Local Flaps in Facial Reconstruction

LOCAL FLAPS
IN FACIAL
RECONSTRUCTION
Third Edition
Shan R. Baker, MD, FACS
Professor
Facial Plastic and Reconstructive Surgery
Department of Otolayngology—Head and Neck Surgery
University of Michigan
Ann Arbor, Michigan

1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
LOCAL FLAPS IN FACIAL RECONSTRUCTION
ISBN: 978-1-4557-5316-1
Copyright © 2014, 2007, 1995 by Saunders, an imprint of Elsevier Inc.
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Notice
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical
treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in
evaluating and using any information, methods, compounds, or experiments described herein. In
using such information or methods they should be mindful of their own safety and the safety of
others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the
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Previous editions copyrighted 1995, 2007
Library of Congress Cataloging-in-Publication Data
Local flaps in facial reconstruction / [edited by] Shan R. Baker.—Third edition.
    p. ; cm.
  Includes bibliographical references and index.
  ISBN 978-1-4557-5316-1 (hardcover : alk. paper)
  I. Baker, Shan R. editor of compilation.
  [DNLM:  1.  Face—surgery.  2.  Surgical Flaps.  3.  Reconstructive Surgical Procedures.  WE 705]
  RD523
  617.5'2059—dc23
    2013030014
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Last digit is the print number:  9  8  7  6  5  4  3  2  1

To Catherine Belle Baker, Alexander Ray Baker,
and Monica Catherine Baker, and to the thousands
of patients who have trusted me to make their
faces whole

ix
This textbook provides an in-depth discussion of the use
of local flaps for reconstruction of the face, scalp, and
neck. Like the second edition, it is designed to be a
“working man’s” manual for repair of cutaneous defects
of the head and neck, providing practical and effective
methods of reconstructing skin defects of a variety of
sizes, configurations, and locations. It is unique in that
the contributors are from the medical specialties of
otolaryngology, ophthalmology, dermatology, and plastic
surgery. The authors are individuals who I believe have
exceptional knowledge and experience using local flaps in
facial reconstruction. They are some of the most promi­
nent surgeons in their respective specialties.
I am fully cognizant of the political and philosophical
differences among various surgical specialties involved
with reconstructing the face. However, it is important to
set aside any conflicts of interests and disagreements in
order to promote an interchange of ideas and knowledge
that will be both educational to physicians and beneficial
to patients. This textbook represents an example of
mutual interest and cooperation among a diverse group
of surgeons. This is the third edition of a textbook origi­
nally published in 1995 and is printed in three languages.
Although the majority of the illustrations used in this
edition are the same as those appearing in the second
edition, all of the chapters have been upgraded by intro­
ducing new concepts or additional information. In the
majority of chapters, new clinical cases and photographs
have been added or used to replace previous cases and
photographs. As with the second edition, a number of
chapters have been authored by myself. This is due to a
conscious effort on my part to present personal surgical
techniques and my philosophy of using local flaps in
facial reconstruction. To impart my philosophy toward
surgical repair of Mohs defects, I have authored or
co-authored 11 of the 28 chapters comprising this edition.
Neil A. Swanson, MD, a colleague and friend, and I
edited the first edition. Because of my desire to impart a
more personal approach to the current work, I chose to
edit this edition entirely on my own as I did with the
second edition. Although this may have restricted
the diversity of surgical approaches available for discus­
sion, it enables a textbook with a more homogenous nar­
rative and consistent message. Similar to the second
edition, there are videos available, in this case at the
ExpertConsult website. The videos demonstrate the
design and transfer of a multitude of local flaps. Included
in the videos are actual surgical procedures performed in
the operating room. In addition to showing uncompli­
cated cases using simple cutaneous flaps, very complex
defects requiring multiple flaps and grafts are included.
This work represents the culmination of 36 years of
cooperative interaction between me and the dermatologi­
cal surgeons at the University of Michigan. During this
interval, we have shared the care of a few thousand
patients, which I believe was to the patient’s benefit. This
cooperative arrangement facilitated the interchange of
knowledge and experience, which led to a hybrid of surgi­
cal approaches for the repair of facial cutaneous defects.
This cross-fertilization of ideas was a direct benefit to me
and my ability to care for patients and is the source of
my desire to edit this textbook.
This book would not have been possible without
the cooperation of all of the dermatological surgeons in
the Department of Dermatology at the University of
Michigan. For this reason, I express my sincere gratitude
to all of them for their continued support and confidence
in me.
Shan R. Baker, MD, FACS
PREFACE

x
ACKNOWLEDGMENTS
Although many people have indirectly contributed to the
creation of this book, I would like to thank those who
had major roles in assisting me in its preparation.
Foremost, I am grateful to all of my patients who
through their misfortune of being afflicted with skin
cancer have enabled me to learn and perfect reconstruc­
tive surgical techniques. A particular gratitude is offered
to those patients who have allowed me to publish their
photographs in this book.
I would like to thank Deborah DeGuire for assistance
with preparation of the manuscript and Mary Hambright
for her assistance with procuring photographs.
I am grateful to Marcia Stuursma and Deborah
DeGuire for their friendship and support and serving as
my ambassador to patients and colleagues over an interval
that spans nearly my entire professional career.
I am most grateful to Kathy Herman for her unfailing
optimism and unflinching support and for never consid­
ering a task too great or too small to perform. I would
like to thank Lily Wu for providing excellent nursing care
and being such a successful liaison to my patients.
A special thank you goes to James Bruce for his friend­
ship. Mr. Bruce has assisted me for many years by prepar­
ing hundreds of photographs and video clips used in all
of the lectures that I have prepared and books I have
published.
I would like to thank Fred Bobrow for editing the
videos that accompany this book.
I thank Timothy M. Johnson, MD, director of derma­
tological surgery at the University of Michigan, and his
colleagues Darius J. Karimipour, MD; Christopher K.
Bichakjian, MD; Jennifer L. Schwartz, MD; Sandra C.
Paek, MD; Marcus Frohm, MD; and Jeffrey S. Orringer,
MD. Thank you all for referral of your patients through­
out the many years we have been professionally associ­
ated. Without your support and trust, this book would
not have been possible.
I am appreciative of the assistance provided to me in
the filming of the video clips by my fellows Deirdre S.
Leake, MD; Jeffrey S. Moyer, MD; and Wael K. Abdel-
Hamid, MD.
I would like to thank all of the authors of this textbook
for devoting hundreds of hours toward the preparation
of their chapters. The quality of this textbook is directly
related to your contributions.
Shan R. Baker, MD, FACS

xi
CONTRIBUTORS
E. Fred Aguilar III, MD
Professor of Surgery
Michael E. DeBakey Department of Surgery
Division of Plastic Surgery
Baylor College of Medicine
Houston, Texas
Shan R. Baker, MD, FACS
Professor
Facial Plastic and Reconstructive Surgery
Department of Otolayngology—Head and Neck
Surgery
University of Michigan
Ann Arbor, Michigan
Amit D. Bhrany, MD
Assistant Professor
Department of Otolaryngology—Head and Neck
Surgery
University of Washington School of Medicine
Seattle, Washington
Christopher K. Bichakjian, MD
Associate Professor
Department of Dermatology
University of Michigan
Ann Arbor, Michigan
DeWayne T. Bradley, MD
Otolaryngologist
The Polyclinic Northgate
Seattle, Washington
Mack L. Cheney, MD
Director, Massachusetts Eye and Ear Office of Global
Surgery and Health
Kletjian Chair of Global Surgery, Massachusetts Eye
and Ear
Professor of Otolaryngology and Laryngology
Harvard University Medical School
Boston, Massachusetts
Alison B. Durham, MD
Department of Dermatology
University of Michigan Medical School
Ann Arbor, Michigan
Robert G. Fante, MD, FACS
Associate Clinical Professor
Department of Ophthalmology
University of Colorado
Denver, Colorado
John L. Frodel, MD
Geisinger Medical Center
Director, Facial Plastic Surgery
Department of Otolaryngology—Head and Neck
Surgery
Danville, Pennsylvania
Atlanta Medispa and Surgicenter
Atlanta and Marietta, Georgia
Marcus L. Frohm, MD
Assistant Professor
Department of Dermatology, Cutaneous Surgery and
Oncology
University of Michigan
Ann Arbor, Michigan
George Goding Jr., MD
Professor, Department of Otolaryngology
University of Minnesota Medical School
Faculty, Department of Otolaryngology
Hennepin County Medical Center
Minneapolis, Minnesota
Tessa A. Hadlock, MD
Director, Facial Plastic and Reconstructive Surgery
Department of Otolaryngology
Massachusetts Eye and Ear Infirmary and Harvard
Medical School
Boston, Massachusetts
Michael John Hawes, MD, FACS
Clinical Professor of Ophthalmology
University of Colorado Health Sciences Center
Oculoplastic/Facial Surgeon
Porter Memorial Hospital
Denver, Colorado
Marcelo Hochman, MD
Hemangioma and Malformation Treatment Center
Charleston, South Carolina
John F. Hoffmann, MD
Spokane Center for Facial Plastic Surgery
Spokane, Washington
David B. Hom, MD, FACS
Professor, Director, Division of Facial Plastic and
Reconstructive Surgery
Department of Otolaryngology—Head and Neck
Surgery and Dermatology
University of Cincinnati College of Medicine
Medical Director for Facial Trauma
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio

xii
CONTRIBUTORS
Brian S. Jewett, MD
Assistant Professor
Division of Facial Plastic and Reconstructive Surgery
University of Miami Miller School of Medicine
Miami, Florida
Timothy M. Johnson, MD
Lewis and Lillian Becker Professor
University of Michigan Medical School
Ann Arbor, Michigan
Cody A. Koch, MD, PhD
Plastic Surgeon
Koch Facial Plastic Surgery and Spa
West Des Moines, Iowa
Wayne F. Larrabee Jr., MD
Clinical Professor
Department of Otolaryngology—Head and Neck
Surgery
University of Washington
Director, Larrabee Center for Facial Plastic Surgery
Seattle,Washington
Deirdre S. Leake, MD
Facial Plastic Surgeon and Otolaryngologist
Flagler Hospital
St. Augustine, Florida
Stewart Little, MD
Assistant Professor
Department of Otolaryngology
LSU Health Shreveport
Shreveport, Louisiana
Benjamin C. Marcus, MD
Associate Professor of Surgery
Department of Surgery
University of Wisconsin School of Medicine
and Public Health
Madison, Wisconsin
Jeffrey S. Moyer, MD
Associate Professor and Chief, Facial Plastic and
Reconstructive Surgery
Department of Otolaryngology—Head and Neck
Surgery
University of Michigan
Ann Arbor, Michigan
Craig S. Murakami, BS, MD
Clinical Associate Professor
Virginia Mason Medical Center
University of Washington
Seattle, Washington
Sam Naficy, MD
Clinical Assistant Professor
Facial Plastic and Reconstructive Surgery
University of Washington
Seattle, Washington
Stephen S. Park, MD
Professor and vice chair
Department of Otolaryngology
University of Virginia
Charlottesville, Virginia
Sachin S. Pawar, MD
Fellow/Instructor
Facial Plastic and Reconstructive Surgery
Oregon Health and Science University
Portland, Oregon
Vito C. Quatela, MD
Clinical Associate Professor, Otolaryngology
University of Rochester
Staff, Department of Otolaryngology
Strong Memorial Hospital
Staff, Department of Otolaryngology
Unity Hospital Systems
Rochester, New York
Gregory J. Renner, MD
Professor
Department of Otolaryngology—Head and Neck
Surgery
University of Missouri School of Medicine
Columbia, Missouri
Ronald J. Siegle, MD
Clinical Professor of Dermatology
Division of Dermatology
Department of Internal Medicine
The Ohio State University
Columbus, Ohio
Randal W. Swenson, BA, MD
Assistant Clinical Professor
Otolaryngology
University of Utah Health Sciences Center
Salt Lake City, Utah
Jonathan M. Sykes, MD
Professor and Director of Facial Plastic Surgery
Department of Otolaryngology
University of California, Davis
Sacramento, California
Tom D. Wang, MD
Professor and Chief
Division of Facial Plastic and Reconstructive Surgery
Oregon Health and Science University
Portland, Oregon

3
C H A P T E R 1 
ANATOMY OF THE SKIN
Marcus L. Frohm  •  Alison B. Durham  •  Christopher K. Bichakjian  •  Timothy M. Johnson
INTRODUCTION
The skin is a complex organ system that is essential for
all forms of mammalian life. It may be viewed as a double-
layered sheath, cushioned by the underlying subcutane­
ous adipose tissue, that covers the entire surface of the
body. The outer layer of skin, known as the epidermis, is
separated from the inner layer, or dermis, by the base­
ment membrane zone. The dermis is attached to the
subcutaneous adipose tissue and underlying musculature
by fibrous insertions. Important structures, such as epi­
dermal appendages (hair follicles, sebaceous glands, and
sweat glands), nerves, blood vessels, and immunologic
cells, are present in the skin (Fig. 1-1). As an organ
system, the skin has many important physiologic and
immunologic properties: it provides a barrier to the envi­
ronment, regulates body temperature, and serves as an
important component of the immune system.1-3
A complete understanding of anatomy is the corner­
stone of surgery. Moreover, an awareness of cutaneous
anatomy is essential for a full appreciation of the human
body’s functional, social, and aesthetic relationship with
its environment. The purpose of this chapter is to provide
a basic knowledge of the normal anatomy of the skin.
Possession of such knowledge will rebut the allegations
of those who purport that most surgeons cannot tell the
difference between the epidermis and the dermis yet cut
through these layers on a daily basis.
GENERAL CHARACTERISTICS
Skin is highly variable from one person to another and,
within the same individual, from one anatomic region to
another, with differences to be observed in color, texture,
thickness, and content of hair follicles and sebaceous
glands. Skin may be divided into smooth, non–hair-bear­
ing (glabrous) and hair-bearing (nonglabrous) areas,
although it is virtually always hair-bearing. Skin is the
heaviest human organ, weighing approximately 3.8 kg.
The largest organ in surface area, the lung, measures
about 4.2 m2 on expiration; in comparison, the skin mea­
sures approximately 1.7 m2 in surface area. As a tissue,
skin ranks fourth in weight behind muscle, adipose tissue,
and bone.4
Considerable variation in skin thickness and content of
appendages and elastic fibers exists with respect to ana­
tomic region, age, and sex. An appreciation of these varia­
tions is clinically important for understanding wound
healing and aesthetics. These variations play an integral
role in the definition of facial aesthetic regions, boundar­
ies, and junctions. The surgeon must apply knowledge of
these factors to the task of determining the best recon­
structive option during flap or graft surgery. Careful
examination of the skin is essential for making the best
tissue match for aesthetic reconstruction. Discrepancies
in the thickness of skin edges should be observed before
wound closure for exact reapproximation of the edges.
The best donor site for a full-thickness skin graft is deter­
mined by an examination of all potential donor sites with
respect to skin thickness, color, texture, and content of
hair follicles and sebaceous glands. Careful examination
of the skin before surgery may uncover several clues that
could influence the outcome. Individuals with fair skin,
light hair, and blue eyes may develop postoperative scars
that remain pink for an extended period. Persons with
dark skin, hair, and eyes may develop scars that remain
pigmented for a prolonged period after surgery. An assess­
ment of previous scars and keloids should be made. Indi­
viduals with hyperelastic skin features are characterized
by hyperextensibility of the joints (elbows, wrists, and
knees), anterior hooding of the navel, and lax skin
(Figs. 1-2 to 1-4). These individuals are at higher risk for
development of wide scars, permanent railroad tracking
suture marks, hypertrophic scars, and prolonged ery­
thema of the scars lasting up to 1 year, eventually resulting
in a porcelain-colored white scar. Whereas it is also
present in Ehlers-Danlos syndrome, hyperelastic skin is
most often simply a relatively common normal variant
within the population. Patients with common skin condi­
tions, such as atopic dermatitis, psoriasis, and unusually
dry skin, may have high counts of staphylococcal organ­
isms on their skin and thereby increased risk of wound
infections. In essence, basic knowledge of skin anatomy is
something that is applied daily in reconstructive surgery.
EPIDERMIS
The epidermis, the outermost layer of the skin, is a
continually renewing, keratinizing, stratified, squamous
epithelium. All epidermal appendages, including hair fol­
licles, sebaceous glands, and eccrine and apocrine sweat
glands, derive from this layer. The epidermis consists of
four distinct cell types: keratinocytes, melanocytes, Lang­
erhans cells, and Merkel cells. The predominant cell type
is the keratinocyte, which constitutes at least 80% of
epidermal cells. Four clearly defined layers are identified

4
SECTION I  FUNDAMENTALS
in the epidermis (Fig. 1-5): basal layer (stratum germina­
tivum), spinous layer (stratum spinosum), granular layer
(stratum granulosum), and cornified layer (stratum
corneum). The basal layer is the deepest layer in the epi­
dermis. It is composed of a single germinative layer of
columnar-shaped keratinocytes that attach to the base­
ment membrane zone and give rise to the more superficial
epidermal layers. The next layer, the spinous layer, is
several cells thick and composed of polygonal cells with
abundant eosinophilic cytoplasm. Small spiny desmo­
somal attachments between the spinous cells are evident
under light microscopy. As the spinous cells migrate
superficially and differentiate into granular cells, they
become larger and flatter. The granular layer, usually one
to four cells thick, is composed of cells with deeply baso­
philic keratohyalin granules. Further maturation occurs
in the outermost stratum corneum, which is highly vari­
able in thickness. In this layer, keratinocytes lose their
nuclei and flatten to form plates of keratin, which are shed
as “dead skin.” The stratum corneum is thickest on the
palms and soles and thinnest on the eyelids and genitalia.
FIGURE 1-1  ■  Schematic vertical cross section of skin.
Eccrine
sweat duct
Meissner's
corpuscle
Arrector pili
muscle
Eccrine
sweat gland
Hair bulb
Blood vessels
and nerves
Fibroblast
Epidermis
Dermis
(papillary)
Sebaceous
gland
Sympathetic
nerve fibers
Subcutaneous
fat
Apocrine
sweat gland
Hair follicle
Dermis
(reticular)
FIGURE 1-2  ■  Hyperextensibility of elbow in a healthy 28-year-
old woman with hyperelastic skin features.
FIGURE 1-3  ■  Hyperextensibility of wrist in a healthy 36-year-old
woman with hyperelastic skin features.
FIGURE 1-4  ■  Anterior hooding of navel in a healthy 30-year-old
woman with hyperelastic skin features.

