils are the dominant cells
in acute inflammatory exudate in the first 24 hours, and
monocyte-macrophages appear in the next 24 to 48 hours.
However, neutrophils are short-lived (24–48 hours) while
monocyte-macrophages survive much longer.


Simultaneous to emigration of leukocytes, escape of
red cells through gaps between the endothelial cells, dia­
pedesis, takes place. It is a passive phenomenon—RBCs
being forced out either by raised hydrostatic pressure

Pathology of Wound Healing 
Chapter 2
13
or may escape through the endothelial defects left after
emigra­tion of leukocytes. Diapedesis gives hemorrhagic
appearance to the inflammatory exudate.
4. Chemotaxis: The chemotactic factor-mediated trans-
migration of leukocytes after crossing several barriers
(endothelium, basement membrane, perivascular myo­
fibroblasts and matrix) to reach the interstitial tissues
is called chemotaxis. The concept of chemotaxis is well
illustrated by Boyden’s chamber experiment. In this, a
millipore filter (3 mm pore size) separates the suspension
of leukocytes from the test solution in tissue culture
chamber. If the test solution contains chemotactic agent,
the leukocytes migrate through the pores of filter towards
the chemotactic agent (Figures 2A and B).

The following agents act as potent chemotactic substances
or chemokines for neutophils:

i. Leukotriene B4 (LT-B4), a product of lipooxygenase
pathway of arachidonic acid metabolites.
ii. Components of complement system (C5a and C3a in
particular).
iii. Cytokines (Interleukins, in particular IL-8).
iv. Soluble bacterial products (such as formylated peptides).

In addition to neutrophils, other inflammatory cells too
respond and partake in inflammation and there are chemokines
for them, e.g. monocyte chemoattractant protein (MCP-1),
eotaxin chemotactic for eosinophils, NK cells for recognizing
virally infected cells, etc.
Phagocytosis: Phagocytosis is defined as the process of
engulfment of solid particulate material by the cells (cell-
eating). The cells performing this function are called
phagocytes. There are two main types of phagocytic cells:

i. Polymorphonuclear neutrophils (PMNs) which appear
early in acute inflammatory response, sometimes called
as microphages.
ii. Circulating monocytes and fixed tissue mononuclear
phagocytes, commonly called as macrophages.
Figures 1A to D: Sequence of changes in the exudation of leukocytes. (A) Normal axial flow of blood with central column of cells and peripheral
zone of cell-free plasma; (B) Margination and pavementing of neutrophils with narrow plasmatic zone; (C) Adhesion of neutrophils to endothelial
cells with pseudopods in the intercellular junctions; (D) Emigration of neutrophils and diapedesis with damaged basement membrane
Figures 2A and B: The Boyden’s chamber with millipore filter, shown
by dotted line. (A) Suspension of leukocytes above is separated from
test solution below; (B) Lower half of chamber shows migration of
neutrophils towards chemotactic agent
A
B
C
D
A
B

History and Healing
Section 1
14

Neutrophils and macrophages on reaching the tissue spaces
produce several proteolyitc enzymes—lysozyme, protease,
collagenase, elastase, lipase, proteinase, gelatinase, and acid
hydrolases. These enzymes degrade collagen and extracellular
matrix.
Proliferative Phase
During this phase, an attempt is made to close the wound and
restore the epithelial barrier. It is characterized by granulation
tissue formation, proliferation and migration of connective
tissue cells and re-epithelization of the wound surface.
Granulation Tissue Formation
Fibroblasts and vascular endothelial cells proliferate in the
first 24 to 72 hours of the repair process to form a specialized
type of tissue called granulation tissue which is a hallmark
of tissue repair. The term granulation tissue derives its name
from slightly granular and pink appearance of the tissue. Each
granule corresponds histologically to proliferation of new
small blood vessels which are slightly lifted on the surface by
thin covering of fibroblasts and young collagen.

This involves two main processes—angio­genesis or neo­
vascularization, and fibrogenesis:

i. Angiogenesis (neovascularization): Formation of new
blood vessels at the site of injury takes place by proli­
feration of endothelial cells from the margins of severed
blood vessels. Initially, the proliferated endo­thelial cells
are solid buds but within a few hours deve­lop a lumen
and start carrying blood. The newly formed blood
vessels are more leaky, accounting for the edema­tous
appearance of new granulation tissue. Soon, these blood
vessels differentiate into muscular arterioles, thin-
walled venules and true capillaries.


The process of angiogenesis is stimulated with prote­
olytic destruction of basement membrane. Angiogenesis
takes place under the influence of the following factors:

a. Vascular endothelial growth factor (VEGF) elabo­
rated by mesenchymal cells while its receptors are
present in endothelial cells only.

b. Platelet-derived growth factor (PDGF), transforming
growth factor- (TGF-), basic fibroblast growth factor
(bFGF) and surface integrins are all associated with
cellular proliferation.
ii. Fibrogenesis: The newly formed blood vessels are
present in an amorphous ground substance or matrix. The
new fibroblasts originate from fibrocytes as well as by
mitotic division of fibroblasts. Some of these fibroblasts
have combination of morphologic and functional
characteristics of smooth muscle cells (myofibroblasts).
Collagen fibrils begin to appear by about 6th day. As
maturation proceeds, more and more of collagen is
formed while the number of active fibroblasts and new
blood vessels decreases. This results in formation of
inactive looking scar known as cicatrisation.
Epithelialization
Re-epithelialization of wounds begins within hours after injury.
Initially the wound is rapidly sealed by clot formation and then
by epidermal cell migration across the defect. Epithelialization
involves a sequence of changes in wound keratinocytes:
detachment, migration, proliferation, differentiation and
stratification. The basal cells of epidermis from both the cut
margins start proliferating and migra­ting towards incisional
space in the form of epithelial spurs. A well-approximated
wound is covered by a layer of epithelium in 48 hours. The
migrated epidermal cells separate the underlying viable dermis
from the overlying necrotic material and clot, forming scab
which is cast off. The basal cells from the margins continue
to divide. By 5th day, a multilayered new epidermis is formed
which is differentiated into superficial and deeper layers.
Extracellular Matrix—Wound Strength
By 3rd day, fibroblasts also invade the wound area. By 5th
day, new collagen fibrils start forming which dominate till
healing is completed. In 4 weeks, the scar tissue with scanty
cellular and vascular elements, a few inflammatory cells and
epithelialised surface is formed. The wound is strengthened
by proliferation of fibro­blasts and myofibroblasts which get
structural support from the extracellular matrix (ECM). In
addition to providing structural support, ECM can direct cell
migration, attachment, differentiation and organisation.

ECM has five main components: collagen, adhesive
glycoproteins, basement membrane, elastic fibres, and
proteoglycans.
1. Collagen: The collagens are a family of proteins which
provide structural support to the multicellular organism.
It is the main component of tissues such as fibrous
tissue, bone, cartilage, valves of heart, cornea, basement
membrane, etc.


Collagen is synthesized and secreted by a complex
biochemical mechanism on ribosomes. The collagen
synthesis is stimulated by various growth factors and is
degraded by collagenase. Regulation of collagen synthesis
and degradation take place by various local and systemic
factors so that the collagen content of normal organs
remains constant. On the other hand, defective regulation
of collagen synthesis leads to hypertrophied scar, fibrosis,
and organ dysfunction.

