THE EPIDERMIS IN
WOUND HEALING
Published Titles:
Protective Gloves for Occupational Use
Gunh Mellström, J.E. Walhberg, and Howard I. Maibach
Bioengineering of the Skin: Water and the Stratum Corneum
Peter Elsner, Enzo Berardesca, and Howard I. Maibach
Bioengineering of the Skin: Cutaneous Blood Flow and Erythema
Enzo Berardesca, Peter Elsner, and Howard I. Maibach
Bioengineering of the Skin: Methods and Instrumentation
Enzo Berardesca, Peter Elsner, Klaus P. Wilhelm, and Howard I. Maibach
Bioengineering of the Skin: Skin Surface, Imaging, and Analysis
Klaus P. Wilhelm, Peter Elsner, Enzo Berardesca, and Howard I. Maibach
Bioengineering of the Skin: Skin Biomechanics
Peter Elsner, Enzo Berardesca, Klaus-P. Wilhelm, and Howard I. Maibach
Skin Cancer: Mechanisms and Human Relevance
Hasan Mukhtar
Dermatologic Research Techniques
Howard I. Maibach
The Irritant Contact Dermatitis Syndrome
Pieter van der Valk, Pieter Coenrads, and Howard I. Maibach
Human Papillomavirus Infections in Dermatovenereology
Gerd Gross and Geo von Krogh
Contact Urticaria Syndrome
Smita Amin, Arto Lahti, and Howard I. Maibach
Skin Reactions to Drugs
Kirsti Kauppinen, Kristiina Alanko, Matti Hannuksela, and Howard I. Maibach
Dry Skin and Moisturizers: Chemistry and Function
Marie Loden and Howard I. Maibach
Dermatologic Botany

Javier Avalos and Howard I. Maibach
Hand Eczema, Second Edition
Torkil Menné and Howard I. Maibach
Pesticide Dermatoses
Homero Penagos, Michael O’Malley, and Howard I. Maibach
Nickel and the Skin: Absorption, Immunology, Epidemiology, and Metallurgy
Jurij J. Host
´
yneck and Howard I. Maibach
DERMATOLOGY: CLINICAL & BASIC SCIENCE SERIES
Series Editor Howard I. Maibach, M.D.
DERMATOLOGY: CLINICAL & BASIC SCIENCE SERIES
Edited by
David T. Rovee
Howard I. Maibach
THE EPIDERMIS IN
WOUND HEALING
CRC PRESS
Boca Raton London New York Washington, D.C.

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International Standard Book Number 0-8493-1561-1
Library of Congress Card Number 2003055712
Printed in the United States of America 1 2 3 4 5 6 7 8 9 0
Printed on acid-free paper

Library of Congress Cataloging-in-Publication Data

The epidermis in wound healing / edited by David T. Rovee and Howard I. Maibach.
p. ; cm. — (Dermatology)
Includes bibliographical references and index.
ISBN 0-8493-1561-1 (alk. paper)
1. Wound healing. 2. Epidermis. I. Rovee, David T. II. Maibach, Howard I. (Howard
Ira) III. CRC series in dermatology.

[DNLM: 1. Epidermis. 2. Wound Healing. WO 185 E644 2003]
RD94.E65 2003
617.1—dc22 2003055712


Series Preface

Our goal in creating the

Dermatology: Clinical & Basic Science Series

is to present
the insights of experts on emerging applied and experimental techniques and theo-
retical concepts that are, or will be, at the vanguard of dermatology. These books
cover new and exciting multidisciplinary areas of cutaneous research, and we want
them to be the books every physician will use to become acquainted with new
methodologies in skin research. These books can be also given to graduate students
and postdoctoral fellows when they are looking for guidance to start a new line of
research.
The series consists of books that are edited by experts, with chapters written by
the leaders in each particular field. The books are richly illustrated and contain
comprehensive bibliographies. Each chapter provides substantial background mate-
rial relevant to its subject. These books contain detailed tricks of the trade and
information regarding where the methods presented can be safely applied. In addi-
tion, information on where to buy equipment and helpful Web sites for solving both
practical and theoretical problems are included.
We are working with these goals in mind. As the books become available, the
efforts of the publisher, book editors, and individual authors will contribute to the
further development of dermatology research and clinical practice. The extent to
which we achieve this goal will be determined by the utility of these books.


Howard I. Maibach, M.D.