1  ANATOMY OF THE SKIN
5
Tyrosinase activity and melanocyte density decrease with
age.7
Langerhans Cells
Langerhans cells are bone marrow–derived, antigen-
processing, and antigen-presenting cells found mainly in
the suprabasal epidermal layers. They are, however, not
unique to the epidermis and are found in other squamous
epithelia and in the normal dermis. In routine histologic
preparations, Langerhans cells are pale-staining cells that
are difficult to identify and more readily demonstrated
with special stains or immunohistochemistry. Like mela­
nocytes, Langerhans cells are characterized by dendritic
processes. The cytoplasm, as seen by electron micros­
copy, contains small racket-shaped structures known as
Birbeck or Langerhans cell granules. Langerhans cells
are responsible for recognizing and presenting antigens
to lymphocytes in the skin and are implicated in the
pathologic mechanism underlying allergic contact der­
matitis and skin allograft reactions. The number of Lang­
erhans cells decreases after ultraviolet irradiation. This
results in a diminished capacity for immune surveillance,
which may play a role in cutaneous carcinogenesis. The
number of Langerhans cells also decreases with age.8
Merkel Cells
Merkel cells are neuroendocrine cells of epidermal origin
that function as slow-adapting mechanoreceptors pri­
marily concerned with touch sensation.9,10 They are
Total epidermal turnover time from the basal layer to the
stratum corneum is approximately 30 days. The thickness
of the epidermis is generally about 0.075 to 0.15 mm. The
epidermis is thin at birth, becomes thicker during puberty
and early adulthood, and thins in the fifth and sixth
decades of life.1,3
Melanocytes
Melanocytes are dendritic, pigment-synthesizing cells of
neural crest origin with clear cytoplasm confined to the
basal layer. The ratio of melanocytes to basal cells ranges
from 1 : 4 on the cheek to 1 : 10 on the limbs. The function
of melanocytes is to produce protective melanin pigment.
Melanin is packaged in the form of melanosomes, which
are transported through stellate dendritic projections to
a group of adjacent keratinocytes in the basal and spinous
layers (epidermal melanin unit). The keratinocytes engulf
the melanosomes and arrange the pigment in an umbrella-
like distribution over the nuclei, protecting them from
potentially harmful ultraviolet irradiation (Fig. 1-6). This
partly explains why people with less pigmentation are at
greater risk for development of cutaneous malignant neo­
plasms, such as basal cell carcinoma, squamous cell carci­
noma, and melanoma.5,6 The number of melanocytes does
not differ between races. The number and size of mela­
nosomes is greater in pigmented skin and accounts for the
darker skin color seen in pigmented persons. In vitiligo,
melanocytes are completely absent. In albinism, melano­
cytes are present but lack the enzyme tyrosinase. Without
tyrosinase, tyrosine cannot be transformed into melanin.
FIGURE 1-5  ■  Layers of epidermis.

Cornified layer
(stratum corneum)
Granular layer
(stratum granulosum)
Spinous layer
(stratum spinosum)
Basal layer
(stratum germinativum)
Dermis

6
SECTION I  FUNDAMENTALS
cell carcinoma, or cutaneous neuroendocrine carcinoma,
most likely arises from epidermal Merkel cells.11
DERMAL-EPIDERMAL JUNCTION
The epidermis is attached to the dermis by a basement
membrane zone known as the dermal-epidermal junction
(Fig. 1-7).12 By light microscopy, the dermal-epidermal
junction is identified as a thin pink band that stains
positive with periodic acid–Schiff stain. This complex
zone provides mechanical support to the epidermis and
acts as a semipenetrable barrier to chemicals and other
predominantly found among basal keratinocytes in areas
of high tactile sensitivity, such as the lips, digits, oral
cavity, and hair follicles. At these sites, Merkel cells often
aggregate in specialized structures, called tactile disks or
touch domes, in close association with peripheral nerve
endings to form the Merkel cell–neurite complex. Merkel
cells, like Langerhans cells, are difficult to identify in
light microscopy without the use of immunohistochemi­
cal markers. Ultrastructurally, Merkel cells are character­
ized by membrane-bound, dense-core granules. These
granules are similar to the neurosecretory granules
found in neurons and contain neurotransmitter-like
substances and markers of neuroendocrine cells. Merkel
FIGURE 1-6  ■  Melanocytes in basal layer (arrows) project
stellate, dendritic processes to surrounding keratino­
cytes in basal and spinous layers (epidermal melanin
unit). Note umbrella-like distribution of melanin pigment
over keratinocyte nuclei.
Melanocyte
Dendritic projections
Melanin pigment
FIGURE 1-7  ■  Dermal-epidermal junction.
{
{
Lamina
lucida
Lamina
densa
Anchoring
fibrils
Basal cell
Plasma
membrane
Basal
keratinocyte
Hemidesmosome
Keratin filaments
Anchoring
filaments

1  ANATOMY OF THE SKIN
7
altered, or destroyed, resulting in dermal-epidermal sep­
aration, such as in epidermolysis bullosa.13
EPIDERMAL APPENDAGES
Hair Follicle
The hair follicle is the main component of a structure
known as the pilosebaceous unit, which also includes the
hair shaft, sebaceous gland, arrector pili muscle, and
sensory end organ (Fig. 1-8). The pilosebaceous unit has
motor and sensory functions and is responsible for the
substances. Keratin filaments within the basal keratino­
cyte condense and attach to an electron-dense plaque
at the inferior aspect of the cell membrane, known as
the hemidesmosome. The hemidesmosomes are firmly
anchored to the underlying lamina densa through con­
necting anchoring filaments in the lamina lucida. The
lamina densa is attached to anchoring plaques in the
underlying dermis by anchoring fibrils and elastic fibers.
Anchoring fibrils, mainly composed of type VII collagen,
are degraded by collagenases and are absent in new scars.
The importance of the dermal-epidermal junction can be
surmised from a variety of inherited and acquired diseases
of the skin in which different components are absent,
FIGURE 1-8  ■  Pilosebaceous unit.
Infundibulum
Isthmus
Inferior
portion
Medulla
Cortex
Cuticle
Huxley's layer
Henle's layer
Outer root sheath
Vitreous membrane
Sebaceous
gland
Arrector pili
muscle
Bulge
Apocrine
sweat gland
Hair bulb
Follicular papilla

8
SECTION I  FUNDAMENTALS
FIGURE 1-9  ■  A, B, Vertical section of normal hair follicle showing distinct concentric layers.
Medulla
Outer
root sheath
Henley's layer
Huxley's layer
Cuticle
INNER
ROOT SHEATH:
Periadnexal
tissue
Dermal-
epidermal
junction
Matrix
Follicular
papilla
Cortex
A
B
production of hair and sebum. On the scalp, the follicular
component is predominant, resulting in thick, dense ter­
minal hair. Fine, thin vellus hair is found on the temples
and forehead. On the nasal tip, the sebaceous component
predominates, and the total structure is sometimes termed
sebaceous follicle. The complete pilosebaceous unit is
absent on the palms, soles, and mucous membranes.
Re-epithelialization of partial-thickness wounds occurs
not only from the wound edges but also from the pilose­
baceous units.
Longitudinally, the hair follicle is divided into three
regions (see Fig. 1-8). The uppermost portion, the infun­
dibulum, extends from the skin surface to the opening of
the sebaceous duct into the follicle. The segment between
the follicular opening of the sebaceous duct and the bulge
is known as the isthmus. The inferior portion lies below
the area of the bulge and includes the lowermost part of
the follicle and the hair bulb. The bulge is a region
enriched with follicular epithelial stem cells and the
insertion site of the arrector pili muscle. This muscle
inserts into the perifollicular connective tissue sheath
around the bulge and extends obliquely and upward into
the papillary dermis. Contraction of the arrector pili
muscle, innervated by sympathetic nerve fibers, makes
the hair “stand up” (goose bumps) as it is pulled from an
oblique to a vertical position, providing a greater thermal
barrier to the skin. Sensory nerves are located around the
isthmus and inferior portion of the hair follicle. These
nerves are stimulated as a touch receptor when the hairs
are touched.
The internal organization of the hair follicle is best
conceptualized as a series of distinct concentric layers
(Fig. 1-9). The most peripheral layer, the outer root
sheath, is contiguous with the epidermis and is lined by
the dermal-epidermal junction. In the infundibulum, the
outer root sheath consists of all layers of the epidermis.
Distal to the follicular opening of the sebaceous duct, the
outer root sheath consists of a markedly vacuolated

1  ANATOMY OF THE SKIN
9
because each follicle functions independently, humans do
not shed hair synchronously. On the human scalp,
approximately 85% of hairs are in anagen, and the average
length of the growing phase is 3 to 4 years. The number
of hair follicles on the scalp is approximately 100,000 in
people with brown or black hair, about 10% greater in
blonds, and 10% less in redheads.
The follicular epithelium in the dermis provides
an additional source of germinative cells for re-
epithelialization of partial-thickness wounds. The follicu­
lar dermal extension of the epidermis also allows
epidermal diseases, such as Bowen’s disease (squamous
cell carcinoma in situ), to extend into the dermis. This
may result in a higher recurrence rate if superficial treat­
ment methods (such as CO2 laser) do not destroy the
follicular downward extension of the disease process.
Sebaceous Glands
Sebaceous glands are unilobular or multilobular struc­
tures that connect to the hair follicle by a squamous
epithelial duct. Each lobule consists of a peripheral
cuboidal or flattened germinative cell layer. These cells
spinous layer due to the presence of glycogen. Next is the
inner root sheath, which consists of three distinct layers:
Henley’s layer, Huxley’s layer, and a cuticle. Innermost is
the hair shaft, which also has three layers: its cuticle, the
cortex that forms the bulk of the hair shaft, and the vari­
able central medulla. The medulla is absent in lanugo and
vellus hairs. The inner root sheath and hair shaft are
derived from a proliferation of germinative cells, known
as the matrix, at the base of the hair follicle. The distal
hair bulb forms an invagination around the follicular
papilla, which is richly vascularized and contains abun­
dant nerve endings.
Hair follicles undergo cycles of growth, involution,
and rest (Fig. 1-10). During the growing phase, or anagen,
matrix keratinocytes in the bulb proliferate rapidly and
produce the growing hair. During the involutional phase,
or catagen, the matrix cells abruptly cease proliferating,
and the lower portion of the hair follicle involutes. In
telogen, the resting phase, the inferior portion of the
follicle is lost, and the follicular papilla comes to rest at
the height of the bulge. The club-shaped telogen hair is
typically shed from the follicle during telogen or the
subsequent anagen. Human hair growth is cyclic, but
FIGURE 1-10  ■  Hair growth cycle proceeding from anagen through catagen to telogen. Growth occurs during longest anagen phase.
Lower portion of hair follicle involutes during catagen. In telogen, inferior portion of follicle is lost and follicular papilla comes to
rest at height of bulge.
Club hair
Arrector pili
muscle
Bulge
Hair bulb
Follicular papilla
Anagen Catagen Telogen

10
SECTION I  FUNDAMENTALS
DERMIS
The dermis is an integrated connective tissue system
between the epidermis and the subcutaneous adipose
tissue that makes up the bulk of the skin. It accommo­
dates nerve and vascular networks, epidermal append­
ages, fibroblasts, macrophages, mast cells, and other
blood-borne cells. The extracellular dermal matrix is
composed primarily of collagen, with lesser amounts of
elastin, and filamentous and amorphous molecules known
as ground substance. The dermis provides the skin its
pliability, elasticity, and tensile strength. It is divided into
the relatively thin, superficial papillary dermis and the
deeper, thicker reticular dermis. There is great regional
variation in thickness of the dermis, ranging from less
than 1 mm on the eyelid to 1.5 mm on the temple,
2.5 mm on the scalp, and more than 4 mm on the back.
The dermis is thin at birth, increases in thickness until
the fourth or fifth decade, and then decreases. Men
usually have a thicker dermis than women do.
Collagen
Collagen is the principal component of the dermis and
accounts for approximately 75% of the dry weight of
skin. Collagen fibers are synthesized by fibroblasts and
provide both tensile strength and elasticity to the skin.
Approximately 85% of dermal collagen is type I collagen,
which is found predominantly as thick broad bands in the
reticular dermis. Type III collagen constitutes roughly
10% of dermal collagen and forms the fine collagen fibers
located primarily in the papillary dermis. Collagen types
IV and VII are located mainly in the basement membrane
zone.14
Collagen fibers are continuously being degraded by
proteolytic enzymes called matrix metalloproteinases,
such as collagenase, and replaced by newly synthesized
fibers. Ultraviolet irradiation induces matrix metallopro­
teinases in the epidermis and dermis, leading to dermal
collagen degradation. This is manifested histologically as
the disorganization of collagen fibrils and clinically as
skin wrinkling in photoaging. Tretinoin inhibits the
induction of matrix metalloproteinases and improves the
appearance of photoaged skin by reducing fine lines and
wrinkles.15,16 It is believed that matrix metalloproteinases
are induced by CO2 laser treatment to degrade photo­
damaged collagen. This degradation is followed by the
formation and deposition of new collagen.17
Elastin
Elastic fibers in the dermis return the skin to its normal
configuration after being stretched or deformed. The
normal fibers are not readily seen on routine histology
without the aid of special elastic tissue stains. Elastic
fibers in the dermis are synthesized primarily by fibro­
blasts. In the papillary dermis, the fibers are thin and
run perpendicular to the skin surface, whereas those
in the reticular dermis are thicker and run parallel to
the skin surface. Like collagen, elastic tissue is in a con­
tinuous state of synthesis and degradation by matrix
give rise to a central, lipid-laden, vacuolated cell popula­
tion with characteristic clear to foamy cytoplasm. The
glands secrete sebum through the sebaceous duct into the
follicle and onto the surface of the skin. Sebum, a complex
lipid mixture, acts as an emollient to the hair and skin
and may have a protective function.
Sebaceous glands enlarge and become functionally
active during puberty. They are found everywhere on the
body, except the palms and soles, and are most abundant
on the face and scalp. Sebum secretion is largely con­
trolled by androgens and is associated with acne. Seba­
ceous glands may enlarge considerably in middle-aged
and elderly persons, resulting in benign yellow papular
lesions known as sebaceous hyperplasia. In certain loca­
tions, sebaceous glands arise independently and are not
associated with a hair follicle, such as the vermilion
border of the lip (Fordyce spots) and the eyelids (meibo­
mian glands).
Eccrine Sweat Glands
Eccrine sweat glands are found everywhere on the skin,
except the mucous membranes, and are most abundant
on the palms, soles, axillae, and forehead. The eccrine
sweat unit is composed of two segments, a coiled secre­
tory gland and a duct. The secretory gland is located in
the deep reticular dermis or the junction between the
dermis and subcutaneous adipose tissue. The glandular
lumen is lined by an inner layer of secretory cells and an
outer layer of contractile myoepithelial cells. The dermal
duct ascends upward to the coiled intraepidermal duct
(acrosyringium), which opens directly to the skin surface.
The eccrine sweat gland is innervated by cholinergic
nerve fibers, which are stimulated by thermal, mental,
and gustatory stimuli. A person can perspire as much as
several liters per hour and 10 liters per day. The duct
modifies the composition of sweat, which consists of
water, sodium, chloride, potassium, urea, and lactate.
Apocrine Sweat Glands
Apocrine sweat glands are generally confined to the
axillae, areolae, perineum, eyelids (Moll’s glands), and
external auditory canal (ceruminous glands). They do not
become functional until just before puberty. Apocrine
sweat glands respond to emotive stimuli by adrenergic
innervation. They produce an odorless secretion, which
requires bacterial action for odor production. Various
functions including odiferous roles as sexual attractants
and territorial markers have been attributed to apocrine
glands.
The apocrine sweat unit consists of a secretory gland
and a duct. The secretory gland is larger than its eccrine
counterpart and lies in the deep reticular dermis or sub­
cutaneous adipose tissue. It consists of an outer layer of
myoepithelial cells and an inner layer of columnar or
cuboidal eosinophilic cells. The inner layer of cells
appears to secrete droplets into the lumen by decapita­
tion secretion, which can be seen by light microscopy.
The apocrine duct ascends upward through the dermis
and connects to the infundibulum of the hair follicle
superior to the sebaceous duct.

