Plastic Surgery Volume 1 Principles 4th

187
Clinical wound management
Diagnosis/patient presentation
The preoperative evaluation should include a thorough medical
history, a social history that includes determining who or how wound
care or postoperative care will be provided, pulse exam if the
wound is on the lower extremity, and a nutritional assessment. If the
patient is diabetic, then hemoglobin A1c should be checked. Protein
synthesis, especially collagen, is essential to healing and pre-
albumin is a good basic indicator of protein synthesis capacity.
However, it is an acute phase reactant, so it will be depressed
during concomitant episodes of sepsis or other generalized
inflammatory response. To address this, pre-albumin levels can be
followed serially as often as 2 times per week (half-life is 2 days
compared to albumin with a half-life of 20 days) as it should rise as
the inflammatory state subsides or with initiation of protein
supplementation. The steady state pre-albumin value is an indicator
of the patient’s nutritional status and has been shown to correlate
with clinical outcomes.212
Patient selection
Every surgical patient is a wound patient once the scalpel cuts the
skin. The prudent surgeon will optimize conditions for good wound
healing and surgical outcomes by preparing the patient and the
wound bed for surgical closure.
Treatment (wound-healing specific)
1. If protein malnutrition is present it is reasonable to assume other
nutritional factors are also depleted. Multivitamin and essential
element supplementation should be included in the nutritional
optimization plan.
2. For patients on a chronic glucocorticoid medication regimen,
vitamin A supplementation can overcome some of the
detrimental effects of these steroids on wound healing.213 It can
be given for 2 weeks typically at 10 000 IU per day and should
be started immediately postoperatively for surgical patients.
3. Optimize glucose control depending on results of hemoglobin
A1c or blood glucose monitoring. Elective cases should be
postponed in patients with poorly controlled diabetes as there is
abundant literature indicating the poor surgical and wound-
healing outcomes associated with poor glucose control.
4. Debridement must be adequate to remove all devitalized or
infected tissue otherwise it delays progression from the
inflammatory to the proliferative phase of wound healing (see
section on inflammatory phase).
5. All open wounds must be examined by probing with a finger
and if not possible then a cotton tip applicator to make sure
there are no foreign bodies, underlying bony injuries, or fistulous
tracts.
6. Wound beds must be free of infection prior to closure or have
ongoing treatment for infection at the time of surgical closure to
prevent wound recurrence. Weekly wound debridement is a
good clinical practice to achieve this objective.
7. Optimize perioperative tissue perfusion conditions for good
wound healing outcomes* – the following recommendations are
supported by level 1 evidence and are especially useful for flap
patients.
a. Maintain normothermia (≥36°C) intraoperatively –
significantly decreases the rate of postoperative wound
infection214
b. Provide adequate fluid resuscitation intraoperatively and
postoperatively – increases tissue oxygenation and capillary
blood flow.215 For open laparotomy cases patients were
given 16–18 ml/kg per hour during surgery.
c. Perioperative administration of supplemental oxygen, such
as 0.8 fraction of inspired oxygen (FiO2) given
intraoperatively and 2 hours postoperatively, is sufficient to
significantly decrease postoperative infection rates, length of
stay, and mortality. However, these results can only be
achieved when the patient is normothermic and adequately
perfused/intravascularly replete.216
Outcomes/prognosis/complications
1. The expected outcome for a wound that heals by primary intent
is that the incision is sealed by 24–48 hours because of fibrin
deposition in the wound. At that point the wound progresses to
the proliferative phase of healing.
2. The prognosis for an uncomplicated wound that heals by
primary intent is that the incision will acquire tensile strength at
the following rate: 10% at 2 weeks, 30% at 4 weeks and 80% at
6 weeks compared to intact normal skin. Maximal tensile
strength of the incision is achieved at 6 weeks after closure and
thus never achieves the same tensile strength as intact skin.217
3. Infection is a common and highly undesirable complication for
wounds or surgical procedures. The expected rate of surgical
site infection218 can be roughly estimated using the wound
classification as defined by the Centers for Disease Control.