Preface

Just 30 years ago, the book

Epidermal Wound Healing

was published. That collection
of papers from leaders in the field presented an interdisciplinary view of various
aspects of wound healing. The primary focus, while on the epidermis, did not exclude
interaction with other tissues. At the time of that work, little of the emerging data
on wounds was being applied clinically. Today, many of the so-called advanced
wound therapies can be traced back to the ideas presented by the group of contrib-
utors to

Epidermal Wound Healing.

These include the use of film, hydrocolloid, and
gel dressings, which have brought about the acceptance of “moist wound healing”
to prevent dehydration necrosis in the wound and enhance epithelial migration for
early wound closure. The moist environment has also been employed to reduce
inflammation and subsequent scar formation in the dermis. One aspect of these
dressings, which was not predicted by the work in 1972, was their utility in enhancing
autolytic debridement in chronic wounds, such as decubitus, venous, and diabetic
ulcers. Also included in the original publication was the early work on growth factors
and their potential applications to wound therapy. Today, clinicians are able to
employ platelet-derived growth factors (PDGF) and tissue-engineered living skin

products, which deliver an array of other growth factors.
The availability of new biological techniques and a renaissance of interest in
both acute and chronic wound healing have led to a tremendously improved under-
standing of the cellular and chemical complexities of the healing process. We have
begun to appreciate that much of what we have learned based upon acute wound
healing does not always apply to the chronic wound. With this realization, much of
today’s clinical and research practice focuses on decubitus ulcers, venous ulcers,
and diabetic foot ulcers.
Surprisingly, the original text from 1972 remains the only book focused on
epidermal healing and is still frequently cited, even though there have been many
further advances. The purpose of this second book on the topic is to update the
information available on the epidermis, present a selection of the newest findings,
and stimulate original research and development in wound therapy. Our intent is to
focus on biological advances that improve our knowledge and lead to new oppor-
tunities for research and clinical applications in wound healing.

David T. Rovee, Ph.D.
Howard I. Maibach, M.D.


Editors

David T. Rovee, Ph.D.,

began working in the field of wound healing during his
graduate education at Louisiana State University and Brown University, and has
maintained this interest throughout a long career in the pharmaceutical, medical
device, and biotechnology sectors. He has been instrumental in the development of
new approaches in wound care, surgical devices, and dermatologicals while working
in the laboratory and later in managing research and development programs in the

medical industry. He has been the editor of the journal

Wounds: A Compendium of
Clinical Research and Practice

since 1992. Dr. Rovee continues working with
healthcare companies as an outside director and a consultant.

Howard Maibach, M.D.,

is a professor of dermatology at the University of Cali-
fornia, San Francisco and has been a long-term contributor to experimental research
in dermatopharmacology and to clinical research on contact dermatitis, contact
urticaria, and other skin conditions.


Contributors

Magnus S. Ågren

Åagren Dermaconsulting ApS
Humblebaek, Denmark

Oscar M. Alvarez

University Wound Clinics, LLC
Bronx, New York

Leslie Baumann


Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine
Miami, Florida

Jill Holly Bigelman

Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine
Miami, Florida

Laura L. Bolton

ConvaTec
Skillman, New Jersey

Carlos A. Charles

Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine
Miami, Florida

Jeffrey M. Davidson

Department of Pathology

Vanderbilt University School of
Medicine
Nashville, Tennessee

Robert H. Demling

Burn Center
Brigham & Women’s Hospital
Boston, Massachusetts

Kevin Donohue

Department of Dermatology
Roger Williams Medical Center
Providence, Rhode Island

Anna Drosou

Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine
Miami, Florida

William H. Eaglstein

Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine

Miami, Florida

Elof Eriksson

Division of Plastic Surgery
Brigham & Women’s Hospital
Boston, Massachusetts

Vincent Falanga

Department of Dermatology
Roger Williams Medical Center
Providence, Rhode Island

Giovanni Gaggio

Department of Energetics
University of Pisa School of Medicine
Pisa, Italy

Jonathan A. Garlick

Department of Oral Biology and
Pathology
School of Dental Medicine
State University of New York at
Stony Brook
Stony Brook, New York

Mitchel P. Goldman


Department of Dermatology
University of California
La Jolla, California

Monica Halem

Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine
Miami, Florida

Patricia A. Hebda

Children’s Hospital of Pittsburgh
University of Pittsburgh
Pittsburgh, Pennsylvania

Thomas K. Hunt

Department of Surgery
University of California at
San Francisco
San Francisco, California