1  ANATOMY OF THE SKIN
11
mechanical creep. Mechanical creep plays a role in the
physiologic factors of immediate intraoperative tissue
expansion.19
Cellular Component
Fibroblasts constitute the main cellular component of the
dermis and synthesize collagen, elastin, and ground sub­
stance. They are abundant in the papillary dermis and
scant in the reticular dermis. The function of this meta­
bolically dynamic cell is to provide a structural extracel­
lular matrix framework and to promote interaction
between epidermis and dermis. Fibroblasts play a major
role in wound healing and behave like a contractile cell
during wound contraction. The number of fibroblasts in
the skin decreases with age.
Monocytes, macrophages, and dermal dendrocytes
constitute the phagocytic cells in the dermis. Mast cells
are specialized secretory cells present in greatest density
in the papillary dermis, near the basement membrane
zone, and around epidermal appendages, blood vessels,
metalloproteinases such as elastase. Elastic tissue is com­
posed of a protein elastin and a microfibrillar matrix that
contains fibrillin, a glycoprotein, and other components.
The amino acids desmosine and isodesmosine are unique
to elastin.18
Ground Substance
Ground substance surrounds and embeds the fibrous
components of the dermis and is found in all tissues of
the body. It consists predominantly of proteoglycans
(such as chondroitin sulfate and dermatan sulfate), gly­
cosaminoglycans (such as hyaluronic acid), and filamen­
tous glycoproteins (such as fibronectin). In the dermis,
ground substance is primarily synthesized by fibroblasts
and appears as fine mucinous stroma on routine histo­
logic stains. Ground substance plays a role in skin hydra­
tion and helps preserve the tensile elasticity of compressed
skin by redistributing the pressure forces. Relative dehy­
dration in the skin due to displacement of ground sub­
stance is partly responsible for the phenomenon termed
FIGURE 1-11  ■  Vasculature of skin. Superficial and deep vascular plexuses provide nourishment to skin and epidermal appendages.
Epidermis
Capillary
loop system
Papillary dermis
Superficial
vascular
plexus
Reticular
dermis
Deep vascular
plexus
Subcutaneous
fat
Subcutaneous
arteries

12
SECTION I  FUNDAMENTALS
present in the dermis (Fig. 1-11).21 At the junction of the
dermis and subcutaneous adipose tissue lays the deep
vascular plexus, which receives its vascular supply from
musculocutaneous arteries perforating the subcutaneous
adipose tissue. Arterioles from the deep vascular plexus
supply the epidermal appendages and the superficial vas­
cular plexus. The superficial vascular plexus lies in the
superficial aspect of the reticular dermis and gives rise to
a rich capillary loop system in the papillary dermis. This
capillary loop system abuts the epidermis and provides it
with nutrients by diffusion. The dermis also contains a
lymphatic system that resembles the vascular plexuses.
and nerves. Mast cells are the primary effector cells in the
onset of an allergic reaction and may be important in
initiating the repair of damaged skin.20
Vasculature
Soft tissue surgery on the head and neck usually heals
particularly well because of a rich vascular supply. Most
of the blood flow in the skin is directed toward the more
metabolically active components, namely, the epidermis,
the follicular papillae, and the epidermal appendages. Two
vascular plexuses connected by communicating vessels are
FIGURE 1-12  ■  Nerve supply of skin.
Merkel cell–
neurite complex
Meissner's
corpuscles
Pacinian
corpuscles
Efferent
nerves
Free nerve
endings

1  ANATOMY OF THE SKIN
13
4. Goldsmith LA. My organ is bigger than your organ. Arch Dermatol
1990;126:301.
5. Lens MB, Dawes M. Global perspectives of contemporary epide­
miological trends of cutaneous malignant melanoma. Br J Derma­
tol 2004;150:179.
6. Lock-Andersen J, Drzewiecki KT, Wulf HC. Eye and hair colour,
skin type and constitutive skin pigmentation as risk factors for basal
cell carcinoma and cutaneous malignant melanoma. A Danish case-
control study. Acta Derm Venereol 1999;79:74.
7. Yaar M, Gilchrest BA. Ageing and photoageing of keratinocytes
and melanocytes. Clin Exp Dermatol 2001;26:583.
8. Grewe M. Chronological ageing and photoageing of dendritic
cells. Clin Exp Dermatol 2001;26:608.
9. Morrison KM, Miesegaes GR, Lumpkin EA, et al. Mammalian
Merkel cells are descended from the epidermal lineage. Dev Biol
2009;335:76.
10. Van Keymeulen A, Mascre G, Youseff KK, et al. Epidermal pro­
genitors give rise to Merkel cells during embryonic development
and adult homeostasis. J Cell Biol 2009;187:91.
11. Bichakjian CK, Lowe L, Lao CD, et al. Merkel cell carcinoma:
critical review with guidelines for multidisciplinary management.
Cancer 2007;110:1.
12. Burgeson RE, Christiano AM. The dermal-epidermal junction.
Curr Opin Cell Biol 1997;9:651.
13. Uitto J, Pulkkinen L. Molecular genetics of heritable blistering
disorders. Arch Dermatol 2001;137:1458.
14. Burgeson RE, Nimni ME. Collagen types. Molecular structure and
tissue distribution. Clin Orthop 1992;282:250.
15. Fisher GJ, Wang ZQ, Datta SC, et al. Pathophysiology of prema­
ture skin aging induced by ultraviolet light. N Engl J Med
1997;337:1419.
16. Fligiel SE, Varani J, Datta SC, et al. Collagen degradation in aged/
photodamaged skin in vivo and after exposure to matrix
metalloproteinase-1 in vitro. J Invest Dermatol 2003;120:842.
17. Orringer JS, Kang S, Johnson TM, et al. Connective tissue remod­
eling induced by carbon dioxide laser resurfacing of photodamaged
human skin. Arch Dermatol 2004;140:1326.
18. Christiano AM, Uitto J. Molecular pathology of the elastic fibers.
J Invest Dermatol 1994;103:53S.
19. Johnson TM, Brown MD, Sullivan MJ, et al. Immediate intraop­
erative tissue expansion. J Am Acad Dermatol 1990;22:283.
20. Church MK, Clough GF. Human skin mast cells: in vitro and in
vivo studies. Ann Allergy Asthma Immunol 1999;83:471.
21. Braverman IM. The cutaneous microcirculation. J Investig Derma­
tol Symp Proc 2000;5:3.
22. Johansson O. The innervation of the human epidermis. J Neurol
Sci 1995;130:228.
Nerve Supply
A rich cutaneous nerve supply consisting of free nerve
endings and specialized corpuscular receptors permits the
body to accurately interpret the continuous bombard­
ment of stimuli received from the external environment
(Fig. 1-12).22 Temperatures, pain, and itch are transmit­
ted by both myelinated and nonmyelinated free nerve
endings particularly common in the papillary dermis just
beneath the epidermis. Specialized receptors include
Meissner’s and pacinian corpuscles. Meissner’s corpuscles
mediate fine touch sensation and are predominantly
found in the papillary dermis of the hands, feet, lips, and
forearms. Pacinian corpuscles are involved in the appre­
ciation of deep pressure and vibration. They are primarily
found in the deep dermis and subcutaneous adipose tissue
of the palms, soles, dorsal surfaces of digits, and genitalia.
Efferent nerves in the dermis innervate blood vessels and
appendageal structures and regulate their function.
SUMMARY
A basic knowledge of skin anatomy is required to fully
understand skin tissue match, tissue stretch, skin thick­
ness and elasticity, wound contraction, and other con­
cepts used on a daily basis by surgeons who perform local
flap reconstructive surgery.
REFERENCES
1. Chug DH, Hake AR, Holbrook K, et al. The structure and devel­
opment of skin. In: Freedberg IM, Eisen AZ, Wolff K, et al, editors.
Fitzpatrick’s dermatology in general medicine. 6th ed. New York:
McGraw-Hill; 2003.
2. White CF, Bigby M, Sangüeza OP. What is normal skin? In: Arndt
KA, Leboit PE, Robinson JK, et al, editors. Cutaneous medicine
and surgery—an integrated program in dermatology. Philadelphia:
WB Saunders; 1996.
3. McKee PH. Pathology of the skin with clinical correlations.
London: Mosby-Wolfe; 1996.

14
C H A P T E R 2 
SKIN FLAP PHYSIOLOGY
George Goding Jr.  •  David B. Hom
INTRODUCTION
The creation of a cutaneous flap applies specific stresses
to otherwise normal skin. These stresses include local
tissue trauma and reduced neurovascular supply to the
affected tissue. The extent to which skin can survive these
injuries is a reflection of the anatomy and physiology of
skin as well as the cutaneous response to injury. Knowl­
edge of these principles has led to improved skin flap
survival by means of flap design and flap delay. Increasing
cutaneous flap survival by minimizing the deleterious
physiologic effects of flap transposition is an area of active
research.
PHYSIOLOGIC CHARACTERISTICS OF SKIN
The skin serves as a sensory and protective organ. The
thick epidermal layers are largely impermeable to gases
and to most liquids. Because of this, many agents that
could result in beneficial effects are ineffective when they
are applied topically to intact skin. Preservation of sensa­
tion in transferred cutaneous flaps is desirable, but its
effect on the physiology of flaps is unclear.
The blood supply to the skin serves two important
functions. It provides nutritional support and a thermo­
regulatory mechanism for the body. Primarily because of
its thermoregulatory function, the rate of blood flow
through the skin is one of the most variable in the body.
Under ordinary skin temperatures, the amount of blood
flowing through the skin (0.25 L/m2 of body surface area)
is approximately 10 times the flow required for nutri­
tional support.1 Blood flow can increase up to seven times
this value with maximal vasodilation. When the body is
exposed to extreme cold, blood flow can be reduced to
levels that are marginal for cutaneous nutrition.
The nutrient capillary network in the reticular dermis
and the arteriovenous shunts in the more superficial pap­
illary dermis2 perform the two functions of the cutaneous
circulation. The amount of blood flow to the skin depends
ultimately on arteriolar pressure and flow. Under condi­
tions of adequate systemic vascular pressure, however,
arterioles act as preshunt and precapillary sphincters that
regulate the flow through each vascular network.3
The sphincters in the two vascular systems respond to
different stimuli (Fig. 2-1). The precapillary sphincter,
which controls the amount of nutritive4 blood flow to the
skin, responds to local hypoxemia and increased meta­
bolic byproducts by dilation.5 Under these conditions,
the blood flow is increased (reactive hyperemia being
an example). The preshunt sphincters are involved in
regulating the changes in blood flow that affect thermo­
regulation and systemic blood pressure.6 Release of nor­
epinephrine by the postganglionic sympathetic fibers
results in contraction of the preshunt sphincters. This
diverts blood away from the skin surface, where heat
loss can occur. With increased body temperature, the
sympathetic vasoconstrictor impulses decrease, allowing
increased blood flow to the skin.4
Vasodilation can also occur with excessive body tem­
perature. Local release of acetylcholine by sympathetic
nerve fibers may cause vasodilation by directly affecting
vasodilator fibers or acting through the release of the
potent vasodilator bradykinin from the sweat glands. The
cutaneous circulation is also extremely sensitive to circu­
lating norepinephrine and epinephrine. Even in areas of
skin that have lost their sympathetic innervation, a mass
discharge of the sympathetic system will still result in
intense vasoconstriction in the skin.
NEUROVASCULAR SUPPLY TO LOCAL
SKIN FLAPS
Blood vessels travel by one of two main routes to termi­
nate in the cutaneous circulation. Musculocutaneous
arteries pass through the overlying muscle to which they
provide nutrition; septocutaneous arteries (also referred
to as direct cutaneous arteries) travel through fascial
septa, which divide the muscle segments (Fig. 2-2).
The cutaneous portion of septocutaneous arteries
typically runs parallel to the skin surface, providing nutri­
tion to a large area of skin. Septocutaneous arteries typi­
cally have a pair of veins accompanying them and run
above the superficial muscular fascia. The more common
musculocutaneous arteries leave the muscle and enter the
subcutaneous tissue to supply a smaller region of skin.
Septocutaneous and musculocutaneous arteries empty
into a diffuse interconnecting vascular network of dermal
and subdermal plexuses. This network provides a redun­
dancy in the vascular supply to the skin. A collateral blood
supply supports the vascular territory of each musculo­
cutaneous artery. Lymphatic vessels form a plexus running
parallel and deep to the network of blood capillaries. The
lymphatic capillaries end in blind sacs and conduct extra­
cellular fluid back into the bloodstream.
The neural supply to the skin originates from both
sensory nerves and sympathetic nerves. The sensory

2  SKIN FLAP PHYSIOLOGY
15
should not imply that a wider flap would extend survival
length.7
Arterial Cutaneous Flaps
Arterial cutaneous flaps (also called axial pattern flaps and
perforator flaps) typically have an improved survival
length relative to random cutaneous flaps.8 This advan­
tage results from the incorporation of a septocutaneous
artery within the longitudinal axis. An island flap is an
arterial flap with a pedicle consisting of nutrient vessels
without the overlying skin. Island flaps can be useful to
increase flexibility and to reduce pedicle bulk in certain
reconstructive procedures.
Use of arterial cutaneous flaps is limited by the avail­
ability of direct cutaneous arteries. An example of an
arterial cutaneous flap used in facial reconstruction is the
paramedian forehead flap based on the supratrochlear
artery.
The surviving length of arterial flaps is related to length
of the included septocutaneous artery. Survival beyond
the arterial portion of the flap is based on the subdermal
plexus and is essentially a random cutaneous extension of
the flap. Flap necrosis secondary to ischemia can be said
to occur only in the random portion of the flap (destruc­
tion of the arterial pedicle making the entire flap random).
Preoperative imaging with computed tomographic angi­
ography to evaluate perforator distribution9 as well as the
nerves are distributed in segmental fashion, forming
dermatomes, and participate in the skin’s protective func­
tion. The postganglionic terminals of cutaneous sympa­
thetic nerves contain the neurotransmitter nor­epinephrine
and are found in the area of cutaneous arterioles.4
VASCULAR DESIGN OF COMMON LOCAL
SKIN FLAPS IN THE HEAD AND NECK
The vascular supply to a flap is critical to its survival and
is the basis of one classification system of flaps (Fig. 2-3).
Local flaps in the head and neck are primarily random or
arterial cutaneous.
Random Cutaneous Flaps
The blood supply to a random cutaneous flap is derived
from musculocutaneous arteries near the base of the flap.
Blood is delivered to the tip of the flap by the intercon­
necting subdermal plexus. The random cutaneous flap is
commonly used in local flap reconstruction and can be
rotated, transposed, advanced, or tubed.
Length-to-width ratios of random cutaneous flaps
have been recommended for various areas of the body.
These differences reflect a regional variation of the
neurovascular supply to the skin. Such a description can
serve as a guide in designing random cutaneous flaps but
FIGURE 2-1  ■  Precapillary (▲) and preshunt (■) sphincters in skin. The precapillary sphincter regulates nutritive blood flow to skin
and responds to locally produced stimuli. The preshunt sphincter is involved in thermoregulation and is affected by sympathetic
stimuli from the central nervous system.
VEIN
ARTERY
Epidermis
Dermis
Subcutaneous fat
Muscle

16
SECTION I  FUNDAMENTALS
overlying the vascular pedicle is usually adequate. In
random flaps or random extensions of flaps, the decrease
in perfusion pressure becomes more pronounced with
increasing distance from the base of the flap.11 When
perfusion is reduced in one area of a random flap, the
adjacent vascular territories supplied by a separate perfo­
rating vessel can provide a low-pressure blood supply
through the subdermal plexus (Fig. 2-4). Because the
nutritional requirements of skin are relatively low, a
number of vascular territories can be compromised before
necrosis will result.
The survival length of the random portion of the flap
depends on the physical properties of the supplying
vessels (intravascular resistance) and the perfusion pres­
sure.11 When the perfusion pressure drops below the
critical closing pressure of the arterioles in the subdermal
plexus, nutritional blood flow ceases and flap necrosis
occurs. In the past, random cutaneous flaps were often
designed relative to a desired length-to-width ratio, a
wider base being needed to successfully transfer a longer
flap. The wider random flap includes only additional
vessels with the same perfusion pressure. The relation­
ship between perfusion pressure and critical closing pres­
sure is not altered, and no change in survival length
occurs7 (Fig. 2-5).
subcutaneous arterial pattern10 can further increase the
usefulness of these flaps.
PHYSIOLOGIC CHANGES AFTER SKIN
FLAP ELEVATION
A number of changes detrimental to skin survival occur
when a cutaneous flap is created. That flap survival occurs
at all is a testimony to the minimal nutritional require­
ments of skin. The primary insult affecting flap survival
is impaired vascular supply and the resultant ischemia. In
the presence of adequate blood flow, complete flap sur­
vival occurs. Nerve section and inflammation influence
flap survival primarily by affecting blood flow. The for­
mation of new vascular channels between the transposed
flap and the recipient bed also influences flap survival.
Impairment of Vascular Supply
Partial interruption of the vascular supply to the skin is
the most obvious and critical change that occurs with
elevation of a cutaneous flap. This interruption results in
a local decrease in perfusion pressure to the skin. In arte­
rial or myocutaneous flaps, the blood supply to the skin
FIGURE 2-2  ■  Depiction of varying pathways to skin that defines musculocutaneous (MC) and septocutaneous (SC) arteries.
Skin
Subcutaneous
tissue
Fascia
Muscle
MC
SC

2  SKIN FLAP PHYSIOLOGY
17
During revascularization, vascular endothelial cells
play a major role in the formation of new vessels. Nor­
mally, endothelial cells are in a quiescent state. However,
when they are stimulated by angiogenic growth factors,
these cells can dramatically proliferate. This normally
occurs only under certain conditions, such as wound
healing and ovulation.
Beginning with an angiogenic stimulus, the angio­
genic process involves a number of discrete yet overlying
steps (Fig. 2-6). Initially, the vessels become dilated and
permeable with retraction of the endothelial cells and a
decrease in endothelial junctions. The basement mem­
brane is then dissolved by proteases, and the endothelial
cells migrate from the vascular wall toward the angio­
genic stimulus. Behind the leading front of migrating
endothelial cells, endothelial cell replication begins,
forming a capillary sprout that elongates toward the
Myers has emphasized that “fresh flaps are always both
viable and ischemic.”12 Depending on the degree of isch­
emia and the amount of time before recovery of nutrient
blood flow, the flap will either die or recover. In the pig
model, arterial and random flaps can tolerate an average
of 13 hours of total avascularity and remain viable.13 In
flaps with reduced perfusion, this time is probably much
longer.
In surviving flaps, blood flow gradually increases. If
the flap is in a favorable recipient site, a fibrin layer forms
within the first 2 days. Neovascularization of the flap
begins 3 to 7 days after flap transposition. Early neovas­
cularization has been detected at 4 days in the pig and
rabbit models14 and at 3 days in the rat model.15 Revas­
cularization adequate for division of the flap pedicle has
been demonstrated by 7 days in animal models and
humans.14,16
FIGURE 2-3  ■  Classification of skin flaps based on vascular supply. A, Random. B, Arterial cutaneous. C, Fasciocutaneous.
D, Musculocutaneous.
Epidermis/
dermis
Subcutaneous
tissue
Fascia
Muscle
A
B
C
D