a. Class I/Clean – An uninfected operative wound in which no
inflammation is encountered and the respiratory, alimentary,
genital, or uninfected urinary tract is not entered. In addition,
clean wounds are primarily closed and, if necessary, drained
with closed drainage. Expected infection rate: 1–2%
b. Class II/Clean-contaminated – An operative wound in which
the respiratory, alimentary, genital, or urinary tracts are
entered under controlled conditions and without unusual
contamination. Specifically, operations involving the biliary
tract, appendix, vagina, and oropharynx are included in this
category, provided no evidence of infection or major break
in technique is encountered. Expected infection rate: 3%
c. Class III/Contaminated – Open, fresh, accidental wounds. In
addition, operations with major breaks in sterile technique
(e.g., open cardiac massage) or gross spillage from the
gastrointestinal tract, and incisions in which acute, non-
purulent inflammation is encountered are included in this
category. Expected infection rate: 6%
d. Class IV/Dirty-infected – Old traumatic wounds with retained
devitalized tissue and those that involve existing clinical
infection or perforated viscera. This definition suggests that
the organisms causing postoperative infection were present
in the operative field before the operation. Expected
infection rate: 7–13%
4. Risk factors for surgical site infection219 include:
a. Patient characteristics
i. Age
ii. Obesity
iii. Smoking
iv. Diabetes
v. Nutritional status
vi. Colonization with microorganisms
vii. Altered immune response
viii. Co-existing infections at a remote body site
ix. Length of preoperative stay
x. ≥3 diagnoses at the time of discharge
Clinical wound management
Clinical vignette – acute wounds and elective surgical patients
Continued

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CHAPTER 13 • Wound healing
b. Operative characteristics
i. Abdominal operation
ii. Operation lasting longer than 2 hours
iii. Wound class III or IV
c. Surgical technique
i. Poor hemostasis
ii. Failure to obliterate dead space
iii. Tissue trauma
5. Incision dehiscence/wound recurrence – occult biofilm infection
(see miR regulation of skin barrier functions)
a. Determination of wound closure – the skin as an organ has
3 primary functions: thermoregulation, prevention of
evaporative water loss, and to serve as a barrier to
infections. Wounds that have occult biofilm infection will
appear closed, but the skin will be functionally defective with
elevated levels of transepidermal water loss (TEWL – see
non-invasive imaging modalities). Channels in the cells that
let water out of the skin will also let bacteria into the skin.
The finding of elevated TEWL is most likely to occur in the
clinical setting of surgical closure of wounds with pre-
existing biofilm infection.
b. Unrecognized soft tissue or bony infection, especially occult
biofilm infection, is a suspected cause for a significant
number of flap dehiscence/wound recurrence outcomes.
Biofilm-producing bacteria express high levels of
ceramidase that enzymatically digests skin lipids.220
Adjunctive therapy with topical antibiotics or biofilm-inhibiting
dressings (see section on Electroceuticals) at the time of
debridement along with systemic antibiotics may mitigate
the risk for postoperative biofilm infection.
c. Measurement of C-reactive protein and erythrocyte
sedimentation rate can be used to screen for osteomyelitis
preoperatively (if elevated, confirm diagnosis with imaging
studies). Serial measurements with an anticipated decrease
in these inflammatory markers can be used to monitor
response to therapy.
Diagnosis/patient presentation
Patients with diabetic foot ulcers commonly present with a classic
triad of clinical findings: ischemia, neuropathy and foot deformity. The
ulcers are frequently initiated by local trauma where the patient cannot
sense the injurious event because of underlying sensory neuropathy.
For this reason diabetics are instructed never to go barefoot. Pressure
from poorly fitting footwear because of foot deformity is another
common initiating event. An early sign of pressure on the foot is the
development of a callus, which should be interpreted as impending
foot ulceration if there is no intervention to off-load the pressure.
Development of foot deformity is attributable to several factors.
Neuropathy contributes to the development of Charcot changes in the
midfoot with osteopenia, fractures/dislocations, and collapse of the
arch. The metatarsal heads become prominent with extension of the
toes at the metatarsal phalangeal joints because of motor neuropathy
of the intrinsic foot muscles (Fig. 13.20). Elevated glucose levels
cause glycosylation of the Achilles tendon that limits excursion. There
is decreased range of motion with foot dorsiflexion, which affects gait
mechanics. Normally there is a heel strike and then rolling up onto the
ball of the foot as a person progresses through their stride. The loss
of foot dorsiflexion results in a foot strike that is more like a peg with
the forefoot absorbing more of the impact during the stride than
normal thereby leading to forefoot ulceration. The risk for forefoot
ulceration is increased when metatarsal heads are prominent. The
combination of elevated glucose and diseased vaso nervorum is
thought to be responsible for the motor and sensory neuropathies
that are observed in these patients, but it also affects autonomic
nerves. There is loss of vasomotor regulation, arteriovenous shunting,
and when combined with microangiopathy (thickened basement
membrane, thrombosis) results in ischemia at the areas of tissue
injury. This means that a patient can present with a pink foot with
palpable pulses and a wound that is actually not well perfused.
Patient selection
Prior to any non-emergent surgical procedure, patients should have
hemoglobin A1c checked and glucose control optimized. All
patients need a thorough vascular exam to determine whether there
is adequate blood flow to the foot to support wound healing prior to
any bedside debridement or non-emergent operative surgical
procedures. Patients with inadequate blood flow need
revascularization to achieve a closed wound.