Pathology of Wound Healing 
Chapter 2
15


Depending upon the biochemical composition, 18 types
of collagen have been identified called collagen type I to
XVIII many of which are unique for specific tissues. Type I
collagen is normally present in the skin, bone and tendons
and accounts for 90 percent of collagen in the body:

• Type I, III and V are true fibrillar collagen which form
the main portion of the connective tissue during healing
of wounds in scars.

• Other types of collagen are non-fibrillar and amorphous
material seen as component of the basement membranes.


Morphologically, the smallest units of collagen are
collagen fibrils, which align together in parallel bundles to
form collagen fibers, and then collagen bundles.
2. Adhesive glycoproteins: Various adhesive glyco­proteins
acting as glue for the ECM and the cells consist of
fibronectin, tenascin (cytotactin) and thrombo­spondin.

i. Fibronectin (nectere = to bind) is the best charac­
terized glycoprotein in ECM and has binding
properties to other cells and ECM. It is of two
types—plasma and tissue fibronectin.

• Plasma fibronectin is synthesized by the liver
cells and is trapped in basement membrane such
as in filtration through the renal glomerulus.

• Tissue fibronectin is formed by fibroblasts, endo­
thelial cells and other mesenchymal cells. It is
respon­sible for the primitive matrix such as in the
fetus, and in wound healing.

ii. Tenascin or cytotactin is the glycoprotein associated
with fibroblasts and appears in wound about 48 hours
after injury. It disappears from mature scar tissue.

iii. Thrombospondin is mainly synthesized by granules
of platelets. It functions as adhesive protein for
keratinocytes and platelets but is inhibitory to
attachment of fibroblasts and endothelial cells.
3. Basement membrane: Basement membranes are periodic
acid-Schiff (PAS)-positive amorphous struc­tures that lie
underneath epithelia of different organs and endothelial
cells. They consist of collagen type IV and laminin.
4. Elastic fibers: While the tensile strength in tissue comes
from collagen, the ability to recoil is provided by elastic
fibres. Elastic fibers consist of 2 compo­nents—elastin
glycoprotein and elastic micro­fibril. Elastases degrade the
elastic tissue, e.g. in inflammation, emphysema, etc.
5. Proteoglycans: These are a group of molecules having 2
components—an essential carbohydrate polymer (called
polysaccharide or glycosaminoglycan), and a protein
bound to it, and hence the name proteoglycan. Various
proteoglycans are distributed in different tissues as under:

i. Chondroitin sulphate—abundant in cartilage, dermis

ii. Heparan sulphate—in basement membranes

iii. Dermatan sulphate—in dermis

iv. Keratan sulphate—in cartilage

v. Hyaluronic acid—in cartilage, dermis.

In wound healing, the deposition of proteoglycans precedes
collagen laying.

The strength of wound also depends upon factors like the site
of injury, depth of incision and area of wound. After removal of
stitches on around 7th day, the wound strength is approximately
10 percent which reaches 80 percent in about 3 months.
Degradation of Extracellular Matrix
Extracellular matrix is not a static structure but the matrix
proteins comprising it undergo marked remodeling. Localized
degradation of the ECM occurs so that cells can migrate across
the basal lamina to reach the site of injury. Locally secreted
family of metalloproteinases degrade the ECM components.
Proteolysis is tightly regulated. Many proteases are secreted as
inactive precursors that are activated when required. Protease
inhibitors such as tissue inhibitors of metalloproteinase
(TIMP) can bind these enzymes and block their activity.
Maturation Phase
It includes period of scar contraction with collagen cross-
linking and shrinking.
Contraction of Wounds
The wound starts contracting after 2 to 3 days and the process
is completed by the 14th day. During this period, the wound
is reduced by approximately 80 percent of its origi­nal size.
Contracted wound results in rapid healing since lesser surface
area of the injured tissue has to be replaced.

In order to explain the mechanism of wound contrac­tion, a
number of factors have been proposed. These are as under:
1. Dehydration as a result of removal of fluid by drying of
wound was first suggested but without being substantiated.
2. Contraction of collagen was thought to be responsible for
contraction but wound contraction proceeds at a stage when
the collagen content of granulation tissue is very small.
3. Discovery of myofibroblasts appearing in active granula­
tion tissue has resolved the controversy surrounding
the mechanism of wound contraction. These cells have
features intermediate between those of fibroblasts and
smooth muscle cells. Their migration into the wound
area and their active contraction decrea­ses the size of the
defect. The evidences in support of this concept are both
morphological as well as functional characteristics of
modified fibroblasts or myofibro­blasts as under:

i. Fibrils present in the cytoplasm of these cells
resemble those seen in smooth muscle cells.

History and Healing
Section 1
16

ii. These cells contain actin-myosin similar to that
found in non-striated muscle cells.

iii. Cytoplasm of these modified cells demonstrates
immunofluorescent
labelling
with
anti-smooth
muscle antibodies.

iv. Nuclei of these cells have infoldings of nuclear
membrane like in smooth muscle cells.

v. These cells have basement membrane and desmo­
somes which are not seen in ordinary fibroblasts.

vi. Drug response of granulation tissue is similar to that
of smooth muscle.
Suture Tracks
Each suture track is a separate wound and incites the same
phenomena as in healing of the primary wound, i.e. filling
the space with hemorrhage, some inflammatory cell reaction,
epithelial cell prolife­ration along the suture track from both
margins, fibroblastic proliferation and formation of young
collagen. When sutures are removed around 7th day, much
of epithelialized suture track is avulsed and the remaining
epithelial tissue in the track is absorbed. However, some­times
the suture track gets infected (stitch abscess), or the epithelial
cells may persist in the track (implantation or epidermal
cysts).

Thus, the scar formed in a sutured wound is neat due to
close apposition of the margins of wound; the use of adhesive
tapes avoids removal of stitches and its complications.
TYPES OF WOUND HEALING
Wound healing can be accomplished in one of the following
two ways:
• Healing by first intention (primary union)
• Healing by second intention (secondary union).
Healing by First Intention (Primary Union)
This is defined as healing of a wound which has the following
characteristics:

i. Clean and uninfected
ii. Surgically incised
iii. Without much loss of cells and tissue
iv. Edges of wound are approximated by surgical sutures.
Healing by Second Intention
(Secondary Union)
This is defined as healing of a wound having the follow­ing
characteristics:

i. Open with a large tissue defect, at times infected
ii. Having extensive loss of cells and tissues
iii. The wound is not approximated by surgical sutures but
is left open.

The basic events in both primary union and secondary
union are similar as have been described. However secondary
union differs in having a larger tissue defect which has to be
bridged. Hence healing takes place from the base upwards as
well as from the margins inwards. Also, the healing by second
intention is slow and results in a large, at times ugly, scar as
compared to rapid healing and neat scar of primary union.