18
SECTION I  FUNDAMENTALS
however, to preserve venous outflow in flaps pedicled
solely on the feeding vessels.
Impairment of lymphatic drainage with flap elevation
also occurs. Reduction of the cutaneous lymphatic drain­
age results in an increase in interstitial fluid pressure that
is compounded by increased leakage of intravascular
protein associated with inflammation. The resulting
edema can decrease capillary perfusion by increasing the
intravascular resistance.
Nerve Section
Both cutaneous and sympathetic nerves are severed in the
process of flap elevation. Denervation of a skin flap post­
pones neovascularization of the skin flap. Whereas loss
of sensation may limit the usefulness of the flap after
transfer, adrenergic denervation has implications for flap
survival. When a sympathetic nerve is divided, catechol­
amines are released from the nerve terminal and the
mechanism for catecholamine reuptake is eliminated.22 A
local “hyperadrenergic state” develops that produces
vasoconstriction mediated by alpha-adrenergic receptors
in the cutaneous vasculature. In addition, severe sympa­
thetic denervation contributes to the production of
oxygen free radicals, which may exert their inhibitory
effects on neovascularization.23
The vasoconstricting effect of sympathectomy further
reduces the total flap blood flow24 that has already been
diminished by division of supplying vessels. This nega­
tively affects the ratio of perfusion pressure to the critical
closing pressure of the arterioles in the subdermal plexus.
A greater proportion of the distal flap is excluded from
the blood supply and necrosis becomes more likely. The
stored transmitter is depleted within 24 to 48 hours,25 and
blood flow increases as the concentration of norepineph­
rine declines. In critical areas of the flap, however, the
time to recovery of nutrient blood flow may be delayed
sufficiently to produce additional necrosis.
angiogenic source. The nearby capillary sprouts then
anastomose to each other, forming capillary loops. As
capillary loops and sprouts continue, the loops become
patent, forming newly formed blood vessels. These blood
vessels differentiate and lay down basement membrane
consisting of type IV collagen, laminin, and proteogly­
cans. Pericytes and fibroblasts then migrate to the capil­
lary loop sites.17
With the continued presence or absence of the angio­
genic stimulus, substantial remodeling, regression, and
rearrangement of the new capillaries occur.17 Some capil­
laries join preexisting flap vessels (inosculation), but the
majority of revascularization appears to involve direct
ingrowth of recipient vessels into the flap18 (Fig. 2-7).
New capillaries can grow toward an angiogenic source at
a mean rate of 0.2 mm/day. When the angiogenic stimu­
lus is discontinued, the capillary vessels regress and even­
tually disappear during a period of weeks. Angiogenic
growth factors can stimulate capillary growth over dis­
tances of 2 to 5 mm.19
To prevent an uncontrollable cascade of neovascular­
ization, mechanisms to inhibit angiogenesis are believed
to exist. Evidence suggests that pericytes can suppress
endothelial growth by direct contact.20 Thus, the physi­
ologic response of angiogenesis may be analogous to the
blood coagulation pathway that must be maintained at a
constant steady state of control. In soft tissue wound
repair, macrophages, lymphocytes, mast cells, and plate­
lets are involved in releasing various factors that modu­
late angiogenesis.
The venous outflow from the skin is also impaired
with flap elevation. Venous flow can occur through the
subdermal plexus or by venous channels that accompany
the feeding artery in the pedicle. Complete venous occlu­
sion in the early period after elevation may be more
damaging to flap survival than inadequate arterial supply.21
Fortunately, the subdermal plexus alone is often adequate
to provide sufficient venous outflow. Care must be taken,
FIGURE 2-4  ■  Vascular territories in skin flap. Multiple perforating vessels exist and are interconnected at the periphery of their vas­
cular territory. When vessels are cut, blood supply can be replaced from nearby perforating vessels and tissue necrosis does not
occur.

2  SKIN FLAP PHYSIOLOGY
19
created during flap elevation, however, may have delete­
rious effects due to the resultant edema formation.
The action of the primary mediators of the inflamma­
tory response (histamine, serotonin, and kinins) is short-
lived. After kinin formation and in the presence of
complement, prostaglandins are synthesized by injured
cells. Prostaglandins play an important role in the later
stages of the inflammatory reaction while simultaneously
initiating the early phases of injury repair.
Prostaglandins are derived from essential fatty acids
that are incorporated in membrane phospholipids (Fig.
2-8). Activation of phospholipases results in the
Inflammation and Prostaglandins
The surgical trauma associated with an acutely raised flap
results in an inflammatory response. Histamine, sero­
tonin, and kinins are released into the extracellular com­
partment after flap elevation, increasing the permeability
of the microcirculation. The result is an increase in the
concentration of proteins and cells within the extracel­
lular space. The presence of nonbacterial inflammation
beginning a few days before flap elevation has been shown
to improve flap survival.26,27 This is presumably the result
of an increase in local blood flow. The inflammation
FIGURE 2-5  ■  Fallacy of length-to-width ratio. Slope of decreasing perfusion pressure versus flap length does not change with incor­
poration of additional vessels (flap A versus flap B) with same perfusion pressure. Flap necrosis occurs when perfusion pressure
falls below critical closing pressure of capillary bed.
Low
mmHg
Capillary perfusion
pressure
Critical closing pressure
Proximal
Distal
Location along flap
Flap survival Flap necrosis
High
B
A

20
SECTION I  FUNDAMENTALS
in resistance is seen in cutaneous arteries, arterioles, and
venules in the presence of PGF2α.29
The synthesis of prostaglandins and thromboxane can
be altered by pharmacologic manipulation. The action of
phospholipase A2 can be inhibited by drugs that reduce
the availability of calcium. Glucocorticoids also affect
phospholipase A2 activity by inducing the synthesis of a
protein that inhibits the enzyme.30 Aspirin and other
nonsteroidal anti-inflammatory medications interfere
with the cyclooxygenase enzyme, inhibiting the synthesis
of PGH2.
Prostacyclin levels were found to peak 7 days after
elevation of a porcine flank flap.1 Elevation of a bipedi­
cled rat dorsal flap resulted in elevated levels of PGE2,
PGF2α, and TxB2, with a return to nearly normal levels
by day 7. Conversion to a single pedicle flap (“delay”)
resulted in a blunted production of thromboxane and an
elevated PGE2 level. Elevation of an acute flap in the
production of prostaglandin H2 (PGH2) by cyclooxygen­
ase. Prostaglandin E1 (PGE1) and prostaglandin E2
(PGE2) can be synthesized from PGH2 by isomerases in
the vascular endothelium. Both PGE1 and PGE2 produce
vasodilation. Prostaglandin D2 (PGD2) is also formed by
an isomerase reaction and is the principal cyclooxygenase
product of the mast cell. Its effects on the cutaneous
microvasculature are similar to those of PGE1. Prostacy­
clin (PGI2) is a vasodilating agent and inhibitor of platelet
aggregation that is derived from PGH2 through the
action of prostacyclin synthase. In the skin, PGI2 is
primarily produced in the endothelial cells of blood
vessels.1,28
Thromboxane synthetase converts PGH2 into throm­
boxane A2 (TxA2) and is primarily located in the platelets.
Its effects include vessel constriction and promotion of
platelet aggregation. Prostaglandin F2α (PGF2α) is derived
from PGH2 by a reductase reaction. A marked increase
FIGURE 2-6  ■  Steps in angiogenesis. A, Initial stimulus with retraction of endothelial cells and thinning of basement membrane.
B, Migration of endothelial cells and formation of capillary sprout. C, Formation of capillary loops, which become patent to form
new blood vessels.
Angiogenic
stimulus
Angiogenic
stimulus
Angiogenic
stimulus
Sprout
Migrating cells
A
B
C
FIGURE 2-7  ■  Cross section of flap demonstrating direct ingrowth (A) versus inosculation (B).
A
B

2  SKIN FLAP PHYSIOLOGY
21
FIGURE 2-8  ■  Synthesis of prostaglandins and thromboxanes and their general effects in cutaneous circulation.
Essential fatty acids
Membrane phospholipids
Phospholipase A
Arachidonic acid
Cyclooxygenase
PGG
PGH
Thromboxane
synthetase
Prostacyclin
synthase
PGI
Glucocorticoids
Ca blockers
ASA
nonsteroidals
6-keto-PGF
isomerase
isomerase
reductase
TxA
TxB
PGE PGD PGF
reductase
Vasodilator,
inhibits platelet aggregation
Vasoconstrictor,
promotes platelet aggregation
2
2
2
2
2
2α
1α
2
2
2
2+
same model showed an elevation of PGE2, PGF2α, and
TxB2 that was greater and more prolonged than with
surgical delay.31 Prostaglandins clearly play a role in the
inflammatory response after flap surgery. Whether these
changes in prostaglandin levels represent a cause or a side
effect of the observed phenomenon remains to be
demonstrated.
Reperfusion (Free Radicals)
Return of blood flow to a flap that is ischemic as a result
of excessive release of norepinephrine occurs in approxi­
mately 12 hours. With norepinephrine depletion and
continued inflammatory response, blood flow can reach a
maximum at 24 hours.24 When oxygen becomes available
with reperfusion, an additional menace to flap survival is
produced, the free radical. This byproduct of reperfusion
can cause damage at both the cellular and subcellular
levels,32 contributing to postischemic tissue necrosis.
Free radicals are extremely reactive compounds
because of an unpaired electron in their outer orbitals.
Oxygen free radicals are formed by the sequential univa­
lent reduction of molecular oxygen. The superoxide
anion radical (O2−) is formed by the addition of a single
electron to molecular oxygen. Superoxide is a byproduct
of adenosine triphosphate production in the mitochon­
dria and other oxidation reduction reactions.32 Polymor­
phonuclear cells are a second source of superoxide radicals
that are released in response to bacterial inflammation.
A major source of free radicals in ischemic tissue is the
enzyme xanthine oxidase33 (Fig. 2-9). With ischemia,
high-energy phosphate compounds are converted to
hypoxanthine that accumulates in the tissues. When
oxygen becomes available with reperfusion, xanthine
oxidase catalyzes the conversion of hypoxanthine into
uric acid, producing superoxide in the process. This reac­
tion is an important mechanism in ischemic tissue injury
in skin flaps.34 The administration of exogenous vascular
endothelial growth factor (VEGF) could protect flaps
from ischemia-reperfusion injury through the regulation
of proinflammatory cytokines and the inhibition of cyto­
toxic nitric oxide production.35
WOUND HEALING
The acute physiologic consequences of flap creation
affecting blood flow are of primary importance in

22
SECTION I  FUNDAMENTALS
ATTEMPTS TO ALTER SKIN FLAP VIABILITY
Kerrigan36 outlined extrinsic and intrinsic causes of skin
flap failure. Extrinsic reasons for flap necrosis are those
not resulting from the design of the raised flap. Examples
include systemic hypotension, infection, and pedicle
compression. These factors can often be overcome in the
clinical situation. The primary intrinsic factor affecting
flap survival is inadequate blood flow. Numerous experi­
mental attempts have been made to influence flap micro­
circulation or to decrease the deleterious effects of
inadequate flap blood flow (Fig. 2-11). The most success­
ful has been flap delay.
Research Methods
A large amount of literature is available on skin flap
physiology. Several studies give conflicting results.
Experimental results are often difficult to interpret
because of variation in choice of animal model, timing of
treatment, route of drug administration, method of data
collection, and repeatability of the study.37 Some stan­
dardization of flap research methods would help resolve
some of these difficulties.
Two basic experimental designs have been used to
investigate the consequences of a vascular insult on a
surgical flap. In one design, the blood supply to a flap is
interrupted for varying amounts of time by occluding or
otherwise interrupting flow through the vascular pedicle.
The maximum amount of ischemic time the flap can
survive in the experimental and control groups is deter­
mined. This design is used to investigate the no-reflow
phenomenon and ischemia tolerance. The second design
involves flaps with a random extension in which the effect
of an experimental manipulation on flap survival or flap
blood flow is compared with a control. From this basic
framework, a number of animal models and methods to
assess blood flow and survival have been developed in
attempts to alter skin flap viability.
determining early flap viability. Other mechanisms,
however, play an equally important role in proper flap
wound healing and determine the ultimate fate of the
flap. These additional mechanisms include the four cas­
cades (clotting, complement, kinin, plasminogen), colla­
gen formation, and collagen degradation. Optimal flap
wound healing comprises a well-orchestrated interplay of
all of these processes.
During the last decade, the role of peptide growth
factors in soft tissue wound healing has been gaining
more attention. These signal proteins contribute to flap
wound healing by controlling the recruitment and pro­
liferation of cells (endothelial, epithelial, fibroblast) that
modulate the formation of new vessels, collagen, epithe­
lium, and matrix (Fig. 2-10).
FIGURE 2-10  ■  Role of peptide growth factors. FGF, fibroblast
growth factor; IL, interleukin; PDGF, platelet-derived growth
factor; TGF, transforming growth factor.
Source
Target
cell
Repair
process
Products
released
Epithelial cell
Endothelial cell
Fibroblast
Epithelialization
Angiogenesis
Collagen and
matrix formation
Wound healing
Injured cells
Platelets
Macrophages
Lymphocytes
PDGF
TGF-β
TGF-α
PDGF
TGF-β
FGF
FGF
TGF-β
PDGF
TGF-α
IL-1
TGF-β
IL-2
INJURY
FIGURE 2-9  ■  Possible mechanism for formation of oxygen free radicals during reperfusion after ischemia and subsequent reduction
of superoxide radical.
Ischemia
ATP
AMP
Reperfusion
Hypoxanthine
Xanthine
oxidase
Allopurinol
Xanthine
oxidase
Xanthine
Uric acid
2
O
O
O
superoxide
dismutase
O
2
2
2
2
metal
catalysts
(Fe, Cu, Zn, etc.)
O2
H2
catalase, peroxidase
O2
OH

2  SKIN FLAP PHYSIOLOGY
23
by the same degree of vasoconstriction, resulting in
improved blood flow and increased survival.41
Another mechanism to increase blood flow to the
distal portion of the single pedicle flap is development of
vascular collaterals and reorientation of the major vascu­
lar channels.42 Longitudinal flow is also enhanced by
vasodilating substances released by inflammation and
mild ischemia.43 Pang et al43 thought that the depletion
of vasoconstricting substances played a role in the early
stage of delay, whereas locally released vasodilating sub­
stances were involved in the later stages (Table 2-1).
When a flap is delayed, dilation of existing vessels
within the flap occurs. The ingrowth of new vessels is not
an important mechanism. The maximal anatomic effect
on the arterial vessel appears to occur at the level of
“choke” vessels during the delay phenomenon. It is
believed that the choke vessel dilation during the delay
period is a permanent and irreversible event. Specifically,
it is an active process associated with both an increase
(hyperplasia) and an enlargement (hypertrophy) of the
cells in the choke artery wall that increases the caliber of
these vessels.44
Skin Flap Delay
Four concepts are accepted concerning the delay phe­
nomenon. First, it requires surgical trauma. Second, a
large percentage of the neurovascular supply to the flap
must be eliminated. Third, delay results in increased flap
survival at the time of tissue transfer. Fourth, the benefi­
cial effects can last up to 6 weeks in the human.38 To
explain this phenomenon, three theories regarding the
mechanism of delay have been developed: (1) delay
improves blood flow, (2) delay conditions tissue to isch­
emia,39 and (3) delay closes arteriovenous shunts.40 Most
recent papers support a mechanism resulting in increased
circulation to the flap.
Sympathetic denervation causing depletion of norepi­
nephrine within the flap is one mechanism thought to
play a role in increasing blood flow to a delayed flap.
Degeneration release of norepinephrine occurs soon
after flap elevation, and norepinephrine stores are largely
depleted in the first 24 to 48 hours.25 After catecholamine
depletion, a relative state of sympathectomy develops, but
the vasculature to the flap has an increased sensitivity to
the effects of adrenergic drugs (a hyperadrenergic state).22
Pang et al24 theorized that a change in the vasoactivity of
the small arteries allowed delivery of more blood to the
distal portion of the flap. During elevation of the biped­
icled flap, there is a release of vasoconstrictive substances
(norepinephrine, thromboxane, and serotonin). Necrosis
is not seen during the first stage of delay because the
bipedicled flap has an ample blood supply. During the
period of delay, catecholamine depletion occurs and there
is a recovery from the hyperadrenergic state. Conversion
of the delayed flap to a single pedicle is not accompanied
FIGURE 2-11  ■  Experimental attempts to affect flap survival. SOD, superoxide dismutase.
Delay phenomenon
Tissue
expansion
Alter rheology
Pentoxifylline
Direct vasodilation
histamine, isoxsuprine
Ca channel blockers, etc.
Neovascularization
Growth factors
Metabolic
manipulation
Requirements
Reserves
Increased oxygenation
Hyperbaric oxygen
Free radicals
Allopurinol, SOD,
other scavengers
Inflammation
Prostaglandins
Indirect vasodilation
-Adrenergic blockade
Norepinephrine depletion
INCREASE BLOOD SUPPLY
PROLONG TISSUE VIABILITY
2+
α
TABLE 2-1  Mechanisms of Improving Blood
Flow by the Delay Phenomenon
Depletion of vasoconstricting substances
Formation of vascular collaterals and reorientation of
vascular channels
Stimulation of an inflammatory response
Release of vasodilating substances