Robert S. Kirsner

Department of Dermatology and
Cutaneous Surgery

University of Miami School of
Medicine
Miami, Florida

Howard I. Maibach

Department of Dermatology
University of California at
San Francisco School of Medicine
San Francisco, California

Stephen Mandy

Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine
Miami, Florida

Lucy K. Martin

Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine
Miami, Florida

Diego Mastronicola

Department of Dermatology

University of Pisa School of Medicine
Pisa, Italy

Patricia M. Mertz

Department of Dermatology and
Cutaneous Surgery
University of Miami School of
Medicine
Miami, Florida

Holly Rausch

Roger Williams Medical Center
Providence, Rhode Island

Marco Romanelli

Department of Dermatology
University of Pisa School of Medicine
Pisa, Italy

David T. Rovee

The Rovee Group
Cambridge, Massachusetts

Vlad C. Sandulache

University of Pittsburgh School of

Medicine
Pittsburgh, Pennsylvania

Greg Skover

Johnson & Johnson Consumer and
Personal Products Worldwide, Inc.
Skillman, New Jersey

James M. Spencer

Department of Dermatology
The Mount Sinai School of Medicine of
New York University
New York, New York

Tor Svensjo

Department of Surgery
Kristianstad Central Hospital
Kristianstad, Sweden

Stephen Thomas

Surgical Materials Testing Laboratory
Princess of Wales Hospital
Bridgend, South Wales, United Kingdom

Marjana Tomic-Canic


New York University School of
Medicine
New York, New York

Jan Jeroen Vranckx

Division of Plastic and Reconstructive
Surgery
Leuven University Medical School
Leuven, Belgium

Feng Yao

Division of Plastic Surgery
Brigham & Women’s Hospital
Boston, Massachusetts

Hongbo Zhai

Department of Dermatology
University of California at San Francisco
San Francisco, California


Table of Contents

PART I

Cellular and Biochemical Issues


Chapter 1

Human Skin-Equivalent Models of Epidermal Wound Healing:
Tissue Fabrication and Biological Implications 3

Jonathan A. Garlick

Chapter 2

Epidermal Repair and the Chronic Wound 25

Marjana Tomic-Canic, Magnus S. Ågren, and Oscar M. Alvarez

Chapter 3

The Biochemistry of Epidermal Healing 59

Patricia A. Hebda and Vlad C. Sandulache

PART II

Local Environment and Healing

Chapter 4

Moist Wound Healing from Past to Present 89

Laura L. Bolton

Chapter 5


Occlusive and Semipermeable Membranes 103

Hongbo Zhai and Howard I. Maibach

PART III

Quantifying Repair in the Epidermis

Chapter 6

Human and Swine Models of Epidermal Wound Healing 113

Jill Bigelman and Patricia M. Mertz

Chapter 7

Noninvasive Physical Measurements of Wound Healing 125

Marco Romanelli, Diego Mastronicola, and Giovanni Gaggio

Chapter 8

Micro Wound Healing Models 141

Hongbo Zhai and Howard I. Maibach

PART IV

Physical and Chemical Factors Affecting

Repair

Chapter 9

Wound Microbiology and the Use of Antibacterial Agents 155

Robert S. Kirsner, Lucy K. Martin, and Anna Drosou

Chapter 10

Oxygen and Skin Wound Healing 183

Thomas K. Hunt

Chapter 11

Nutrition and Wound Healing 199

Robert H. Demling

Chapter 12

Wound Dressings 215

Stephen Thomas

PART V

New Approaches to Understanding and
Treating Wounds


Chapter 13

Gene Therapy of Wounds 245

Jeffrey M. Davidson

Chapter 14

Wound Bed Preparation 255

Kevin Donohue, Holly Rausch, and Vincent Falanga

Chapter 15

Gene Transfer of Growth Factors for Wound Repair 265

Jan Jeroen Vranckx, Feng Yao, and Elof Eriksson

Chapter 16

Autologous Skin Transplantation 285

Tor Svensjö and Elof Eriksson

Chapter 17

Retinoids and the Epidermis 313

Stephen Mandy, Leslie Baumann, and Monica Halem


Chapter 18

Optimizing Epidermal Regeneration in Facial Skin Following
Aesthetic Procedures 331

Greg Skover, James M. Spencer, and Mitchel P. Goldman

Chapter 19

Active Treatments for Acute and Chronic Wounds 351

Carlos A. Charles and William H. Eaglstein

Index

375