Some basic differences in healing by secondary intention
are described below:
• Epithelial changes: As in primary healing, the epidermal
cells from both the margins of wound proliferate and
migrate into the wound in the form of epithelial spurs
till they meet in the middle and re-epithelialize the gap
completely. However, the proli­ferating epithelial cells do
not cover the surface fully until granulation tissue from
base has started filling the wound space. In this way, pre-
existing viable connective tissue is separated from necrotic
material and clot on the surface, forming scab which is cast
off. In time, the regenerated epidermis becomes stratified
and keratinized.
• Granulation tissue: Main bulk of secondary healing is by
granulations. Granulation tissue is formed by proliferation
of fibroblasts and neovascularisation from the adjoining
viable elements. The newly-formed granulation tissue is
deep red, granular and very fragile. With time, the scar on
maturation becomes pale and white due to increase in col­
lagen and decrease in vascularity. Specialized structures of
the skin like hair follicles and sweat glands are not replaced
unless their viable residues remain which may regenerate.
• Wound contraction: Contraction of wound is an important
feature of secondary healing, not seen in primary healing.
Due to the action of myofibroblasts present in granulation
tissue, the wound contracts to one-third to one-fourth of
its original size. Wound contraction occurs at a time when
active granulation tissue is being formed.
• Presence of infection: Bacterial contamination of an open
wound delays the process of healing due to release of
bacterial toxins that provoke necrosis, suppu­ration and
thrombosis. Surgical removal of dead and necrosed tissue,
debridement, helps in preventing the bacterial infection of
open wounds.

Differences between primary and secondary union of
wounds are given in Table 1.
FACTORS INFLUENCING HEALING
Wound failure may occur when the healing process is disrupted
prolonging the inflammatory phase and delaying subsequent
phases of wound healing.

Pathology of Wound Healing 
Chapter 2
17

Two types of factors influence the wound healing: those
acting locally, and those acting in general.
A. Local factors: These include the following factors:

1. Infection is the most important factor acting locally
which delays the process of healing.

2. Poor blood supply to wound slows healing, e.g. injuries
to face heal quickly due to rich blood supply while
injury to leg with varicose ulcers having poor blood
supply heals slowly.

3. Foreign bodies including sutures interfere with healing
and cause intense inflammatory reaction and infection.

4. Movement delays wound healing.

5. Exposure to ionising radiation delays granulation tissue
formation.

6. Exposure to ultraviolet light facilitates healing.

7. Type, size and location of injury determines whether
healing takes place by resolution or organization.
B. Systemic factors: These are as under:

1. Age: Wound healing is rapid in young and somewhat
slow in aged and debilitated people due to poor blood
supply to the injured area in the latter.

2. Nutrition: Deficiency of constituents like protein,
vitamin C (scurvy) and zinc delays the wound healing.

3. Systemic infection delays wound healing.

4. Administration of glucocorticoids has anti-inflam­
matory effect.

5. Uncontrolled diabetics are more prone to develop
infections and hence delay in healing.

6. Hematologic abnormalities like defect of neutrophil
func­tions (chemotaxis and phagocytosis), and neutro­
penia and bleeding disorders slow the process of wound
healing.
COMPLICATIONS OF WOUND HEALING
During the course of healing, following complications may
occur:
1. Infection of wound due to entry of bacteria delays the
healing.
2. Implantation (epidermal) cyst formation may occur due to
persistence of epithelial cells in the wound after healing.
3. Pigmentation: Healed wounds may at times have rust-
like color due to staining with hemosiderin. Some colored
particulate material left in the wound may persist and
impart color to the healed wound.
4. Deficient scar formation: This may occur due to inadequate
formation of granulation tissue.
5. Incisional hernia: A weak scar, especially after a
laparotomy, may be the site of bursting open of a wound
(wound dehiscence) or an incisional hernia.
6. Hypertrophied scars: At times the scar remains in the
remodeling phase for longer than usual and excess collagen
is produced. The hypertrophic scars are more cellular and
more vascular than mature scars. Clinically they are red,
raised, itchy and tender. These will eventually mature to
become pale and flat. The risk of developing a hypertrophic
scar can be minimized by ensuring quiet primary healing.
7. Keloid formation: Excessive formation of collagen in
healing may result in keloid (claw-like) formation, seen more
commonly in blacks. Keloids differ from hypertrophied scars
in that they have tumor-like projection of connective tissue
while hypertrophied scars are confined to the borders of the
initial wound. Keloids rarely regress with time.
8. Excessive contraction: An exaggeration of wound
contraction may result in formation of contractures or
cicatrisation, e.g. Dupuytren’s (palmar) contracture,
plantar contracture and peyronie’s disease (contraction of
the cavernous tissues of penis).
9. Neoplasia: Rarely, scar may be the site for develop­ment of
carcinoma later, e.g. squamous cell carcinoma in Marjolin’s
ulcer, i.e. a scar following burns on the skin.
NEW HORIZONS
In the past few years, our understanding of the mechanism
of wound healing has increased dramatically. This has led
to significant advances in complex acute and chronic wound
management. When dressings alone fail to achieve healing,
Table 1: Differences between primary and secondary union of wounds
Feature
Primary union
Secondary union
1.
Cleanliness of wound
Clean
Unclean
2.
Infection
Generally uninfected
May be infected
3.
Margins
Surgical clean
Irregular
4.
Sutures
Used
Not used
5.
Healing
Scanty granulation tissue at the incised
gap and along suture tracks
Exuberant granulation tissue
to fill the gap
6.
Outcome
Neat linear scar
Contracted irregular wound
7.
Complications
Infrequent, epidermal inclusion cyst formation
Suppuration, may require debridement

History and Healing
Section 1
18
the clinician turns to a variety of advanced therapeutics
modalities as under which are given in detail in subsequent
chapters.
• Negative pressure-assisted wound closure: It has been
demonstrated that application of sub-atmospheric pressure
helps in removal of edema, causes increase in local blood
flow and stimulates granulation tissue formation resulting
in faster healing.
• Topical application of growth factors to chronic wounds
has not been as beneficial as anticipated, presumably
because they are degraded by proteases in the wound fluid
• Researchers are now investigating whether localized gene
therapy may be a better delivery system for providing
growth factors.
• Dressings that actively alter the wound matrix are
currently being developed. One such device, oxidized
regenerated cellulose/collagen has been found to promote
human dermal fibroblast proliferation and cell migration.
• Biodegradable scaffolds may also alter wound milieu to be
more favorable.
SUMMARY
For all organisms healing of any wound is a biological
necessity and in the normal circumstances it takes place in
a phased manner and follows a predictable chain of events.
Although the process might vary in different types of tissues,
there are many similarities in all of them. Skin is considered
to be the representative tissue type where all the phases can be
explained easily. The end process of any wound healing is the
formation of a scar. The various advancements in technology
have expanded our knowledge of the healing process at
the molecular level, improved our ability to accelerate the
healing process and manage wounds in a logical manner thus
producing acceptable scars.
Bibliography
1. Danning CL. Alterations in musculoskeletal function: trauma,
infection and disease. In: Copstead LEC, Banasik JL (Eds).
Pathophysiology. 3rd edn. St Louis: Saunders. 2005. pp. 1252-
74.
2. Deodhar AK, Rana RE. Surgical physiology of wound healing:
a review. J Postgrad Med. 1997;43:52.
3. Ethridge RT, Leong M, Phillips L. Wound healing. In: Touen-
send CM, Beauchamp RD, Evers BM, Mattox KL (Eds).
Sabiston Textbook of Surgery The Biological Basis of Modern
Surgical Practice. 18th edn. Philadelphia: Saunders. 2009. pp.
191-216.
4. Kumar V, Abbas AK, Fausto N, Aster JC. Tissue renewal,
repair, and regeneration. In: Kumar V, Abbas AK, Fausto
N, Aster JC (Eds). Robbins and Cotran Pathologic Basis of
Disease. 8th edn. Pennsylvania: Saunders. 2010. pp. 79-110.
5. Sephel GC, Woodward SC. Repair, regeneration and fibrosis.
In: Rubin E, Gorstein F, Rubin R, Schwarting R, Strayer D
(Eds). Rubin’s Pathology Clinicopathologic Foundations of
Medicine. 4th edn. Philadelphia: Lippincott Williams and
Wilkins. 2001. pp. 85-116.
6. Werner S, Grose R. Regulation of wound healing by growth
factors and cytokines. Physiol Rev. 2003;83:835-70.
7. Williams NS, Bulstrode CJK, O’connell PR. Wounds, tissue
repair and scar. In: Williams NS, Bulstrode CJK, O’connell PR
(Eds). Bailey and Love’s Short Practice of Surgery. 25th edn.
London: Edward Arnold Publishers. 2008. pp. 24-31.