24
SECTION I  FUNDAMENTALS
reproducibly increase flap survival indicates that mecha­
nisms other than direct arterial dilation are important in
survival of the ischemic flap.
Neovascularization
Neovascularization can be potentially accelerated with
angiogenic growth factors to improve flap viability.
Increased flap survival and vascularity were seen when an
endothelial cell growth factor was applied in a sustained-
release fashion to accelerate peripheral neovasculariza­
tion in compromised flaps.52,53
Flap Prefabrication
Prefabrication of flaps into desired skin paddle dimen­
sions before flap transposition has recently gained more
attention. Use of angiogenic agents such as bFGF, VEGF,
and hyperbaric oxygen to increase vascularity of the skin
over the pedicle to enable a larger flap has shown promise.
With this concept, it would be possible to tailor the size
of a skin paddle of a flap by priming it with angiogenic
agents.54-57 One study showed that a prefabricated skin
flap can be created 8 weeks after arteriovenous pedicle
implantation underneath the planned tailored skin in a
rodent model.58
Alteration of Rheology
In a homogeneous fluid that exhibits equal shear stress at
different rates of shear, flow (Q) in a vessel can be approx­
imated by the Poiseuille equation:
Q
Pr
l
= ∆
4
8
π
η
where ΔP equals pressure gradient, r4 is the fourth
power of the vessel radius, l is vessel length, and η is
viscosity.4 Although blood is a non-newtonian fluid, the
qualitative relationships in the equation remain. In larger
vessels, the radius is a dominant factor; but in the capil­
lary microcirculation, viscosity becomes more important.
By decreasing the viscosity of blood, it may be possible
to increase flow to the distal random portion of the
acutely raised flap and beneficially affect flap survival.
Viscosity is influenced by the hematocrit, serum proteins,
temperature, red blood cell deformability, and aggrega­
tion as well as other factors.59 Each of these factors can
be potentially manipulated with a resultant change in
viscosity.
Pentoxifylline and low-viscosity whole blood substi­
tutes (Fluosol-DA) will also lower viscosity. Pentoxifyl­
line is a hemorrheologic agent that results in increased
red blood cell deformability and decreased platelet aggre­
gability.59 When it is given 7 to 10 days before flap eleva­
tion, pentoxifylline has increased flap survival in porcine
dorsal flank flaps60 and the rat dorsal flap.59 Beneficial
effects with limited preoperative dosing of pentoxifylline,
however, have not been uniform.61 Fluosol-DA adminis­
tration has also failed to consistently increase flap
survival.62
Cytokines may be a mechanism by which surgical
delay can increase flap survival. Basic fibroblast growth
factor (bFGF) and VEGF expressions increased signifi­
cantly after delay. In the rat flap model, surgical delay
resulted in increased VEGF expression and increased
skin paddle survival. These results correlate with previous
studies showing that the preoperative injection of VEGF
increases skin paddle survival.45
Increase of Blood Supply
Indirect Vasodilators
The intense vasoconstriction associated with release of
norepinephrine after flap elevation would seem to hinder
flap survival. As discussed before, one of the benefits of
flap delay seems to be depletion of norepinephrine before
creation of the flap to be transferred. If this vasoconstric­
tion could be blocked or reversed, the duration and sever­
ity of distal flap ischemia should be lessened. The result
would be increased flap survival without the need for
delay.
Several anesthetic agents have vasoactive properties
and may influence flap survival. Because general anes­
thetics are often used during the creation of larger flaps,
any potential effects on flap survival are important. Iso­
flurane (a sympatholytic vasodilator) was found to signifi­
cantly improve flap survival compared with nitrous oxide,
which induces vasoconstriction.46
Studies have attempted to produce a “pharmacologic
delay” by suppressing the catecholamine-induced vaso­
constriction seen after flap elevation. Methods have
included administration of alpha-adrenergic blocking
agents and depletion of norepinephrine stores, but both
methods have had mixed results and resulted in systemic
toxicity.
Direct Vasodilators
Direct vasodilators such as histamine, hydralazine, and
topical dimethyl sulfoxide have shown both a beneficial
effect and no effect on skin flap survival.37 Isoxsuprine is a
phenylethylamine derivative of epinephrine having alpha-
adrenergic receptor antagonistic and beta-adrenergic
receptor agonistic properties, resulting in relaxation
of vascular smooth muscle. Isoxsuprine was found to
increase blood flow in the area of the dominant artery in
porcine myocutaneous and arterial flaps. Unfortunately,
no improvement in blood flow was seen in the distal
random portion of the flaps or in flap survival.47 The
smaller vessels in the distal random portion of a flap were
theorized to have a sensitivity to vasodilator drugs differ­
ent from that of muscular or axial arteries. Manipulation
of these distal vascular channels appears to be critical in
increasing flap survival.
Experiments investigating the effects of other direct
vasodilators either have given mixed results or have yet to
be confirmed. Studies have attempted to increase skin flap
survival with calcitonin gene–related peptide,48 calcium
channel blockers,49 topical nitroglycerin,50 and topical
dimethyl sulfoxide.51 The failure of direct vasodilators to

2  SKIN FLAP PHYSIOLOGY
25
to concern about the use of allopurinol to increase flap
survival in the clinical setting.
A number of free radical scavengers are available to
protect the tissues from destruction by free radicals.
Superoxide dismutase (SOD), an intracellular free radical
scavenger, catalyzes the conversion of superoxide to
hydrogen peroxide (H2O2) and molecular oxygen. When
it is given systemically, SOD is an effective scavenger of
the superoxide radical regardless of its source. SOD treat­
ment has resulted in improved flap survival81,82 and
increased tolerance to ischemia of rat abdominal flaps.48
Improved flap survival has also been demonstrated with a
number of other naturally occurring compounds with free
radical scavenging properties. These include deferox­
amine83; vitamin E, vitamin A, vitamin C, and glutathi­
one84; various amino acids85; and amino acid derivatives.86
The hydrogen peroxide formed by the dismutation of
superoxide is not particularly harmful. In the presence of
chelated metal complexes, however, hydrogen peroxide
can be converted into a hydroxyl radical (OH.) by the
Fenton-type or Haber-Weiss reaction. The hydroxyl
radical is much more reactive and may be responsible for
much of the damage inflicted by oxygen free radicals.32
The presence of a hematoma under a flap may decrease
flap survival by increasing the available iron that acts as
a catalyst in the formation of free radicals.87
Nitric Oxide
Nitric oxide synthesized by the enzyme nitric oxide syn­
thase has a major physiologic importance in skin flap
survival. Nitric oxide is a radical with properties that
induce vasodilation and can protect tissues from
neutrophil-mediated ischemia-reperfusion injury. By the
administration of a nitric oxide precursor, L-arginine,
myocutaneous flaps in porcine skin were protected from
ischemia-reperfusion injury with reduced flap necrosis,
neutrophil accumulation, and edema.88 It has been pro­
posed that after reperfusion injury, endothelial cell
dysfunction leads to disruption of nitric oxide synthase–
mediated nitric oxide production and in turn causes the
deleterious effects of ischemia-reperfusion injury on flap
survival and blood reflow.89 The role of nitric oxide syn­
thase in promoting skin flap angiogenesis in its early
stages after flap transposition has shown promise.90 Nitric
oxide is also believed to be an important contributor to
the phenomenon of skin flap delay.91
Increased Tolerance of Ischemia
Increased Oxygenation.  Improvement in flap survival
with hyperbaric oxygen treatment has been documented
in the rat model.92 Hyperbaric oxygen treatment, however,
increases blood oxygen-carrying capacity by at most
20%.93 A greater effect of hyperbaric oxygen treatment
may be increasing oxygen diffusion from surrounding
perfused tissue to the ischemic portion of the flap.94
Increased flap survival occurs with treatments using 21%
hyperbaric oxygen, implying that increased oxygen could
be delivered with an increase in pressure alone.95 A treat­
ment delay of 24 hours or more after elevation of rat
Inflammation and Prostaglandins
The surgical trauma associated with an acutely raised or
delayed flap results in an inflammatory response. This
response results in a local increase in blood flow that
could benefit flap survival. Improved flap survival has
been shown with different methods of creating an inflam­
matory response before flap creation.26,63 These studies
demonstrate that the inflammatory response can be a
stimulus for “delay” without sympathectomy or vascular
division.
The mechanism by which inflammation produces a
beneficial effect appears to involve the products of cyclo­
oxygenase metabolism of arachidonic acid. On the other
hand, cyclooxygenase inhibitors such as indomethacin
and ibuprofen have been shown to increase skin flap
viability.64,65 It has been proposed that the improvement
in flap survival with low-level laser energy may be related
to a decreased expression of cyclooxygenase 2.66 Gluco­
corticoids, which inhibit phospholipase A2 activity, have
also increased flap survival in some studies.67,68 Adminis­
tration of prostaglandins that cause vasodilation and
decrease platelet aggregation tends to increase survival of
experimental flaps.69,70 Blocking of TxA2 synthesis has
had mixed results.71,72
Tissue Expansion
Tissue expansion has been demonstrated to increase the
size of a transferred flap in experimental animals and
humans. Examination of expanded skin in the guinea pig
has shown an increase in the thickness73 and mitotic activ­
ity74 of the epidermal layer, indicating epidermal prolif­
eration. Blood flow in expanded tissue is greater than in
skin overlying a noninflated expander 1 hour after cre­
ation of a pedicled flap in the porcine model.75 The
increased blood flow to expanded skin compared with
delay seems to be short-lived.76 Apart from the acute
changes seen with expander manipulation, flap viability
and blood flow appear to be similar in expanded skin and
in delayed flaps.77 Irradiation to skin reduces the amount
of skin that can safely be expanded. It also reduces the
effectiveness of surgical delay and skin flap viability.78
Prolonged Viability
Protection Against Harmful Agents
A recent focus of experiments attempting to improve flap
survival has been on the formation of free radicals with
reperfusion and the return of molecular oxygen to isch­
emic tissue. This research has focused on decreasing the
production of free radicals and employing agents that
remove free radicals (free radical scavengers) from the
immediate environment.
Administration of allopurinol (a xanthine oxidase
inhibitor) preoperatively prevents the increased xanthine
oxidase activity seen with acute flap elevation.79 Improved
survival of dorsal rat flaps has been accomplished with
allopurinol when it is given at high doses,80 with lower
doses having no effect. The high doses required have led

26
SECTION I  FUNDAMENTALS
of accelerating revascularization.53 Use of bFGF has been
shown to increase random skin flap survival of irradiated
skin flaps.110 When growth factors are administered to
influence wound healing and flap survival, it is difficult
to determine the best time and mode of delivery to maxi­
mize their therapeutic effects. One major factor is that
the half-life of growth factors is short. One article
described the feasibility of using hollow-fiber catheters
to deliver VEGF to porcine random skin flaps.111 Other
modalities for growth factor delivery continue to be
investigated.
Preliminary studies using autologous platelet-rich
plasma, which contains a number of growth factors
released from platelets, have shown increased skin flap
survival.112 When platelet-rich plasma is administered by
subcutaneous injection, platelet-rich skin flaps have an
increased blood vessel density and fewer inflammatory
cells compared with platelet-poor plasma and control
flaps. Furthermore, platelet-rich plasma flaps appeared to
have an upregulation of genes involved in angiogenesis
(elevated mRNA levels of VEGF and platelet-derived
growth factor).
TISSUE ENGINEERING
Tissue engineering to improve the survival of skin flaps
remains in its infancy. In using gene therapy to improve
flap survival, various methods have employed plasmids or
viruses to transplant genes that code for and produce
growth factors in ischemic tissue.113
One study showed that liposome-mediated gene trans­
fer could result in useful biologic effects by priming the
flap before it is raised. Specifically, cDNA encoding
VEGF complexed to commercially available liposomes
was injected into rat skin 1 week before raising of a
random flap. Flap survival was enhanced 14%.114
Another study investigated the use of adenovirus-
mediated gene therapy with VEGF (Ad-VEGF) deliv­
ered into the subdermal space to treat compromised skin
flaps. Compared with the control, both local and midline
subdermal injections of Ad-VEGF showed improved
overall flap survival.115 In ischemic tissues, flap survival
was enhanced by administration of a cDNA encoding
VEGF116 as well as by incorporation of the VEGF gene
into mesenchymal stem cells.117 The use of plasmid DNA
as a carrier for platelet-derived growth factor B delivered
subcutaneously 7 days before flap elevation may also give
an effective nonsurgical approach to increase flap survival
by increasing vascularity.118
SUMMARY
The blood flow required for nutritional support of the
skin is dramatically less than what is available to carry out
its thermoregulatory function. This allows skin to survive
a compromise of its blood supply during creation of local
flaps. The surviving length of a particular flap depends
on the relationship between the intravascular perfusion
pressure and the critical closing pressure of the arterioles
in the subdermal plexus. Appropriate flap design is the
dorsal flaps results in little benefit from hyperbaric
oxygen.96 An experiment using a porcine model was less
successful in improving flap survival.97
Metabolic Manipulation.  Decreasing the metabolic
requirements and increasing the metabolic reserves of
skin are additional strategies for increasing flap survival.
These approaches are based on the idea that flap necrosis
occurs when tissue metabolic demand is greater than
what the blood supply can deliver. Decreasing tempera­
ture is an effective way to reduce metabolic activity and
to delay necrotic changes, but improvement in flap sur­
vival is not seen.98
IMPAIRED FLAPS
Smoking tobacco is associated with an increased chance
of flap necrosis in facelift operations.99 Exposure to
tobacco smoke resulted in increased flap necrosis of
dorsal flaps in rodents.100 The deleterious effects of nico­
tine appear to increase with prolonged exposure.101 The
mechanism whereby tobacco or nicotine lowers flap sur­
vival is believed to be direct endothelial damage or vaso­
constriction secondary to catecholamine release or local
concentrations of prostaglandins. Smoking impairs flap
healing by causing vasoconstriction from nicotine and
increased levels of carboxyhemoglobin, which limits
oxygen delivery. In addition, smoking decreases neutro­
philic function and decreases collagen synthesis.102
Smoking cessation for at least 4 to 6 weeks is recom­
mended before skin flap surgery. Medications such as
varenicline (Chantix) and the electronic cigarette
(E-cigarette) may assist in cessation.
Some animal studies show that hyperbaric oxygen
can improve skin flap survival.103 Hyperbaric oxygen
therapy delivers oxygen concentrations at pressures
higher than atmospheric pressures. With a “dive” of 2.4
ATA, tissue wound partial pressure of oxygen will be 800
to 1100 mm Hg. This exposure induces vasoconstriction
with increased partial pressures of oxygen in the blood,
which subsequently stimulates angiogenesis and fibro­
blast proliferation.104 Patient side effects may include
barotrauma and exacerbation of congestive heart failure.
More clinical studies are required.
VEGF and nitric oxide cause vasodilation, increase
angiogenesis, and improve flap survival. One study
showed that a single intra-arterial dose of VEGF or
L-arginine, a substrate for nitric oxide production,
reduced flap regional necrosis.105
Irradiation has been shown to be deleterious to flap
survival in some studies.106,107 Discrepancies in these
studies are probably due to differences in the radiation
regimen administered (i.e., radiation dosage, fraction­
ation, and surgical timing in respect to the irradiation).
Radiation treatment results in endarteritis obliterans and
altered wound healing. In spite of prior irradiation, the
delay phenomenon does improve flap survival.108 Flap
neovascularization is delayed but not eliminated after
irradiation.109
The use of angiogenic growth factors has the potential
to increase the viability of irradiated skin flaps by means

2  SKIN FLAP PHYSIOLOGY
27
20. D’Amore P. The role of growth factors and cell-cell communica­
tion in the control of angiogenesis. Princton, NJ: Excerpta
Medica; 1987.
21. Su CT, Im MJ, Hoopes JE. Tissue glucose and lactate following
vascular occlusion in island skin flaps. Plast Reconstr Surg 1982;
70:202.
22. Pearl R. A unifying theory of the delay phenomenon: recovery
from the hyperadrenergic state. Ann Plast Surg 1981;7:102.
23. Mounsey RA, Brown DH, O’Dwyer TP, et al. Role of hyperbaric
oxygen therapy in the management of mandibular osteoradione­
crosis. Laryngoscope 1993;103:605.
24. Pang C, Neligan PC, Forrest C, et al. Hemodynamics and vascu­
lar sensitivity to circulating norepinephrine in normal skin and
delayed and acute random skin flaps in the pig. Plast Reconstr
Surg 1986;78:75.
25. Jurell G. Adrenergic nerves and the delay phenomenon. Ann Plast
Surg 1986;17:497.
26. Liston S. Nonbacterial inflammation as a means of enhancing skin
flap survival. Laryngoscope 1984;94:1075.
27. Macht S, Frazier WH. The role of endogenous bacterial flora in
skin flap survival. Plast Reconstr Surg 1980;65:50.
28. Kaley G, Hintze TH, Panzenbeck M, et al. Role of prostaglandins
in microcirculatory function. New York: Raven Press; 1985.
29. Nakano J. General pharmacology of prostaglandins. Philadelphia:
JB Lippincott; 1973.
30. Campbell W. Lipid-derived autacoids: eicosanoids and platelet-
activating factor. New York: Pergamon Press; 1990.
31. Murphy R, Lawrence WT, Robson M, et al. Surgical delay and
arachidonic acid metabolites: evidence for an inflammatory mech­
anism: an experimental study in rats. Br J Plast Surg 1985;38:272.
32. Southorn P, Powis G. Free radicals in medicine. I. Chemical
nature and biologic reactions. Mayo Clin Proc 1988;63:381.
33. McCord J. Oxygen-derived free radicals in postischemic tissue
injury. N Engl J Med 1985;312:159.
34. McCord J. Improved survival of island flaps after prolonged isch­
emia by perfusion with superoxide dismutase. Plast Reconstr Surg
1986;77:643.
35. Pang Y, Lineaweaver WC, Lei MP, et al. Evaluation of the mecha­
nism of vascular endothelial growth factor improvement of isch­
emic flap survival in rats. Plast Reconstr Surg 2003;112:556.
36. Kerrigan C. Skin flap failure: pathophysiology. Plast Reconstr
Surg 1983;72:766.
37. Kerrigan C, Daniel RK. Pharmacologic treatment of the failing
skin flap. Plast Reconstr Surg 1982;70:541.
38. Pearl R. The delay phenomenon: why the fuss? Ann Plast Surg
1984;13:307.
39. McFarlane RM, Heagy FC, Radin S, et al. A study of the delay
phenomenon in experimental pedicle flaps. Plast Reconstr Surg
1965;35:245.
40. Reinisch J. The pathophysiology of skin flap circulation: the delay
phenomenon. Plast Reconstr Surg 1974;54:585.
41. Pang C, Forrest CR, Neligan P, et al. Augmentation of blood flow
in delayed random skin flaps in the pig: effect of length of delay
period and angiogenesis. Plast Reconstr Surg 1986;78:68.
42. Suzuki S, Isshiki N, Ohtsuka M, et al. Experimental study on
“delay” phenomenon in relation to flap width and ischaemia. Br
J Plast Surg 1988;41:389.
43. Pang C, Neligan PC, Nakatsuka T, et al. Pharmacologic manipu­
lation of the microcirculation in cutaneous and myocutaneous
flaps in pigs. Clin Plast Surg 1985;12:273.
44. Dhar SC, Taylor GI. The delay phenomenon: the story unfolds.
Plast Reconstr Surg 1999;104:2079.
45. Lineaweaver WC, Lei MP, Mustain W, et al. Vascular endothe­
lium growth factor, surgical delay, and skin flap survival. Ann Surg
2004;239:866–73; discussion 873-5.
46. Dohar JGG, Azarshin K. The effects of inhalation anesthetic
agents on survival in a pig random skin flap model. Arch Otolar­
yngol 1992;118:37.
47. Neligan P, Pang CY, Nakatsuka T, et al. Pharmacologic action of
isoxsuprine in cutaneous and myocutaneous flaps. Plast Reconstr
Surg 1985;75:363.
48. Knight K, Martin TJ, Coe S, et al. Effect of the vasodilator pep­
tides calcitonin gene-related peptide and atriopeptin on rabbit
microvascular blood flow: preliminary communication. Br J Plast
Surg 1988;41:147.
most critical factor in maintaining adequate intravascular
perfusion pressure and avoiding tissue necrosis.
During the first 48 hours after a flap is raised, the
transferred tissue must survive a number of hazards. The
arteriolar closing pressure is increased by catecholamine
released from divided sympathetic nerves within the
tissue. An inflammatory response begins the process of
wound healing but may also impair blood flow with the
formation of tissue edema. The increased oxygen supply
available with reperfusion results in the formation of free
radicals, which can further damage tissue. Beyond the
first few days, neovascularization and wound healing
lessen the surviving flap’s dependence on the pedicle.
Attempts to improve flap survival have involved
improving flap design, altering the early physiologic
impairment of blood flow, and increasing tissue resistance
to ischemia. Surgical delay is the most effective interven­
tion. Pharmacologic manipulations designed to improve
blood flow or to increase tissue tolerance of ischemia
have not achieved the significant and reproducible results
required for incorporation into common clinical usage.
Research with growth factors and tissue engineering will
expand the horizons in tailoring flap reconstruction.
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28
SECTION I  FUNDAMENTALS
76. Ricciardeli E, Goding GS, Bright D, et al. Acute blood flow
changes in rapidly expanded and adjacent skin. Arch Otolaryngol
1989;115:182.
77. Sasaki G, Pang CY. Pathophysiology of skin flaps raised on
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79. Im M, Shen WH, Pak C, et al. Effect of allopurinol on the
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80. Pokorny A, Bright DA, Cummings C. The effects of allopurinol
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81. Zimmerman T, Sasaki GH, Khattab S. Improved ischemic island
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82. Freeman TJ, Maisel RH, Goding GS, et al. Inhibition of
endogenous superoxide dismutase with diethyldithiocarbamate
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103:938.
83. Angel M, Narayanan K, Swartz W, et al. Deferoxamine increases
skin flap survival: additional evidence of free radical involvement
in ischaemic flap surgery. Br J Plast Surg 1986;39:469.
84. Hayden R, Paniello RC, Yeung C, et al. The effect of glutathione
and vitamins A, C, and E on acute skin flap survival. Laryngoscope
1987;97:1176.
85. Paniello R, Hayden RE, Bello S. Improved survival of acute skin
flaps with amino acids as free radical scavengers. Arch Otolaryngol
1988;114:1400.
86. Kim YS, Im MJ, Hoopes JE. The effect of a free-radical scavenger,
N-2-mercaptopropionylglycine, on the survival of skin flaps. Ann
Plast Surg 1990;25:18.
87. Angel M, Narayanan K, Swartz W, et al. The etiologic role of free
radicals in hematoma-induced flap necrosis. Plast Reconstr Surg
1986;77:795.
88. Cordeiro PG, Santamaria E, Hu QY. Use of a nitric oxide precur­
sor to protect pig myocutaneous flaps from ischemia-reperfusion
injury. Plast Reconstr Surg 1998;102:2040–8; discussion 2049-51.
89. Khiabani KT, Kerrigan CL. Presence and activity of nitric oxide
synthase isoforms in ischemia-reperfusion–injured flaps. Plast
Reconstr Surg 2002;109:1638.
90. Furuta S, Vadiveloo P, Romeo-Meeuw R, et al. Early inducible
nitric oxide synthase 2 (NOS 2) activity enhances ischaemic skin
flap survival. Angiogenesis 2004;7:33.
91. McDonald WS, Lo TP Jr, Thurmond M, et al. Role of nitric oxide
in skin flap delay. Plast Reconstr Surg 2004;113:927.
92. Perrins D. The effect of hyperbaric oxygen on ischemic skin flaps.
Boston: Little, Brown; 1975.
93. Kernahan D, Zingg W, Kay C. The effects of hyperbaric oxygen
on the survival of experimental skin flaps. Plast Reconstr Surg
1965;36:19.
94. Cutting C. Skin flap physiology. St. Louis: Mosby–Year Book;
1986.
95. Tan C, Im MJ, Myers R, et al. Effect of hyperbaric oxygen and
hyperbaric air on survival of island skin flaps. Plast Reconstr Surg
1984;73:27.
96. Nemiroff P, Merwin GE, Brant T, et al. Effects of hyperbaric
oxygen and irradiation on experimental skin flaps in rats. Otolar­
yngol Head Neck Surg 1985;93:485.
97. Caffee HH, Gallagher TJ. Experiments on the effects of hyper­
baric oxygen on flap survival in the pig. Plast Reconstr Surg
1988;81:954.
98. Goding G, Cummings C, Bright D. Effects of local hypothermia
on the porcine myocutaneous flap. Philadelphia: BD Decker;
1991.
99. Rees T, Liverett DM, Guy C. The effect of cigarette smoking on
skin flap survival in the face lift patient. Plast Reconstr Surg
1984;73:911.
100. Craig S, Rees TD. The effects of smoking on experimental skin
flaps in hamsters. Plast Reconstr Surg 1985;75:842.
101. Forrest C, Pang CY, Lindsay W. Dose and time effects of
nicotine treatment on the capillary blood flow and viability of
random pattern skin flaps in the rat. Br J Plast Surg 1987;40:
295.
49. Hira M, Tajima S, Sano S. Increased survival length of experimen­
tal flap by calcium antagonist nifedipine. Ann Plast Surg 1990;
24:45.
50. Nichter L, Sobieski MW, Edgerton M. Efficacy of topical nitro­
glycerin for random-pattern skin-flap salvage. Plast Reconstr Surg
1985;75:847.
51. Myers M, Donovan W. Augmentation of tissue oxygen by
dimethyl sulfoxide and hydrogen peroxide. In: Bruley C, Dicher
H, editors. Oxygen transport to tissue: instrumentation, methods
and psychology. New York: Plenum Press; 1973.
52. Hom D, Assefa G. The effects of endothelial cell growth factor
on vascular compromised skin flaps. Arch Otolaryngol 1992;118:
624.
53. Hom D, Assefa G, Song CW. Endothelial cell growth factor
(ECGF) application to irradiated soft tissue. Laryngoscope
1993;103:165.
54. Bayati S, Russell RC, Roth AC. Stimulation of angiogenesis to
improve the viability of prefabricated flaps. Plast Reconstr Surg
1998;101:1290.
55. Haws MJ, Erdman D, Bayati S, et al. Basic fibroblast growth
factor induced angiogenesis and prefabricated flap survival. J
Reconstr Microsurg 2001;17:39–42; discussion 43-4.
56. Hickey MJ, Wilson Y, Hurley JV, et al. Mode of vascularization
of control and basic fibroblast growth factor–stimulated prefabri­
cated skin flaps. Plast Reconstr Surg 1998;101:1296–304; discus­
sion 1305-6.
57. Li QF, Reis ED, Zhang WX, et al. Accelerated flap prefabrication
with vascular endothelial growth factor. J Reconstr Microsurg
2000;16:45.
58. Kostakoglu N, Manek S, Green CJ. The development of neovas­
cularisation in flap prefabrication with vascular implantation: an
experimental study. Br J Plast Surg 1997;50:428.
59. Roth A, Briggs PC, Jones E, et al. Augmentation of skin flap
survival by parenteral pentoxifylline. Br J Plast Surg 1988;41:525.
60. Yessenow R, Maves MD. The effects of pentoxifylline on random
skin flap survival. Arch Otolaryngol Head Neck Surg 1989;115:179.
61. Chu B, Deshmukh N. The lack of effect of pentoxifylline on
random skin flap survival. Plast Reconstr Surg 1989;83:315.
62. Chowdary R, Berkower AS, Moss M, et al. Fluorocarbon enhance­
ment of skin flap survival in rats. Plast Reconstr Surg 1987;79:98.
63. Kami T, Yoshimura Y, Nakajima T, et al. Effects of low-power
diode lasers on flap survival. Ann Plast Surg 1985;14:278.
64. Sasaki G, Pang CY. Experimental evidence for involvement of
prostaglandins in viability of acute skin flaps: effects on viability
and mode of action. Plast Reconstr Surg 1981;67:335.
65. Robson M, Del Beccaro EJ, Heggers J. The effects of prostaglan­
dins on the dermal microcirculation after burning and the inhibi­
tion of the effect by specific pharmacological agents. Plast
Reconstr Surg 1979;63:781.
66. Junior I, Masson I, Oshima C, et al. Low-level laser irradiation,
cyclooxygenase-2 (COX-2) expression and necrosis of random
skin flaps in rats. Lasers Med Sci 2012;27:655.
67. Mendelson B, Woods JE. Effect of corticosteroids on the surviv­
ing length of skin flaps in pigs. Br J Plast Surg 1978;31:293.
68. Mes L. Improving flap survival by sustained cell metabolism
within ischemic cells: a study using rabbits. Plast Reconstr Surg
1980;65:56.
69. Suzuki S, Isshiki N, Ogawa Y, et al. Effect of intravenous prosta­
glandin E1 on experimental flaps. Ann Plast Surg 1987;19:49.
70. Silverman DB, Brousseau DA, Norton KJ, et al. The effect of a
topical PGE2 analogue on global flap ischemia in rats. Plast
Reconstr Surg 1989;84:794.
71. Ono I, Ohura T, Murazumi M, et al. A study on the effectiveness
of a thromboxane synthetase inhibitor (OKY-046) in increasing
survival length of skin flaps. Plast Reconstr Surg 1990;86:1164.
72. Kay S, Green C. The effect of a novel thromboxane synthetase
inhibitor dazmegrel (UK38485) on random pattern skin flaps in
the rat. Br J Plast Surg 1986;39:361.
73. Austad E, Pasyk KA, McClatchey K, et al. Histomorphologic
evaluation of guinea pig skin and soft tissue after controlled tissue
expansion. Plast Reconstr Surg 1982;70:704.
74. Francis A, Marks R. Skin stretching and epidermopoiesis. Br J Exp
Pathol 1977;58:35.
75. Marks M, Burney RE, Mackenzie J, et al. Enhanced capillary
blood flow in rapidly expanded random pattern flaps. J Trauma
1986;26:913.

2  SKIN FLAP PHYSIOLOGY
29
111. Anderson TA, Yu V, Hom DB, et al. Interstitial delivery of vascu­
lar endothelial growth factor to skin flaps. Arch Facial Plast Surg
2010;12:326.
112. Li W, Enomoto M, Ukegawa M, et al. Subcutaneous injections of
platelet-rich plasma into skin flaps modulate proangiogenic gene
expression and improve survival rates. Plast Reconstr Surg 2012;
129:858.
113. Waller W, Lee J, Zhang F, Lineaweaver WC. Gene therapy in
flap survival. Microsurgery 2004;24:168.
114. Liu PY, Tong W, Liu K, et al. Liposome-mediated transfer of
vascular endothelial growth factor cDNA augments survival of
random-pattern skin flaps in the rat. Wound Repair Regen 2004;
12:80.
115. Lubiatowski P, Goldman CK, Gurunluoglu R, et al. Enhancement
of epigastric skin flap survival by adenovirus-mediated VEGF
gene therapy. Plast Reconstr Surg 2002;109:1986.
116. Taub PJ, Marmur JD, Zhang WX, et al. Locally administered
vascular endothelial growth factor cDNA increases survival of
ischemic experimental skin flaps. Plast Reconstr Surg 1998;102:
2033.
117. Zheng Y, Yi C, Xia W, et al. Mesenchymal stem cells transduced
by vascular endothelial growth factor gene for ischemic random
skin flaps. Plast Reconstr Surg 2008;121:59.
118. Hijjawi J, Mogford JE, Chandler LA, et al. Platelet-derived
growth factor B, but not fibroblast growth factor 2, plasmid DNA
improves survival of ischemic myocutaneous flaps. Arch Surg
2004;139:142.
102. Sorensen LT, Karlsmark T, Gottrup F. Abstinence from smoking
reduces incisional wound infection: a randomized controlled trial.
Ann Surg 2003;238:1.
103. Friedman HI, Fitzmaurice M, Lefaivre JF, et al. An evidence-
based appraisal of the use of hyperbaric oxygen on flaps and grafts.
Plast Reconstr Surg 2006;117:175S–90S; discussion 191S-2S.
104. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J
Med 1996;334:1642.
105. Komorowska-Timek E, Timek TA, Brevetti LS, et al. The effect
of single administration of vascular endothelial growth factor or
l-arginine on necrosis and vasculature of the epigastric flap in the
rat model. Br J Plast Surg 2004;57:317.
106. Patterson T, Berry R, Hopewell J, et al. The effect of radiation in
survival of experimental skin flaps. In: Grabb WC, Myers MB,
editors. Skin flaps. Boston: Little, Brown; 1975.
107. Young CM, Hopewell JW. The effects of preoperative x-irradiation
on the survival and blood flow of pedicle skin flaps in the pig. Int
J Radiat Oncol Biol Phys 1983;9:865.
108. Fisher J, Hurn I, Rudolph R, et al. The effect of delay on
flap survival in an irradiated field. Plast Reconstr Surg 1984;73:
99.
109. Clarke H, Howard CR, Pynn B, et al. Delayed neovascularization
in free skin flap transfer to irradiated beds in rats. Plast Reconstr
Surg 1985;75:560.
110. Hom D, Unger G, Pernell K, et al. Improving surgical wound
healing with basic fibroblast growth factor after radiation. Laryn­
goscope 2005;115:412.

30
C H A P T E R 3 
BIOMECHANICS OF SKIN FLAPS
Wayne F. Larrabee Jr.  •  Cody A. Koch
INTRODUCTION
Scientific and clinical research in the areas of wound
healing and the biomechanics of skin flaps has changed
skin flap design from erratic, unsure, and artistic to con­
sistent, scientific, and artistic. Today, skin flap design
emphasizes vascular patterns, skin physiology, and the
biomechanical characteristics of cutaneous tissue. Because
the unique mechanical properties of skin influence blood
flow and flap survival, they are integral in the design of
local skin flaps. The study of soft tissue biomechanics has
increased precision and reliability of local cutaneous
flaps, ensuring the use of local flaps as the procedure of
choice for reconstruction of small and medium-sized
facial defects that cannot be closed primarily.
BIOMECHANICAL PROPERTIES OF
CUTANEOUS TISSUE
The mechanical properties of a material are described by
the relationship that exists between a force applied to a
specimen and the resultant deformation of the specimen
as a function of time. In engineering, these mechanical
properties are defined by the quantities stress (force per
unit of original cross section) and strain (change in length
divided by the original length). The stress/strain ratio
thus measures the relationship between force and elonga­
tion by said force for a given cross-sectional area. The
stress-strain relationship is independent of the dimen­
sions of the specimen and is a property of the material
itself. Uniform materials, such as titanium, have a linear
stress-strain relationship. Their mechanical properties
can be described by the proportionality constant (C =
stress/strain). If the stress-strain relationship does not
vary as a function of time, the material is said to be elastic.1
Unlike many engineering materials, skin is a hetero­
geneous substance composed of a network of dissimilar
materials. Skin is a living tissue, capable of proliferation,
change, and response to physical stimulus. It is not sur­
prising that the mechanical properties of skin are unique
compared with other materials. For simplicity, skin can
be said to have three basic mechanical properties: non­
linearity, anisotropy, and viscoelasticity.
Nonlinearity
This mechanical behavior of skin is attributable to its
heterogeneous nature. Skin is composed of a series of
interrelated networks that are intimately entwined. Struc­
turally important components in the dermis include
collagen fibers, elastic fibers, nerve fibers, capillaries,
lymphatics, and ground substance. Skin without tension
has collagen fibers distributed throughout the dermis in
a haphazard, diffuse manner. Collagen is woven in a mul­
tidirectional array without preferential orientation of
thick and thin bundles. Numerous connections between
collagen bundles form a continuous network without
visible free ends. There are no restrictive attachments
among adjacent collagen bundles that seem free to glide,
relative to each other. Elastic fibers loop spirally around
collagen and attach at multiple points along each bundle.
Elastic fibers function as a type of energy storage device,
bringing stretched collagen back to a relaxed position.
Structural proteins are found in the interstitial fluid that
acts as a lubricant enabling movement on the one hand
while acting as a buffer to resist rapid change on the
other.
A typical stress-strain curve for isolated skin is shown
in Figure 3-1. The shape of the curve is similar to stress-
strain and force-advancement curves obtained from tests
on skin flaps and other soft tissues.1 It is apparent from
the graph that skin and skin flaps have nonlinear stress-
strain relationships. The mechanical behavior can be
divided into three separate regions: (1) an initial flat
section in which considerable extension occurs with little
force, (2) an intermediate section of rapid transition, and
(3) a terminal section where little extension is possible
despite great increases in applied force. Histologic exami­
nations of the sequential stages of skin extension provide
an explanation for the nonlinear nature of this graph.
During initial deformation, randomly oriented collagen
and elastic fibers are stretched in the direction of the
applied force. Collagen fibers do not bear a significant
burden until the bundle is completely straight in the
direction of the applied force.1 As a result, there is little
resistance to initial deformation, and the stress-strain
relationship is nearly linear and elastic (region 1). As
deformation progresses, additional collagen fibers are
recruited into the load-carrying role and resistance rises.
The low stress required for the high strain inherent in
region 1 allows the small movements resulting from
flexion and extension at joints, enabling freedom of
movement and natural facial expression. Region 2 is the
strain at which many collagen fibers transition from non–
load carrying to a load-carrying role. At high-stress loads
(region 3), virtually all the dermal collagen fibers are
aligned in the direction of the applied force. At this point,