• Hemostatic Phase
• Inflammatory Phase
• Proliferative Phase
• Remodeling Phase
• Fibrotic/Chronic Wounds
• Management of Fibrotic Wounds

– Anti-inflammatory Agents

– Growth Factor Inhibition

– Proapoptotic Agents
• Chronic Ulcers and its Implications
• Wound Dressing and its Characteristics
• Skin Substitutes
• Tissue Engineering
• Stem Cells
Introduction
A wound is a break in the integrity of the skin or tissues often,
which may be associated with disruption of the structure and
function.1 Wounds can be classified as simple wounds and
complex wounds; closed wounds and open wounds; tidy and
untidy wounds; clean wound, clean contaminated wound,
contaminated wound and dirty wound; acute wounds and
chronic wounds.

Over the past two decades, extraordinary advances in
cellular and molecular biology have greatly expanded our
comprehension of the basic biological process involved in
acute wound healing and the patho biology of the chronic
wounds. Wound healing is a complex, dynamic and a well
orchestrated process which has overlapping but distinct
phases to promote tissue repair. The phases of wound healing
entails hemostasis, inflammation, migration, proliferation
and remodeling.2,3 There are various cell to cell and cell to
matrix interactions which influence the various phases in
bringing restorative repair.4,5 The exact pathology of wound
healing has been already been discussed in the previous
chapter.

Signaling cascades and fruitful crosstalks within the
various molecules involved in wound repair are critical for the
healing mechanism to move apace without being stymied.6
The complexity derived from cellular migration, proliferation,
differentiation and tissue remodeling has to be properly
coordinated with the requisite elements at the requisite time
and disappearance of these after the task is over.7 This is of
primary interest as the redundance of elements after the job is
a burden to the healing milieu even to the extent of disrupting
wound repair. This chapter enumeratis the advances that have
been made in bringing out never would care products which
enhance different phases of wound healing.
Hemostatic phase
When a tissue gets injured the subendothelial collagen gets
exposed. Platelets bind to the exposed collagen and become
activated. Platelet adhesion and aggregation are primed by
the release of thrombospondin, fibronectin, von Willebrand
factor, etc.8 A provisional matrix namely fibrin matrix is being
laid down. Hence, a stable clot is formed.9

Platelets release some mediators namely platelet derived
growth factor (PDGF), transforming growth factor beta, trans-
forming growth factor alpha. PDGF recruits fibroblasts and aug-
ments laying down of collagen and glycosaminoglycans.10-12
Mary Babu, Ranjith James Babu, S Shanmuganathan
Recent Advances in Wound
Healing
3
Chapter

History and Healing
Section 1
20
There is a significant role of apoptosis whereby these media-
tors are eliminated from the wounded milieu once the requi-
site job is over.13 These mediators invite inflammatory cells
to the wounded loci which forms the basis to the next phase.
Moreover, the hemostatic plug seals the wound site and pro-
vides a platform for migration of cells and growth factors to
aid in the subsequent phases of wound repair.14,15
Inflammatory Phase
Subsequent to injury, inflammatory cells invade the wounded
site by cross talks with the released chemokines. It begins
within the first 24 hours post injury. Neutrophils form the
predominant inflammatory cells in the acute phase. Myriad
signaling pathways are activated and in particular endothelial
cells which are activated begin to express selections which
are cell adhesion molecules (CAM). These CAMs latch on
to the neutrophils to bind them to the endothelial cells. By
diapedesis, the neutrophils reach the inflammatory site by
squeezing through the cell junctions.16,17 To travel in the
extracellular matrix, neutrophils release enzymes that degrade
the matrix namely elastase and matrix metalloproteinase.18
Neutrophils get rid of the foreign particles, debris, bacteria
and damaged extracellular components in the wounded milieu.
They activate fibroblasts and epithelial cells by releasing IL-1
and tumor necrosis factor-a. Then the chronic phase ensues
spearheaded by macrophages and monocytes which are
activated by various growth factors, cytokines, chemokines
and soluble fragments of extracellular matrix components.19
They phagocytose these elements and further progress healing
by secretion of growth factors and cytokines thereby inviting
endothelial cells and fibroblasts for deposition of matrix and
neovascularization.

Studies show the role of chemokines in recruiting
inflammatory cells onto the wound site suggesting its role for
angiogenesis and tissue remodeling. The important receptor
is CXC receptor which binds three multiple ligands such as
interferon gamma inducible protein-10 (IP10), Interferon
gamma inducible protein-9 (IP9) and platelet factor IV.20-22
During wound healing, IP10 is shown to be expressed in deep
dermal layer of vascular endothelial cells which inhibits
endothelial cell proliferation, migration and angiogenesis.23
Overexpressing this chemokine in vivo resulted in intense
inflammatory phase, disorganized granulation tissue formation
and impaired angiogenesis resulting in the inhibition of
re-epithelialization.24,25 IP9 is expressed by basal cells of
keratinocytes and it stimulates keratinocyte migration.

This inflammatory phase is also called as lag phase since
the tensile strength is very minimal derived from fibrin and
fibronectin. Clinically features of inflammation are calor,
dolor, rubor, tumor and loss of function.
Proliferative Phase
The proliferative phase is also called as the collagen phase.
The phase commences with the migration and proliferation of
keratinocytes. Re-epithelialization phase starts immediately
within hours after injury. Keratinocytes participating in
re-epithelialization originate from the epidermis near the
cut edge of the wound.26,27 Stimuli for the migration and
proliferation of epidermal cells is due to the expression of
growth factors and certain chemokines.28,29 Over the past
decade, several chemokines had been identified as well as
their receptors in wound healing. Various cytokines and
growth factors which are released by the inflammatory cells
attracts the myofibroblasts and fibroblasts into the wounded
site. Fibroblast activity is regulated predominantly by PDGF
and TGF-b. Hence, a stable extracellular matrix is created
by replacing the provisional fibrin matrix. The extracellular
matrix thereby formed consists of collagen, fibronectins and
proteoglycans. TNF-a and basic FGF activates endothelial
cells. The process of angiogenesis occurs whereby damaged
capillaries are replaced. Moreover, fibroblasts require oxygen
and nutrients to create the extracellular matrix and hence
angiogenesis is of primary interest.

Angiogenesis occurs by a balance between proangiogenic
and antiangiogenic factors. Proangiogenic factor comprises of
vascular endothelial growth factor and antiangiogenic factor
comprises of endostatin, angiostatin, thrombospondin and
pigment epithelium derived growth factor. There are local
factors as well which dictate the process of angiogenesis.
These include low pH, low oxygen tension and elevated lactate
levels. Tissue oxygen level directly influences antiangiogenic
stimulus. It does so in low oxygen tension wherein hypoxic
inducible factor-1 present inside the endothelial cells binds to
specific DNA sequences to stimulate transcription of VEGF,
thereby promoting angiogenesis.30

Although angiogenesis is extremely important in initial
stages of wound healing extensive vascularization causes
pathological condition such as fibrosis.31 The optimum level
of blood vessels depends on timely expression of angiogenic
and angiostatic factors during vascularization.