3  BIOMECHANICS OF SKIN FLAPS
31
incision made at a right angle to the RSTL will gape
widely and is more likely to produce a widened or hyper­
trophic scar. The lines of maximal extensibility (LME)
run perpendicular to the RSTLs and represent the direc­
tion in which closure can be performed with the least
tension.5 Therefore, elliptical excisions should be per­
formed parallel to the RSTLs to place the maximum
closure tension parallel to the LME and local skin flaps
should be designed so that the donor site closure is paral­
lel to the LME.
RSTLs are not to be confused with Langer’s lines.
Langer’s lines of cutaneous tension correspond to the
orientation of forces that cause a circular puncture mark
in the skin of a cadaver to distort into a fusiform shape.
The orientation of Langer’s lines is often distinct from
the creases formed in living subjects when the joints are
placed in a relaxed position. RSTLs follow the longest
and straightest furrows formed when skin is relaxed and
are not visible features of the skin. Rather, RSTLs derive
from the act of pinching the skin and observing the
furrows and ridges that form.3 When skin tension is pre­
served at the time of biopsy, a small number of extracel­
lular collagen and elastin bundles have been demonstrated
to run parallel to the RSTLs.4
Viscoelasticity
When a material resists shear flow and strain in a linear
fashion related to time in response to a force, it is said to
no further deformation is possible because of the inex­
tensible nature of fully oriented collagen. Wholly ori­
ented collagen (region 3) preserves the structural integrity
of skin by limiting deformation during accidental stresses.1
Raposio and Nordstrom2 studied the stress-strain curve
of human scalp tissue during serial excision of the scalp
and found scalp to be initially linear from 0 to 500 g,
gradually reduced in compliance from 500 to 1500 g, and
rapidly increasing in stiffness from 1500 to 5000 g.
Anisotropy
There are enormous individual variations in the extensi­
bility of human skin—differences between the slim and
obese, young and old, male and female. The shape of the
force-advancement curve is further influenced by edema,
inflammation, hormonal conditions, and body weight. It
is the variation in skin tension within the same individual,
however, that is the most interesting to the reconstructive
surgeon. On the face, the skin is lax around the eyes and
cheek, whereas it is taut on the nose, chin, and forehead.
In each of these locations, there are directional (anisotro­
pic) considerations for skin movement. In most regions
of the body, there is skin tension in every direction, but
the degree of tension is greatest parallel to the relaxed
skin tension lines (RSTLs).3 Pierard and Lapiere4 showed
that the presence of skin tension lines depends on the
interaction between elastic fibers and collagen fibers
and the anchorage of collagen fibers to each other. An
FIGURE 3-1  ■  Stress-strain curve for isolated skin
can be divided into three separate regions. Aged
skin deforms under its own weight, shifting
apparent origin of curve along x-axis. (From
Larrabee WF Jr: Immediate repair of facial defects.
Dermatol Clin 7:662, 1989.)
Strain (length)
Aged skin
Young skin
1
2
3
Stress (force)

32
SECTION I  FUNDAMENTALS
indirectly, in which the force is sensed by other cells, such
as sensory nerves, leading to the release of chemical
mediators that act on nearby cells.
Direct Mechanotransduction
Direct mechanotransduction is the process by which a
cell converts mechanical stimuli into biochemical signals.
For a cell to convert a mechanical signal to a biochemical
signal, it must be able to sense the signal. Ingber8 pro­
posed the idea of “tensegrity,” in which a cell’s cytoskel­
etal framework is coupled to the extracellular matrix as
well as to the cytoskeletal framework of nearby cells,
creating a homeostasis of tension from which deviations
might be recognized.
Cellular adhesion molecules, such as integrins, are key
to tensegrity. Integrins couple the extracellular matrix to
the actin cytoskeleton. This coupling allows integrins to
transduce changes from external mechanical forces into
the cell and vice versa. The activation of integrins, which
are primarily in an off state in the cellular membrane,
can modulate downstream signaling events controlling a
wide variety of cellular events including apoptosis, pro­
liferation, and gene expression, among others.9 Altered
expression of integrins has been implicated in studies
of wound healing and chronic wounds. For example,
Hakkinen et al10 used in situ hybridization to investigate
the expression of β6 integrin in chronic wounds, hyper­
trophic scars, and keloids in humans. The authors found
that chronic wounds expressed high levels of β6 integrin,
whereas keloids and hypertrophic scars did not demon­
strate any expression. Furthermore, the authors engi­
neered a homozygous transgenic mouse line that
constitutively expressed β6 integrin in skin epithelium
and found that a significant percentage (27%) of these
mice spontaneously developed chronic wounds, suggest­
ing that altered expression of integrins might be respon­
sible in some cases of poor healing.
Whereas the mechanisms of mechanotransduction by
integrins have been the best characterized, cells possess
other means by which to translate mechanical forces into
biochemical signals. Some cells possess mechanosensitive
ion channels that respond to mechanical forces with
either the activation or inactivation of an ion flux.11 One
of the most important of these is the mechanosensitive
calcium ion channel. Yano et al12 cultured human kerati­
nocytes on flexible dishes that were stretched 20% and
discovered that the stretching induced hyperproliferation
as measured by BrdU incorporation secondary to the
activation of extracellular signal–regulated kinases
(ERK1/2). The possibility of a role for the mechanosensi­
tive calcium-gated ion channel was suggested by almost
complete inhibition of hyperproliferation when a calcium
channel inhibitor was cultured with the cells.
Protein deformation is another mechanism of direct
mechanotransduction.13 Protein deformation is the
process by which mechanical forces induce conforma­
tional changes to a protein, which may unmask new
binding motifs or, alternatively, mask previously accessi­
ble binding sites. For example, Tamada et al14 removed
the cell membranes and soluble proteins from human
be viscous. Elastic materials demonstrate immediate
strain when a force is applied but return to their original
state when the force is removed. Skin exhibits properties
of both viscosity and elasticity (viscoelasticity). Skin
behaves like an elastic substance only during initial defor­
mation at low stress level (see Fig. 3-1, region 1). At
higher stress loads, skin shows viscoelastic properties, and
strain becomes a function of both load and time. Two
time-dependent properties of skin that are routinely
exploited by surgeons are creep and stress relaxation.
Creep refers to the increase in the length of skin com­
pared with the original length when skin is placed under
a constant stress (force per unit area). At high-stress
loads, a modicum of creep can be achieved in a short
time. A small increase in length (strain) occurs as com­
pressed and straightened collagen fibers displace intersti­
tial fluid that is loosely bound to the extracellular matrix
(ground substance). When skin is stretched in air, it is
possible to see this fluid collect on the undersurface.6
Time is required for fluid to move from one area to
another, which explains the time dependence of the
process. This mechanism partially explains the biome­
chanical and histologic changes that occur during tissue
expansion, obesity, and pregnancy.
Stress relaxation and creep are related. Stress relax­
ation refers to a decrease in stress that occurs when skin
is held under tension at a constant strain. If a skin flap is
closed under excessive tension, a certain amount of relax­
ation occurs as the tissue creeps. Stress relaxation allows
large lesions in inelastic regions to be removed with serial
excision. It also accounts for the improved vascularity
observed in the first 24 hours of flaps closed under
tension. These biomechanical properties may save a
questionable flap but should not be an integral part of
flap design.
MECHANOTRANSDUCTION AND SKIN
The mechanical properties of skin including nonlinearity,
anisotropy, and viscoelasticity are readily observed at a
macroscopic level and exploited during reconstructive
surgery. It stands to reason that the physical forces applied
to skin at the macroscopic level would induce changes at
the cellular level. Some of the first evidence of this at a
cellular level was provided by Folkman and Moscona7 in
1978. The authors grew cells in culture in varying con­
centrations of poly(2-hydroxyethyl methacrylate) to
control cell shape and, indirectly, cell tension and found
that varying shape and tension resulted in differences in
DNA synthesis and proliferation. These results suggested
that cells sense changes in force and respond accordingly
at the molecular level. The mechanism by which these
mechanical forces lead to cellular responses came to be
called mechanotransduction.
Mechanotransduction requires that cells be able to
sense a mechanical stimulus, which in turn leads to the
activation of biochemical signaling pathways to achieve
the desired end result (i.e., apoptosis, proliferation).
Mechanotransduction can act on cells directly, in which
the cell senses and acts on the mechanical force itself, or

3  BIOMECHANICS OF SKIN FLAPS
33
SURGICAL APPLICATIONS OF THE
BIOMECHANICS OF SKIN
Tissue Expansion
Physiologic tissue expansion occurs during rapid growth
at puberty, during pregnancy, and at times of rapid weight
gain. During both pregnancy and rapid growth, the time
interval can be relatively short and skin thinning can
occur as evidenced by the striae that sometimes form.
Obesity causes an overall increase in skin surface area
to occur, but the skin maintains a normal thickness in
both the epidermis and dermis with a normal collagen
content.23
The first clinical application of tissue expansion was
published by Neumann24 in 1957 and then improved
by Radovan.25 Although it is clinically useful, debate
has centered on the biomechanical properties of the
expanded skin. Preservation of epidermal thickness
during tissue expansion has been verified by several
authors.26,27 The underlying mechanism for the overall
increase in skin surface area without thinning of the epi­
dermis is increased epidermal mitotic activity and kerati­
nocyte proliferation.28-30 The long-term effects of tissue
expansion on the dermis are more difficult to discern.
Unequivocally, dermal thickness is reduced both during
tissue expansion and for an undefined period thereafter.
What is not clear, however, is whether eventual restora­
tion of the normal dermis occurs and by what mecha­
nism. Johnson et al28,31 demonstrated in a porcine model
that an increase in surface area of skin occurred during
and after tissue expansion but that dermal thinning per­
sisted for 36 weeks after completed expansion (Fig. 3-2).
Clinical extrapolation of these data is difficult because the
tissue expanders were left in place (Fig. 3-3). Dermal
compensation in response to tissue expansion appears to
be slow compared with the rapid response found in the
epidermis. This discrepancy is found during pregnancy
but not during chronic obesity, in which both dermal
thickness and epidermal thickness are preserved.23
Expanded skin does demonstrate an increase in vascular­
ity as well as in vasodilation, thought to account for the
increased mean surviving lengths of expanded skin flaps
compared with random skin flaps.26
Gibson and Kenedi6 first suggested that additional
tissue for wound closure could be obtained by acutely
stretching the skin. The clinical efficacy of intraoperative
cyclic loading of skin was thought to derive primarily
from the effects of increased undermining.32 However,
others have shown that intraoperative tissue expansion
increases skin compliance with decreased tension com­
pared with simple undermining.33
Wound Tension and Blood Flow
The effect of wound closure tension on blood flow has
been studied by comparing tissue survival to wound
closure tensions in animal models.6,34 A quantitative
description of the relationship between blood flow
and wound closure tension is seen in Figure 3-4. In
this experimental pig model, the investigators created a
embryonic kidney cells and demonstrated that stretching
of the remaining cytoskeleton could activate the protein
Rap1, which is important for the activation of the
p38 mitogen-activated protein kinase cascade. Similarly,
transforming growth factor β1 (TGF-β1) is an important
mediator of inflammation and wound healing. TGF-β1
typically remains in an inactive state bound to latency-
associated peptide in the large latent complex. The
binding of integrins to the large latent complex can cause
conformational changes in the large latent complex and
dissociation of the latency-associated peptide from TGF-
β1, which renders it active.15
Indirect Mechanotransduction
Indirect mechanotransduction involves a cell-sensing
mechanical force leading to the release of proteins or
other chemical messengers, which then act on nearby
cells to mediate a variety of effects. One example of indi­
rect mechanotransduction is the peripheral nervous
system. The peripheral nervous system contains mecha­
nosensitive and nociceptive sensory nerves that sense
mechanical forces and effect changes on surrounding
cells. The skin contains low-threshold mechanorecep­
tors, such as Meissner’s corpuscles, as well as high-
threshold nociceptors, which sense pain as well as
mechanical forces. The activation of nociceptors leads to
the release of neuropeptides from afferent sensory nerve
endings. The neuropeptides released from afferent
sensory nerve endings include calcitonin gene–related
peptide (CGRP), substance P (SP), somatostatin, and
vasoactive intestinal peptide (VIP), among others. For
example, Chin et al16 used a murine model of skin stretch­
ing in which skin was exposed to cyclic or continuous
stretch for 4 hours and observed increased expression of
both SP and CGRP.
The neuropeptides released by sensory nerve endings
act on nearby cells, leading to vasodilation, cytokine pro­
duction, and increased vascular permeability, among
others.17 Keratinocytes possess receptors for SP, VIP, and
CGRP.18 Activation of the receptor for SP on human and
murine keratinocytes induces proliferation while pro­
moting migration of fibroblasts.19,20
The release of neuropeptides in response to mechani­
cal forces has also been implicated in inflammation and
wound healing.21 SP and CGRP serve to initiate neuro­
genic inflammation by acting on mast cells.18 Binding of
SP and CGRP to their receptors on mast cells leads to
degranulation and histamine release with subsequent ery­
thema, vasodilation, and capillary leakage. Additional
effects of SP include stimulation of the release of tumor
necrosis factor 1 from mast cells and interleukins 1 and
4 from keratinocytes and upregulation of intercellular
adhesion molecules, which lead to increased binding of
immune cells to endothelium and subsequent migration
into the tissue. SP also induces endothelial cell prolifera­
tion, leading to neovascularization and angiogenesis
important for wound healing.22 Deviations of mechano­
transduction leading to prolific inflammation have been
implicated in the development of keloids and hypertro­
phic scars.

34
SECTION I  FUNDAMENTALS
Flap Design and Undermining
Minor variations in flap design can alter the mechanical
characteristics of cutaneous tissue and change the force
necessary for advancement and wound closure. A prop­
erly designed skin flap will minimize wound closure
tension and maintain critical blood flow. In like manner,
a poorly designed flap risks injury to important nutrient
vessels while securing little or no mechanical advantage.
Many practical questions concerning proper flap design
have already been addressed in the pig model. According
to Larrabee and Sutton,36 the rectangular advancement
flap should be designed with a length-to-width ratio of
at least 1 : 1. After this point, an increase in the ratio
results in a gradual decline in wound closure tension.
Further increases in the length-to-width ratio are not
always profitable and may risk necrosis of the distal
portion of the flap. Advancement flaps should be designed
with use of the minimal length-to-width ratio necessary
to effect a low-tension closure. When facial flaps are
used, a ratio between 1 : 1 and 2 : 1 is ideal; further length­
ening is usually unnecessary. Similarly, animal models
have shown little mechanical benefit of extending rota­
tion flaps past 90°.36 Other considerations, such as skin
redraping, may warrant the use of longer rotation flaps.
random skin flap 3 cm wide and 6 cm long. Laser Doppler
blood flow measurements were taken at the base of the
flap (area 4) and at 2-cm intervals toward the distal tip
(area 1). Tension was increased by 50-g increments to
maximal tension. This experiment demonstrated that
blood flow is inversely proportional to the distance from
the base of the flap and that it decreases steadily with
increasing tension until a critical value of 200 to 250 g is
reached.35 On the basis of the supporting evidence in
Figure 3-4, it seems fair to conclude that excess wound
closure tension can result in necrosis, especially at the
distal aspect of a flap. Larrabee et al35 explored this pos­
sibility by designing a study to measure the effect of
tension on survival of 3-cm-wide flaps with a length of 0
to 9 cm (Fig. 3-5). Not surprisingly, all flaps longer than
6 cm underwent some necrosis and all flaps shorter than
1.5 cm remained viable, irrespective of wound closure
tension. Flaps of intermediate length were sensitive to the
effects of tension. Flaps closed with less than 250 g of
tension tended to survive, and those closed under greater
tension tended to have areas of necrosis.35 This study
confirms the clinical observation that flaps with ample
blood flow can withstand the extremes of tension.
However, flaps subjected to excessive wound closure
tension can necrose because of insufficient blood flow.
FIGURE 3-2  ■  Increase in surface area seen with tissue expansion. Tissue expanders were left implanted during postexpansion period.
(From Johnson PE, Kernahan DA, Bauer BS: Dermal and epidermal response to soft-tissue expansion in the pig. Plast Reconstr Surg 81:391,
1988.)
Weeks post expansion
0
6
12
18
24
30
20
30
40
36
Surface area (cm2)
Control
Sham
Expanded

3  BIOMECHANICS OF SKIN FLAPS
35
SUMMARY
With experience, a surgeon develops an intrinsic under­
standing of the biomechanical properties of skin and can
intuitively determine the degree that skin will stretch
when designing and positioning skin flaps. The nonlinear
stress-strain curve for skin determines wound closure
tension, blood flow, and flap survival. Flaps of intermedi­
ate length are most sensitive to the effects of tension.
Minor variations in skin flap design can avoid excess
tension and allow wound closure within the initial portion
of the force-deformation curve. Because skin is anisotro­
pic, directional variation in skin extensibility exists, and
incisions should be placed parallel to the RSTLs to
minimize tension on the wound. Time-dependent prop­
erties of skin, such as creep and stress relaxation, are
clinically useful phenomena that permit tissue expansion
and serial excision. The molecular processes that underlie
the gross biomechanical properties of skin continue to be
elucidated.
The forces that resist skin flap advancement are more
complex than we have discussed thus far. The edge of a
skin flap is advanced both to stretch the skin and to over­
come resistance between the dermis and underlying
tissues.37 The magnitude of this resistance (shearing force)
varies considerably, depending on the site and age of the
patient. Shearing forces can often be reduced by under­
mining in the subcutaneous plane. With undermining,
vertical attachments between the dermis and tissue
beneath the dermis are lysed, releasing the skin to slide
unrestricted over the subcutaneous tissue. As undermin­
ing is increased, the origin of the shearing force is moved
away from the edge of the flap and more free skin is avail­
able for low-resistance redraping (stretching). Most of the
benefit from undermining is achieved within the first 1 to
2 cm. Undermining beyond a short distance risks injury
to surrounding structures and may compromise blood
flow. In broad-based flaps, extensive undermining has
been shown to result in an unexplained increase in the
force necessary for advancement (Figs. 3-6 and 3-7).37,38
FIGURE 3-3  ■  Dermal thickness after tissue expansion. Persistent thinning is noted 36 weeks after expansion. Tissue expanders were
left implanted during postexpansion period. (From Johnson PE, Kernahan DA, Bauer BS: Dermal and epidermal response to soft-tissue
expansion in the pig. Plast Reconstr Surg 81:391, 1988.)
Weeks post expansion
Dermal thickness (µm)
Unexpanded
Expanded
standard error
of mean
2000
0
6
12
18
24
30
36
3000
4000
x