As the reparative process continues granulation tissue is
being formed by the deposition of extra cellular matrix proteins
by the fibroblasts and keratinocytes. Granulation tissue consists
of capillary loops supported in the developing collagen matrix.
When an abundance of collagen matrix is formed, the collagen
production is switched off by the fibroblasts. The inflammatory
cells become negligible during this phase due to apoptosis.

Regulative cell motility is critical to wound healing.
Active cell locomotion requires coordination of the number
of cellular process and signaling pathways. Cell migration is
dysregulated in chronic nonhealing wounds. Identification of

Recent Advances in Wound Healing 
Chapter 3
21
factors that control cell migration serves a promising approach
to modulate cell behavior.

Apoptosis or programmed cell death provides channels for
elimination of unneeded cells and tissues. As there is transition
from inflammatory to proliferative phase, inflammatory cells
in the wounded milieu become less and less due to apoptosis.32
Remodeling Phase
During the maturation or the remodeling phase, granulation
tissue matures into a scar. Fibroblasts slowly disappear
from the wound bed by apoptosis. There has to be a balance
between collagen synthesis and degradation. Collagen is
remodeled into a more organized matrix.32,33 The organization
of collagen fibers amounts to the tensile strength of the wound.
Initially type III collagen (reticular collagen) is replaced by
type I collagen (fibrillar collagen).34 The remodeling of the
scar tissue happens to take place over weeks to months. The
point to note is that the scar tissue never attains the tensile
strength of the uninjured skin. A maximum of 80 percent
tensile strength of normal tissue is obtained.35

During the remodeling phase, the wound hypervascularity
should decrease. Macrophages help in this process by lessening
the antiangiogenic stimuli. This prevents the formation of new
blood vessels but does not disrupt the vessels already existing
in the wound bed.

Extracellular zinc dependant endopeptidases called
matrix metalloproteinases (MMPs) control degradation of
extra-cellular matrix components. MMPs are secreted by
epidermal cells and are regulated by TGF-b. Net effect on
tissue remodeling is cemented by fruitful interactions between
MMPs and tissue inhibitors of matrix metalloproteinases
(TIMPS).36
Fibrotic/Chronic Wounds
In an optimal wound healing, there is a striking balance
between connective tissue formation and destruction. When
this mechanism is dysregulated due to various causes in
a prone individual there can be dichotomous effect. One
in which there is fibrosis leading to hypertrophic scars and
keloids. Another in which the continous destruction of newly
formed connective tissue leading to chronicity of the wound.
Management of Fibrotic wounds
Anti-inflammatory Agents
Corticosteroids has been the drug of choice as it downplays
extracellular matrix protein synthesis, decreases inflammatory
protein production, inhibits collagen and neovascularization
and decreases cytokine production to aid in scar management.37
Triamcinolone, a long acting synthetic glucocorticoid is
commonly used for treatment of hypertrophic and keloid
scars. Concentrations of 10 to 40 ng/ml injected Intrakeloidal
or into the hypertrophic scar helps with the scar reduction.38
This is a therapeutic intervention and steroids are not aimed at
prophylactic measures.

Methods to control inflammation can be aimed at any of
the three measures which include: (a) Inhibition of NF-KB
pathways, (b) Inhibition of prostaglandin production via
cyclooxygenase (COX) regulation, (c) Inhibition of histamine
synthesis. Nonsteroidal anti-inflammatory drugs that has
found a formidable position in the management of analgesia
nowadays act through the NF-KB pathway or Cox pathway or
in both of them. Aspirin is found to inhibit NF-KB pathway
and also irreversibly inactivates both COX isoforms.39

Antihistamines display antifibrotic effects. They seem to
downplay the inflammatory sequence offering a decrease
in the scar formation.40 Pheniramine maleate which comes
under the antihistamine group decreases the rate of collagen
synthesis in scar environment.41 Hence, this might give a new
dimension in treating keloids and hypertrophic scars.

Vitamin D3 acts by inhibiting NF-KB. It can be aimed at
controlling scar growth.
Growth Factor Inhibition
The transforming growth factor b (TGF-b) family of proteins,
when bound to its receptor causes fibroblast proliferation and
extracellular matrix synthesis. Hence, TGF-b binding to its
receptor limited by Mannose-6-phosphates and several other
disaccharides helps to limit scar formation in experimental
wound healing models.42 This needs to be translated to the
patient care setting.
Proapoptotic Agents
Apoptosis or programmed cell death is considered as cardinal
feature in wound repair and its regulation. It has been shown
in the literature that keloid fibroblasts have a lower apoptotic
rate than normal fibroblasts.43,44 Keloids fibroblast display
enhanced apoptosis rates in response to hydrocortisone, gama
interferon and hypoxia treatment.

As keloids possess thick and dense collagen, proapoptotic
agents will minimize scar area, thereby regulating its effects.
Chronic ulcers and its
implications
Numerous molecular changes have been associated with
diabetic complications.

History and Healing
Section 1
22

Chronic ulcers are driven by increased inflammation,
overexpression of oxygen driven free radicals, oxidative stress,
neuropathy, angiopathy, immunopathy and overexpression
of matrix metalloproteinases. It is usually a permanent in­
flammatory response with high proteolytic activity and
degradation. It is treated primarily by addressing the etiology
behind the chronicity (arterial, venous, neuropathic, dia­betic,
leprotic, tuberculous, decubitus ulcers, etc.). Then antioxidants,
vitamins are given along with local care of the wound area
by debriding agents, antibiotics, growth factors and wound
dressings to bring salubrious effects.45 Recombinant platelet
derived growth factor-BB is the only growth factor approved
for use in chronic wounds.46,47

Recently, epigenetic events which are changes in gene
transcription or phenotype that are not result of changes in
DNA sequence have been identified in diabetic. Dysregulation
of cytokines and growth factor levels may prolong the in­
flammatory phase which hinders the progression of subsequent
phases. Keratinocytes at wound site present impaired abilities
to migrate, proliferate and differentiate.

Endothelial progenitor cells (EPCs) are requited from the
basement membrane as a response to injury and are homed
to the site of injury to mediate neovasculogenesis.50 This
is initiated by VEGF, which is released by cells such as
fibroblasts, macrophages and epithelial cells at the site of
injury. This triggers the activation of the eNOS in the bone
marrow, to produce nitric oxide which is required to trigger the
migration of EPCs into the blood-stream.51 The EPCs are then
homed to the site of injury by the cytokine SDF-1α. People
with type 1 and type 2 diabetes can have decreased levels of
EPCs, and the existing cells may have impaired function and
diminished ability to migrate to the site of injury.52-56 Using a
mouse model, it has been shown that this process is impaired
in diabetes because of impairment in the phosphorylation of
eNOS, and therefore, the migration of the EPC into the blood-
stream.57 The study also showed that decreased production
of SDF-1α from myofibro blasts and epithelial cells impaired
recruitment of the EPCs to the site of injury.
Wound dressing and its
characteristics48
Wound dressings protect the wound from contaminating
bacteria by providing surface coverage. There are a number
of wound dressings in the market which have to be used
according to the condition of the wound and the phases of the
wound healing. The general functions of an ideal dressing are
as follows:
1. Wound cleansing
2. Removal of excess exudate
3. Provide a moist wound environment
4. Promotes gaseous exchange
5. Prevents invasion of microbes
6. Promotes normal tissue temperature
7. Prevents trauma
8. Easily available
9. Cost effective.

Topical formulations are prepared in the form of semisolid
and liquids. Physiological saline is used to clean wounds and
to remove unviable tissues. It also helps to remove dressings
(gauze pads) with minimal pain. Antibacterial preparations
help to control or prevent infection. Traditional wound
dressings such as gauze, tulle dressings protect the surface of
the wound from further injurious elements. Gauze pads used
for packing the wounded area help in absorbing fluid and
exudate from the environment.

Modern wound dressings present a moist environment
to facilitate healing. Hydrocolloids, alginates and hydro-
gels are used in various forms as gels, thin films and foam
sheets to perform this role.48-50 Biological dressings make
use of tissue engineered products which are derived from
natural tissues. Collagen,51-53 cellulose, hyaluronic acid,
elastin, chitosan and alginates make up this group. Also,
gelatin which is a natural polymer that is derived from col-
lagen which is biocompatible and biodegradable is incor-
porated with growth factors to promote accelerated wound
healing.54,55 Notably, fibrin a protein matrix produced from
fibrinogen acts as a scaffold promoting cell adhesion, migra-
tion and proliferation.56,57 Here, the biocompatible and non-
toxic nature of these wound dressings to the resident cells
play a constructive role in designing these as polymers for
delivering optimal cure.

Silver has been used in wound dressings of some topical
formulations to manage infected wounds. Controlled deliv-
ery of SSD through alginate microspheres embedded in col-
lagen dressings is a novel delivery system to control wound
infections. Chen et al. (2008) have successfully produced a
composite nano fiber membering composed of collagen and
chitosan to promote quick and scar less wound healing.

Growth factors such as transforming growth factor b 1,
platelet derived growth factor, basic fibroblast growth factor,
epidermal growth factor have been incorporated in the bio-
compatible scaffolds to speed the repair process targetting cell
signaling, dermal maturation and re-epithelialization.

Bilayered membranes have been designed which incorpo­
rate antibiotics into the structural matrix to ward off infections.
The top layer is made of dense material to prevent mechanical
disruption and the bottom layer is a sponge like layer to drain
the wound exudates and to get attached to the wound surface
to promote the requisite tissue healing.

Recent Advances in Wound Healing 
Chapter 3
23
Skin Substitutes
This type of wound dressing helps with structural support
and scaffolding for regeneration. Integra, alloderm and
apligraf come under this category. Intergra consists of two
layers. The first layer is made of cross linked bovine collagen
and chondroitin 6 sulphate which is a glycosaminoglycan.
This layer serves as a template for infiltration of various
cellular elements comprising of fibroblasts, macrophages,
lymphocytes and capillaries from the wound bed. The second
layer comprises of silicone which regulates the moisture in the
wound bed. The physiological effects of post burn hands treated
with Integra appears promising.58 Alloderm is designed from
the human skin tissue. It comprises of acellular dermal matrix
which aids in revascularization and gets incorporated into the
host tissue. Its fabrication and application has been studied in
an in vivo acute wound model.59 Apligraf is a living bilayered
dressing where the bottom layer has dermal fibroblasts derived
from neonate, cultured in a collagen matrix for a period of 6
days. Then human keratinocytes are cultured on top of this.
Although it contains matrix proteins and expresses cytokines,
it is devoid of melanocytes, macrophages, lymphocytes,
Langerhans cells. Of late, extensive research has been
focussed on building skin substitutes containing melanocytes
and sweat glands.
Tissue Engineering
Tissue engineering and regenerative medicine are expected
to be powerful tools for wound healing applications in the
21st century. It has emerged as a constructive and critical
discipline in the armamentarium of wound repair. It is an
interdisciplinary approach wherein many departments of
the medical community get involved. The basic concept is a
combination which involves cells, a mechanical biomaterial
framework which is biocompatible and the local milieu which
is critical for cross talks and cell signaling to promote cell
proliferation, migration and in organizing a provisional matrix.

In this regard, the development of implantable matrices
is of importance. These simulate the natural tissues since
collagen, gelatin are in the native milieu. Considerable
research has been undertaken to design tissue engineering
scaffolds with defined structures using extracellular matrix in
3 dimensions (3D). They come in two forms (acellular and
cellular containing matrices). Acellular matrices are made
from synthetic collagen with extracellular matrix or from a
native dermal layer with deficit of cellular components.60-62
The cell containing matrices are biodegradable films which act
as scaffold facilitating ingrowth of resident skin cells. These
scaffold bear the anatomic and mechanical characteristics
closer to the native tissues.63-66 These scaffolds can also be
primed with bioactive materials in the form of growth factors,
antimicrobials and genetic materials to speed up the healing
process.

Fibrous scaffolds composed of polycaprolactone, poly­
hydroxybutyrate and polyethylene terephthalate with the
technology of interfacial polyelectrolyte complexation have
considerable infrastructure encouraging cell migration, cell
signaling and controlled release of growth factors. It provides
an ideal environment where cell anchorage, signal transduction
are primed to offer the smooth functioning of intracelluar and
extracellular events in regulating tissue repair.67 A number
of synthetic and natural materials and different process have
been used to fabricate scaffolds with different fiber diameters.
Electrospun scaffolds using collagen and chitosan as natural
materials and poly lactic acid, poly caprolactone and poly
glycolic acid as synthetic material have been developed as
scaffolds for tissue engineering.

For effective wound therapy, the active substances required
have to be delivered at the site and scientists are forced to
develop multi functional and complex delivery systems.
The sustained release of a desired drug can be formulated as
liposomes, microparticles or nanoparticles. Drug encapsulated
within microparticles (1–1000 µm) and nanoparticles
(1–1000 nm) is achieved with polymers both synthetic,
natural and modified natural polymers. The most commonly
preferred polymers in wound healing are biodegradable and
biocompatible polymers which include collagen, gelatin,
hyaluronic acid, chitosan, polylactic acid and poly glycolic
acid. A new technology using three dimensional construct is
the bioprinted nanoparticle application where manipulation
of cells along with tracking of cells and bioactive factors to
achieve desired tissue repair.68
Stem Cells
Stem cells give a new dimension to the wound healing
trajectory. They are cells capable of differentiating into
variegated cells. They also has the capacity of renewing
themselves. They are controlled by intricate signals dictated
by the cellular microenvironment. Some of the intricacies
relate to the soluble factors in the tissue, local environment
and indispensible cell signaling pathways. Significant efforts
were made by Till and McCulloch in 1961 in coining the term
stem cells. They are present in almost all cells in the body.

Bone marrow mesenchymal stem cells (BMSCs) which
are progenitors of the keratinocytes, fibroblasts and fibrocytes
play a role in wound healing.69-72 Adipose derived stem cells
(ASCs) which are obtained from fat or lipoaspirated fat have
been found to differentiate into cells of the mesenchyme.73,74
Moreover, ASCs promote angiogenesis, vasculogenesis and
secrete growth factors.75,76

History and Healing
Section 1
24

A novel chitosan microsphere (CSN) loaded with SSD
impregnated into a pegylated fibrin gel was developed to
be used as an antibacterial in wound healing. Evidence is
provided that this composite fibrin gel supports vessel like
tube formation by adipose derived stem cells (ASCs) in vitro.
In another study chitosan fibrous scaffolds were coated with
collagen type II and mesenchymal stem cells. This resulted
in formation of cell clusters and promoted cadherin mediated
cell to cell interaction in vitro.