36
SECTION I  FUNDAMENTALS
FIGURE 3-4  ■  Relationship between tension and blood flow in 3-cm-wide and 6-cm-long random skin flap. Measurements were taken
at 2-cm intervals from base of flap (area 4) to distal tip (area 1). Flow decreases steadily until critical value of 200 to 250 g is reached.
(From Larrabee WF Jr, Holloway GA Jr, Sutton D: Wound tension and blood flow in skin flaps. Ann Otol Rhinol Laryngol 93:114, 1984.)
Flap tension (g)
Control
Flap raised
50 g
150 g
250 g
350 g
400 g
500 g
600 g
700 g
800 g
900 g
Tension released
15 min. wait
Sutured
Laser Doppler measurement
Area 1
Area 2
Area 3
Area 4
0
10
20
30
40
50
60
70
80
90
100
Laser Doppler measurement of flap
blood flow with increasing tension

3  BIOMECHANICS OF SKIN FLAPS
37
FIGURE 3-5  ■  Effect of tension on survival of random patterned skin flaps. Flaps of intermediate length are sensitive to effects of
tension. Flaps closed with less than 250 g of tension tended to survive, whereas flaps closed with greater tension underwent necrosis.
(From Larrabee WF Jr, Holloway GA Jr, Sutton D: Wound tension and blood flow in skin flaps. Ann Otol Rhinol Laryngol 93:114, 1984.)
Necrosis
No necrosis
Flap length (cm)
Closing tension (g)
0
0
200
400
600
800
1000
1200
1400
1600
2
4
6
8
10

38
SECTION I  FUNDAMENTALS
FIGURE 3-6  ■  A 2 × 6-cm fusiform defect was created and undermined 2, 4, and 6 cm. (From Larrabee WF Jr: Design of local skin flaps.
In Thomas JR, editor: American Academy of Otolaryngology HNS Instructional Courses, vol 3, St. Louis, Mosby–Year Book, 1990.)
Undermining (u)
of skin flap
6 cm
2
cm
u = 2 cm
u = 4 cm
u = 6 cm

3  BIOMECHANICS OF SKIN FLAPS
39
REFERENCES
1. Daly CH, Odland GF. Age-related changes in the mechanical prop­
erties of human skin. J Invest Dermatol 1979;73:84–7.
2. Raposio E, Nordstrom RE. Tension and flap advancement in the
human scalp. Ann Plast Surg 1997;39:20–3.
3. Borges AF. Relaxed skin tension lines. Dermatol Clin 1989;7:
169–77.
4. Pierard GE, Lapiere CM. Microanatomy of the dermis in relation
to relaxed skin tension lines and Langer’s lines. Am J Dermatopa­
thol 1987;9:219–24.
5. Borges AF. The rhombic flap. Plastic Reconstr Surg 1981;67:
458–66.
6. Gibson T, Kenedi RM. Biomechanical properties of skin. Surg Clin
North Am 1967;47:279–94.
7. Folkman J, Moscona A. Role of cell shape in growth control.
Nature 1978;273:345–9.
8. Ingber DE. Cellular mechanotransduction: putting all the pieces
together again. FASEB J 2006;20:811–27.
FIGURE 3-7  ■  Force required to advance skin flap
after undermining 2, 4, and 6 cm. Increasing
undermining from 4 to 6 cm had little effect on
force necessary for advancement. (From Larrabee
WF Jr, Sutton D: Variation of skin stress-strain curves
with undermining. Surg Forum 32:555, 1981.)
Advancement (mm)
0
0
100
200
300
400
500
600
700
800
(g)
u = 2
u = 4
u = 6
5
10
15
20
25
Stress-strain curves
with 2, 4, and 6 cm undermining (u)
9. Hynes RO. Integrins: bidirectional, allosteric signaling machines.
Cell 2002;110:673–87.
10. Hakkinen L, Koivisto L, Gardner H, et al. Increased expression of
β6-integrin in skin leads to spontaneous development of chronic
wounds. Am J Pathol 2004;164:229–42.
11. Sachs F, Morris CE. Mechanosensitive ion channels in nonspecial­
ized cells. Rev Physiol Biochem Pharmacol 1998;132:1–77.
12. Yano S, Komine M, Fujimoto M, et al. Mechanical stretching in
vitro regulates signal transduction pathways and cellular prolifera­
tion in human epidermal keratinocytes. J Invest Dermatol 2004;
122:783–90.
13. Reichelt J. Mechanotransduction of keratinocytes in culture and in
the epidermis. Eur J Cell Biol 2007;86:807–16.
14. Tamada M, Sheetz MP, Sawada Y. Activation of a signaling cascade
by cytoskeleton stretch. Dev Cell 2004;7:709–18.
15. Wipff PJ, Hinz B. Myofibroblasts work best under stress. J Bodyw
Mov Ther 2009;13:121–7.
16. Chin MS, Lancerotto L, Helm DL, et al. Analysis of neuropeptides
in stretched skin. Plast Reconstr Surg 2009;124:102–13.

40
SECTION I  FUNDAMENTALS
17. Ogawa R. Mechanobiology of scarring. Wound Repair Regen
2011;19(Suppl 1):s2–9.
18. Peters EM, Ericson ME, Hosoi J, et al. Neuropeptide control
mechanisms in cutaneous biology: physiological and clinical signifi­
cance. Journal Invest Dermatol 2006;126:1937–47.
19. Scholzen T, Armstrong CA, Bunnett NW, et al. Neuropeptides in
the skin: interactions between the neuroendocrine and the skin
immune systems. Exp Dermatol 1998;7:81–96.
20. Kahler CM, Sitte BA, Reinisch N, et al. Stimulation of the chemo­
tactic migration of human fibroblasts by substance P. Eur J Phar­
macol 1993;249:281–6.
21. Akaishi S, Ogawa R, Hyakusoku H. Keloid and hypertrophic scar:
neurogenic inflammation hypotheses. Med Hypotheses 2008;71:
32–8.
22. Steinhoff M, Stander S, Seeliger S, et al. Modern aspects of cutane­
ous neurogenic inflammation. Arch Dermatol 2003;139:1479–88.
23. Black MM, Bottoms E, Shuster S. Skin collagen and thickness in
simple obesity. Br Med J 1971;4:149–50.
24. Neumann CG. The expansion of an area of skin by progressive
distention of a subcutaneous balloon; use of the method for secur­
ing skin for subtotal reconstruction of the ear. Plast Reconstr Surg
(1946) 1957;19:124–30.
25. Radovan C. Breast reconstruction after mastectomy using the tem­
porary expander. Plast Reconstr Surg 1982;69:195–208.
26. Cherry GW, Austad E, Pasyk K, et al. Increased survival and vas­
cularity of random-pattern skin flaps elevated in controlled,
expanded skin. Plast Reconstr Surg 1983;72:680–7.
27. Austad ED, Pasyk KA, McClatchey KD, et al. Histomorphologic
evaluation of guinea pig skin and soft tissue after controlled tissue
expansion. Plast Reconstr Surg 1982;70:704–10.
28. Johnson PE, Kernahan DA, Bauer BS. Dermal and epidermal
response to soft-tissue expansion in the pig. Plast Reconstr Surg
1988;81:390–7.
29. Olenius M, Dalsgaard CJ, Wickman M. Mitotic activity in expanded
human skin. Plast Reconstr Surg 1993;91:213–6.
30. Austad ED, Thomas SB, Pasyk K. Tissue expansion: dividend or
loan? Plast Reconstr Surg 1986;78:63–7.
31. Johnson PE, Kernahan DA, Bauer BS. Dermal and epidermal
response to soft-tissue expansion in the pig. Plast Reconstr Surg
1988;81:390–7.
32. Mackay DR, Saggers GC, Kotwal N, et al. Stretching skin: under­
mining is more important than intraoperative expansion. Plast
Reconstr Surg 1990;86:722–30.
33. Raposio E, Cella A, Panarese P, et al. Quantitative benefits pro­
vided by acute tissue expansion: a biomechanical study in human
cadavers. Br J Plast Surg 2000;53:220–4.
34. Stell PM. The effects of varying degrees of tension on the viability
of skin flaps in pigs. Br J Plast Surg 1980;33:371–6.
35. Larrabee WF Jr, Holloway GA Jr, Sutton D. Wound tension
and blood flow in skin flaps. Ann Otol Rhinol Laryngol 1984;93
(Pt 1):112–5.
36. Larrabee WF Jr, Sutton D. The biomechanics of advancement and
rotation flaps. Laryngoscope 1981;91:726–34.
37. Cox KW, Larrabee W Jr. A study of skin flap advancement as a
function of undermining. Arch Otolaryngol 1982;108:151–5.
38. Larrabee WF Jr, Trachy R, Sutton D, et al. Rhomboid flap dynam­
ics. Arch Otolaryngol 1981;107:755–7.

41
C H A P T E R 4 
WOUND CLOSURE TECHNIQUES
Benjamin C. Marcus  •  Jonathan M. Sykes
INTRODUCTION
Local flap procedures can offer patients excellent options
for the repair of soft tissue defects. After proper design
and execution, the long-term results can be very satisfac­
tory. Regardless of the local flap selected, proper soft
tissue techniques are vital to the success of the procedure.
A well-designed local flap may be compromised if wound
closure is poorly performed. In contrast, even lengthy
suture lines can result in favorable scars with implemen­
tation of judicious skin undermining and proper eversion
of wound edges. In addition, use of newer dissolvable
sutures and fibrin-based tissue sealants has broadened the
options for repair of skin incisions.
WOUND HEALING
Proper wound closure techniques aid the body’s natural
process of wound healing. Thus, it is important to
understand the physiology of wound healing. The
wound healing process occurs in three distinct phases:
(1) the inflammatory phase, (2) the proliferative or
granulation phase, and (3) the differentiation or matura­
tion phase.
The inflammatory phase (days 0-5) begins immedi­
ately after wounding and within 1 to 2 hours; there is a
release of vasoactive substances including histamine,
serotonin, and cytokines. These substances cause an
increase in local vessel permeability leading to an
increased exudation of plasma. The leaky capillaries
allow cells such as T lymphocytes, leukocytes, neutro­
phil granulocytes, monocytes, and macrophages to reach
the wound area. Neutrophils (polymorphonuclear leu­
kocytes) predominate in the wound during the first 48
hours after wounding. The polymorphonuclear leuko­
cytes provide a nonspecific cellular defense that is the
initial protection against wound infection. The nuclei of
neutrophils contain proteolytic enzymes that facilitate
cleaning of the wound and phagocytosis of bacteria.
Following the neutrophils, macrophages start to migrate
into the wounded area and predominate by day 4. The
macrophages’ main role is to phagocytose debris and to
digest bacteria. At the fourth day of wound healing,
fibroblasts begin to appear. During this early phase of
wound healing, the tensile strength of the wound is
minimal and is the result of the fibrin coagulum in the
wound bed.1
In parallel with the changes occurring deep within
the wound, the superficial epithelium also undergoes
changes. The epidermis adjacent to the wound edge
begins to thicken within 24 hours after injury. Basal
cells at the margin of the wound release their attach­
ment to the dermis, enlarge, and migrate across the
wound surface to cover the wound. This is possible
because the cells undergo a series of rapid mitotic divi­
sions, resulting in migration of the new cells by moving
over one another until the wound bed is completely
covered by epithelium. Re-epithelialization is usually
complete in less than 48 hours in the case of well-
approximated wounds.
When a wound becomes infected, there is a failure to
progress from the first to the second stage of wound
healing. Bacteria or foreign bodies within the wound
promote the persistence of neutrophils. With continued
neutrophil degranulation and prolonged phagocytosis,
there is an accumulation of partially digested material,
which is the origin of pus. Furthermore, there is delayed
synthesis of critical structural proteins such as collagen.
The infected wound will therefore not progress to
maximum structural integrity until the infection has
resolved.
In the absence of significant infection or wound con­
tamination, the second stage of wound healing begins.
The proliferative or granulation phase (days 6-14) is
characterized by the formation of granulation tissue in
the wound. Granulation tissue consists of a mixture of
cellular elements, including fibroblasts and inflammatory
cells, along with newly formed capillaries contained
within a matrix of collagen, fibronectin, and hyaluronic
acid. Early in the second phase, there is a rapid increase
in the numbers of fibroblasts. The increase is secondary
to an influx as well as in situ production of fibroblasts.2
Structural proteins required for wound repair are
pri­marily synthesized by fibroblasts. Most important,
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42
SECTION I  FUNDAMENTALS
SURGICAL TECHNIQUE
Local Anesthesia
The pharmacologic action of local anesthetics is to block
nerve impulses by disrupting the permeability to sodium
during an action potential. The interval between an anes­
thetic injection and its influence on the action potential
is dependent on the pharmacokinetics of the drug used
and the dosage administered. There are significant dif­
ferences in potency and duration between various anes­
thetic agents. An agent’s potency and length of action
depend on its level of hydrophobicity.7 When the agent
is mixed with epinephrine, the resulting vasoconstriction
increases the time required for clearance of the agent.
This reduction in clearance rate increases the agent’s
duration of action and decreases the total dosage required
to achieve an effective nerve block. Many surgeons use
anesthetics containing epinephrine for the added benefit
of improved hemostasis.
The core chemical structure of local anesthetics is an
amine connected to an aromatic end. The amine end is
hydrophilic, and the aromatic end is lipophilic. Changing
the amine or aromatic end alters the pharmacokinetics of
the drug. There are two classes of local anesthetics based
on variations at the amino end: amino amides and amino
esters.8 The class of amino amides includes lidocaine,
mepivacaine, and bupivacaine. The amino esters group
includes tetracaine, cocaine, and benzocaine.
Lidocaine is the most frequently used infiltrative local
anesthetic. It is available in a variety of concentrations. A
1% solution is commonly used with or without epineph­
rine. With a rapid onset of action, it is an ideal choice for
simple soft tissue surgery. Bupivacaine has a longer dura­
tion of action than lidocaine and thus may be more
appropriate for complex wounds requiring prolonged
repair times. The author (B.C.M.) prefers a 1 : 1 mixture
of 0.5% bupivacaine (Marcaine) and 1% lidocaine with a
total concentration of 1 : 100,000 epinephrine. If a surgi­
cal procedure is to occur without general anesthesia, 10%
by volume of an 8.4% bicarbonate solution is included in
the anesthetic mixture. This mixture produces an excel­
lent rapid-onset anesthesia with long-term analgesia.
The addition of bicarbonate buffers the solution and
decreases injection discomfort.9
The method of infiltration will vary by the site of
injection. Wherever possible, selective nerve blockade
should be employed to reduce the discomfort of diffuse
injection. Infraorbital, supraorbital, and mental nerve
blocks will provide excellent regional anesthesia for facial
soft tissue procedures. For diffuse infiltration, several
factors can reduce injection discomfort: slow injection
rate, use of small-bore needles (27-gauge or higher),
room-temperature injection fluid, and injection with use
of small-volume syringes.
During infiltration, the surgeon must avoid intravas­
cular injection. This complication can be minimized by
frequent aspiration during introduction of the local
anesthetic. Inadvertent intravascular administration can
lead to lidocaine toxicity. Central nervous system lido­
caine toxicity occurs first. The initial manifestations are
excitatory, such as tingling, numbness, mental status
fibroblasts produce large quantities of collagen, which
makes up the majority of the extracellular wound matrix.
It is this matrix that is responsible for the tensile strength
of scar tissue. The collagen is initially deposited in a
disorganized fashion. Through cross-linking, the indi­
vidual collagen fibrils are subsequently reorganized into
regularly organized bundles. The new collagen array is
oriented along the lines of mechanical stress in the
healing wound. The process of fibroblast proliferation
and synthetic activity is termed fibroplasia. Revascular­
ization of the wound proceeds in parallel with fibropla­
sia.3 Capillary buds sprout from blood vessels adjacent to
the wound and extend into the wound space. With con­
tinued growth, the new vessels eventually branch at their
tips and join to form multiple capillary loops. With for­
mation of capillary loops, blood flow recommences. New
sprouts then extend from these loops to form an active
capillary plexus.
The differentiation or maturation phase is the third
segment of wound healing. This occurs from day 15 to 1
year postoperatively and beyond. During this period,
there is a gradual egress of fibroblasts and macrophages.
Overall, the wound becomes less vascular. Collagen
fibers progress on the continuum from disarray to orga­
nization. As the collagen becomes more organized,
wound strength continues to improve; 45% of normal
wound strength is achieved by day 70 and 50% by day
120.4 In general, with optimal wound healing, scar tissue
strength approaches 80% of the original tissue strength
before wounding. Many factors contribute to normal
wound healing; these are listed in Table 4-1. An under­
standing of these factors assists successful primary wound
closure.
Investigators have used their understanding of wound
healing science to guide novel therapies. Lee et al5 showed
that the use of laser therapy (intense pulsed light) or
microneedle techniques could increase collagen deposi­
tion during the wound healing response. An increase in
collagen deposition tended to result in improved scar
appearance and overall wound healing. Other investiga­
tors have shown a decrease in the incidence of scar hyper­
trophy and an improvement in wound healing by use of
lasers to treat scars after surgery.6 Kim et al5 showed that
three postoperative treatments of suture line scars with
the erbium : glass laser (1550 nm) dramatically improved
the appearance of thyroidectomy scars.
TABLE 4-1  Factors Affecting Wound Healing
Local Factors
General Factors
Blood supply
Age
Denervation
Endocrine function (pancreas,
thyroid)
Fluid collection
Drug therapy (anti-inflammatory,
cytotoxic)
Infection
Sepsis
Previous or concurrent
irradiation
Major organ failure (pulmonary,
cardial, hepatic, renal)
Mechanical stress
Obesity
Surgical technique
Malignant disease