Works revealing the capability of ASCs to differentiate into
keratinocytes and to produce keratinocyte growth factor and
vascular endothelial growth factor are encouraging. Another
study which was quite convincing revealed ASCs promoting
epidermal regeneration and epithelial integrity.77
Summary
A lot of work has gone through decades in designing and
dressings for wounds. Over the period, a lot of understanding
into wound healing has paved way to aptly apply dressings
suitable to the healing phase. From packing wounds with gauze,
tulle to setting up a system with stem cells speaks volumes
of research and innovation in this field. Even now at present,
work is in progress in this multidisciplinary field in building
wound healing systems and stem cell incorporated scaffolds
which are milestones in wound healing technology. Quite
hopefully, these are expected to translate into meaningful and
beneficial interventions for human race in the years to come.
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• Classifi cation
• Hypertrophic Scars Versus Keloids
• Scar Assessment
• Management

– Nonsurgical

– Surgical Modalities
INTRODUCTION
The word scar is derived from Old French word escharre,
from old Latin word eschara, which is the latinization of the
Greek word (eskhara), meaning “hearth, fi re-place”.

Excessive scarring was fi rst described in the Smith
papyrus about 1700 BC.1 Many years later Mancini (in 1962)
and Peacock (in 1970) differentiated excessive scarring into
hypertrophic and keloid scar formation. As per their defi nition,
both scar types rise above skin level, but while hypertrophic
scars do not extend beyond the initial site of injury, keloids
typically project beyond the original wound margins.2,3

In medical terminology (etiopathologically), scar is non-
regenerative wound healing. But for a patient it is a visible
continual reminder of its cause, attracting attention and generating
self-consciousness. Wound healing process and scar formation
have already been covered in previous chapters in detail.

A well healed invisible scar is not only of great satisfaction
to the patient and doctor but is also the visiting card of the
plastic surgeon.
CLASSIFICATION
Scars can be classifi ed in different ways:
1. According to Type of Trauma Infl icted

a. Surgical scars produced after any surgery. These are
usually not contaminated and so heal by primary intention.

b. Non-surgical scars due to different types of trauma
like lacerated wound, abrasion/friction wounds, burn
wounds, gunshot wounds, bite wounds, crush wounds,
scars due to infection.
2. According to Appearance of Scar

a. Mature scar is fl at, soft and supple scar with color
matching that of surrounding skin (Figures 1A and B).

b. Immature scar is a red, sometimes itchy or painful and
slightly elevated scar in the process of remodeling.
Many of these will mature normally over time and
become fl at, and assume a pigmentation that is similar
to the surrounding skin, although they can be paler or
slightly darker (Figure 2).

c. Unstable scar is usually a scar over an area of stress
which breaks down repeatedly as over a joint or
subcutaneous bone, etc. (Figure 3).

d. Pathological scar is an abnormal scar due to excess or
defi cient collagen synthesis. This is again sub-classifi ed
as:


• Atrophic scar are depressed below the skin surface
and are the result of decreased collagen synthesis or
increased collagen degradation (Figure 4). These are
seen more frequently in collagen disorders, leprosy
and patients taking steroids.
Atrophic scars are divided into four main types:
ice pick, boxcar, shallow/atrophic, and valley/rolling
scars.
Ice pick scars are typically small (1–2 mm) and
have a wide aperture with steep edges that taper to
a single point at the base, as if the skin has been
pierced by an ice pick. An epithelial tract forms
Sujata Sarabahi, Pratap Duggirala
Scars Following Wound Healing
4
Chapter

History and Healing
28
along the sides of the opening within the scar. These
scars may be shallow or deep, and may extend as far
as the dermal–subcutaneous junction.
Boxcar scars are round to oval in shape with
well-defi ned vertical edges and a fl at base, as if the
scar has been punched out of the skin. They typically
range from 0.1 to 0.5 mm in depth and are usually
widely spaced out on the skin surface, occurring as
solitary scars.




Unlike ice pick scars, this type of scar does not
converge to a single point.
Shallow/atrophic scars present as a cluster of
miniaturized boxcar scars. They usually emerge
in groups of four or more and occur mainly on the
cheeks.
Figures 1A and B: Mature scar
Figure 2: Immature scar
Figure 3: Unstable scar over shin of tibia
Valley scars (“rolling” scars) are deeper and have
an undulating appearance that is best appreciated in
indirect lighting. Valley-shaped scars arise from a
variable loss of dermis and/or subcutaneous tissue.
Because acne and varicella scars are dermal defects,
they require a treatment modality that reaches the
dermis in order to achieve clinical improvement.


• Hypertophic scars are classifi ed into two types:4
1. Linear hypertrophic (e.g. surgical/traumatic) scar
(Figure 5)—A red raised, sometimes itchy scar
confi ned to the border of the original surgical
incision. This usually occurs within weeks after
surgery. These scars may increase in size rapidly
for three to six months and then, after a static
phase, begin to regress. They generally mature to
A
B

Scars Following Wound Healing
29
Figure 4: Atrophic scar
have an elevated, slightly rope-like appearance
with increased width, which is variable. The full
maturation process may take up to two years.



2. Widespread hypertrophic (e.g. burn) scar (Figure
6)—A widespread red, raised, sometimes itchy
scar that remains within the borders of the burn
injury.


• Keloid are classifi ed into two types:4



1. Minor keloid—A focally raised, itchy scar exten-
ding over normal tissue. This may develop up to
one year after injury and does not regress on its
own. Simple surgical excision is often followed by
recurrence. There may be a genetic abnormality
involved in keloid scarring. Typical sites include
earlobes (Figures 7A and B).



2. Major keloid—A large, raised (0.5 cm) scar,
possibly painful or pruritic and extending over
normal tissue. This often results from minor
trauma and can continue to spread over years
(Figures 8A and B).
HYPERTROPHIC SCARS VERSUS
KELOIDS
Clinical Characteristics
Hypertrophic scarring usually occurs within four to eight weeks
following wound infection, wound closure with excess tension
or other traumatic skin injury, has a rapid growth phase for up to
six months, and then gradually regresses over a period of a few
years, eventually leading to fl at scars with no further symptoms.

Keloids, in contrast, may develop up to several years
after minor injuries and may even form spontaneously on the
Figure 5: Linear hypertrophic scar over sternal area
Figure 6: Widespread hypertrophic scar following burns
midchest in the absence of any signifi cant injury. Keloids also
persist, usually for long periods of time, and do not regress
spontaneously. They appear as fi rm, mildly tender, bosselated
tumors with a shiny surface and sometimes telangiectasia.
The epithelium is thinned and there may be focal areas of
ulceration. The color is pink to purple and may be accompanied
by hyperpigmentation. The borders of the tumor are well
demarcated but irregular in outline. A hypertrophic scar has
a similar appearance, but is usually linear, if following a
surgical scar, or papular or nodular, if following infl ammatory
and ulcerating lesions. Both lesions are commonly pruritic,
but keloids may even be the source of signifi cant pain and
hyperesthesia.

History and Healing
30
Figures 7A and B: (A) Minor keloids on earlobe following earpiercing and (B) Presternal region following surgical incision
Figures 8A and B: Major keloids (A) over shoulder and following injection (B) over abdomen following burns

In majority of the cases, hypertrophic scarring develops
in wounds at anatomic locations with high tension, such as
shoulders, neck, presternum, knees and ankles, whereas
anterior chest, shoulders, earlobes, upper arms and cheeks
have a higher predilection for keloid formation. Keloids tend
to recur following excision, whereas new hypertrophic scar
formation is rare after excision of the original hypertrophic
scar. The occurrence of keloids and hypertrophic scars has
equal sex distribution and the highest incidence in the second
to third decade. Incidence rates of hypertrophic scarring vary
from 40 to 70 percent following surgery to up to 91 percent
following burn injury, depending on the depth of the wound.
Keloid formation is seen in individuals of all races, except
albinos, but dark-skinned individuals have been found to be
more susceptible to keloid formation, with an incidence of
6 to 16 percent in African populations. The concept of a
genetic predisposition to keloids has long been suggested.5
Histology
Histologically, both hypertrophic scars and keloids contain
an overabundance of dermal collagen. Hypertrophic scars
contain primarily types III collagen oriented parallel to
the epidermal surface with abundant nodules containing
myofi broblasts, large extracellular collagen fi laments and
plentiful acidic mucopolysaccharides. Keloid tissue, in
contrast, is mostly composed of disorganized types I and
III collagen, containing pale-staining hypocellular collagen
B
A
B
A

Scars Following Wound Healing
31
bundles with no nodules or excess myofi broblasts. Both
scar types demonstrate overproduction of multiple fi broblast
proteins, including fi bronectin, suggesting either pathological
persistence of wound healing signals or a failure of the
appropriate downregulation of wound-healing cells.5
SCAR ASSESSMENT6
There are many different subjective and objective tools for
scar assessment, but there is currently no general agreement
on the most appropriate tool for scar evaluation. Scar scales
have been devised to quantify scar appearance in response
to treatment. There are currently at least fi ve scar scales that
were originally designed to assess subjective parameters in an
objective way: The vancouver scar scale (VSS), manchester
scar scale (MSS), patient and observer scar assessment scale
(POSAS), visual analog scale (VAS), and stony brook scar
evaluation scale (SBSES) (Table 1).
Vancouver Scar Scale
The vancouver scar scale (VSS), fi rst described by Sullivan
in 1990, is perhaps the most recognized burn scar assessment
method. It assesses four variables: vascularity, height/thickness,
pliability, and pigmentation. Patient perception of his or her
respective scars is not factored in to the overall score. Lye et al
compared the pliability score from the VSS to measurements
obtained through tonometry, noting moderate correlation in
scores. The VSS remains widely applicable to evaluate therapy
and as a measure of outcome in burn studies (Table 2).
Visual Analog Scale
The multidimensional visual analog scale (VAS) is a
photograph-based scale derived from evaluating standardized
digital photographs in four dimensions (pigmentation,
vascularity, acceptability, and observer comfort) plus contour.
Table 1: Comparison of scar assessment scales*,†
Scale
Scoring system
Attributes analyzed
Defi ciencies
Advantages
Vancouver
Scar Scale
0 to 13
Vascularity, height/
thickness, pliability,
and pigmentation
Lacks patient perception
Pigmentation subscale
less applicable to large,
heterogeneous scars.
Operator-dependent errors
Excludes pain and pruritis
Used widely in literature
for outcome measure in
burn studies
Visual Analog Scale
with Scar Ranking
0 to 100
“excellent”
to “poor”
Vascularity,
pigmentation, accept-
ability, observer comfort
plus contour and sum-
ming the individual scores
Photo-based scale does not
include patient assessment
Simpler than VSS
Assessments of intra- and
inter-rater reliability easier
to conduct
Patient and Observer
Scar Assessment
Scale
5 to 50
VSS plus surface area;
patient assessments
of pain, itching, color,
stiffness, thickness,
relief
Items represented may not
adequately express patient’s
perceptions and concerns
Focuses on scar severity
from clinician’s and
patient’s points of view
Manchester Scar
Scale
5 (best) to
18 (worse)
VAS plus scar color,
skin texture, relationship
to surrounding skin,
texture, margins, size,
multiplicity
Arbitrary assessment and
weighting of items
Applicable to a wider
range of scars. Uses
descriptors related to
clinical signifi cance
instead of physical
measurement alone
The Stony
Brook Scar
Evaluation Scale
0 (worst) to
5 (best)
VAS plus width, height,
color, presence of
suture/staple marks
Photo-based scale does not
include patient assessment.
Not designed for long-term
scar assessment
Specifi cally developed
to assess short-term
appearance of repaired
lacerations
*VAS indicates Visual Analog Scale; VSS indicates Vancouver Scar Scale.
†None of the scar scales measure the following:
1. The amount of total body surface area that is scarred.
2. The functional disability caused by scar.
3. The effects of pain and pruritus in terms of activities of daily living.

History and Healing
32
It sums the individual scores to get a single overall score
ranging from “excellent” to “poor.” It has demonstrated high
observer reliability and internal consistency when compared
to expert panel evaluation, but it has shown only moderate
reliability when used among lay panels.
Patient and Observer Scar Assessment
Scale
The patient and observer scar assessment scale (POSAS)
includes subjective symptoms of pain and pruritis and
expands on the objective data captured in the VSS. It consists
of two numerical numeric scales: The Patient Scar Assessment
Scale and the Observer Scar Assessment Scale. It assesses
vascularity, pigmentation, thickness, relief, pliability, and
surface area, and it incorporates patient assessments of pain,
itching, color, stiffness, thickness, and relief. The POSAS is
the only scale that considers subjective symptoms of pain
and pruritis, but like other scales it also lacks functional
measurements as to whether the pain or pruritis interferes with
quality of life. Linear regression analysis has demonstrated
T able 2: The Vancouver scar scale
Scar characteristic
Score
Vascularity
Normal
Pink
Red
Purple
0
1
2
3
Pigmentation
Normal
Hypopigmentation
Hyperpigmentation
0
1
2
Pliability
Normal
Supple
Yielding
Firm
Ropes
Contracture
0
1
2
3
4
5
Height
Flat
<2 mm
2–5 mm
>5 mm
0
1
2
3
Total score
13
Ta ble 3: Patient and observer scar assessment scale
Observer component
Normal skin
1
2
3
4
5
6
7
8
9
10
Worst scar imaginable
Vascularization
Pigmentation
_Hypo
_Mix
_Hyper
Thickness
Relief
Pliability
Patient component
No, no complaints
1
2
3
4
5
6
7
8
9
10
Yes, worst imaginable
Is the scar painful?
Is the scar itching?
No, as normal skin
1
2
3
4
5
6
7
8
9
10
Yes, very different
Is the color of the scar different?
Is the scar more stiff?
Is the thickness of the scar
different?
Is the scar irregular?
that the observer’s opinion is infl uenced by vascularization,
thickness, pigmentation, and relief, whereas the patient’s
opinion is primarily infl uenced by pruritis and scar thickness.
The POSAS has been applied to post surgical scars and used
in the evaluation of linear scars following breast cancer
surgery, demonstrating internal consistency and inter observer
reliability when compared to the VSS with the added benefi t
of capturing the patients’ ratings (Table 3).