Treatment
1. Deformity – off-loading interventions are an essential part of any
treatment plan and can include
a. Complete non-weight bearing – e.g. crutches or wheelchair
b. Total contact casting – not removable and changed weekly
by a healthcare professional
c. Removable cast walker – e.g., walking boot, cast shoe
d. Modified footwear – required to heal and prevent ulcerations in
patients with foot deformity, refer to pedorthotist for evaluation
2. Infection – risk for infection increases the longer the wound is open
a. Glucose control is essential – poor glycemic control results
in impaired macrophage function, inability to resolve
inflammation (see section on resolution of inflammation) and
an open wound stalled in the inflammatory phase of healing
b. Osteomyelitis
i. If bone is exposed, the likelihood of infection/
osteomyelitis is 80%
ii. Infected bone should be debrided
c. Biofilm – bacteria in a biofilm state are tightly adherent to
the wound surface
i. If bone is exposed the bacteria will adhere to bone
causing osteomyelitis that cannot be treated with
antibiotics alone. Surgical debridement along with
antibiotics is required to eradicate the infection.*
ii. The presence of biofilm will result in a chronic open
wound – debridement disrupts biofilm, but it will recur,113
therefore good clinical practice is weekly debridement
3. Ischemia – there must be adequate blood flow to support
wound healing
a. Diagnosis
i. Ankle–brachial index with pulse waveforms – must
include pulse waveforms as index values can be falsely
elevated because of atherosclerotic disease of the
arteries (ABI >1.2)
ii. Toe–brachial index – detects vascular obstruction distal
to the ankle, should be used for all ulcers located on the
*Hints and tips – One way to optimize postoperative conditions for successful flap
surgery is using the following regimen: maintenance IV at 2 ml/kg/hr and 4 liter
oxygen per nasal cannula for 24 hours postoperatively. Keep the room warm (if in
a single room) with the temperature set at 80°F (26.6°C) or keep patient covered
and warm until discharge. This promotes vasodilation, optimal perfusion and O2
delivery to the flap. It will also increase collagen deposition for wound healing and
decrease risk for infection.
Clinical vignette – diabetic foot ulcer (DFU)

189
Clinical wound management
foot and should include pulse waveforms. Adequate
perfusion is a TBI >0.6
iii. Transcutaneous oxygen measurement (TcOM) – closest
measurement of tissue perfusion near wound. It gives
absolute values of tissue oxygenation in mmHg, so
results are easy to interpret. Adequate perfusion is
≥30 mmHg
iv. Skin perfusion pressure – occludes blood flow and
measures the opening pressure at which perfusion first
returns to the cutaneous microcirculation after controlled
release of the occlusion. It combines the use of a laser
Doppler and a pressure cuff. Adequate perfusion is
≥30 mmHg
v. Angiography – may miss occlusion of perforators off
axial vessels in the lower extremity
vi. Laser speckle – provides a dynamic image of blood flow
b. Treatment
i. Surgical revascularization
ii. Stenting – for smaller vessels below the knee just need
patency long enough to get wound healed
iii. Hyperbaric oxygen (HBO) – can be used for patients
who are not candidates for surgical revascularization or
in preparation for flap or graft
4. Surgical interventions
a. Weekly bedside debridement is associated with improved
healing outcomes221
b. Achilles tendon lengthening will promote healing of
forefoot ulcers in patients with less than 10 degrees of
passive ankle dorsiflexion with the knee flexed and
extended222,223
c. Successful surgical closure with a flap or graft can be
achieved when the wound bed is free from infection,
the wounded area on the foot is appropriately off-loaded,
there is adequate blood supply to support healing, and
the patient is nutritionally replete with good glucose
control.
5. Advanced therapies
a. HBO – stimulates angiogenesis and eradicates infection
from specific pathogens. Patients with DFU that qualify for
HBO treatment are Wagner grade 3 or higher AND have
failed to improve after at least 30 days of standard therapy.
Meta-analysis indicates that for every 4 patients treated with
HBO, 1 major amputation, i.e. below-knee or above-knee
amputation, would be prevented.224
b. Engineered skin – e.g. Apligraf® or Dermagraft®
c. Extracellular matrix products – e.g. Promogran Prisma®
d. Growth factors
i. Recombinant platelet derived growth factor-BB –
Regranex™ is the FDA-approved version of the
growth factor indicated for use in diabetic foot ulcers.
However, it was given a boxed warning by the FDA in
2008 for an increased risk of malignancies observed
distant to the site of application in patients treated with 3
or more tubes. It is no longer used and serves as a
reminder of the potential off-target effects of growth
factors.
ii. Autologous platelet gel (APG) is a cell-based therapy
that delivers growth factors and cytokines to the wound
through topical application to the wound bed. The data
is mixed regarding APG efficacy and level 1 evidence is
not available. The challenge with APGs is titrating the
level of growth factor and cytokine release to have it fall
within a therapeutic range.
Outcomes/prognosis/complications
1. Validated diabetes foot ulcer severity scores225,226
a. Wagner grade
i. Grade 0: No open lesions; may have deformity or
cellulitis
ii. Grade 1: Superficial ulcer, partial or full-thickness
iii. Grade 2: Ulcer extension to ligament, tendon, joint
capsule, or deep fascia; no abscess or osteomyelitis
iv. Grade 3: Deep ulcer with abscess, osteomyelitis,
tendonitis or joint sepsis
v. Grade 4: Gangrene localized to portion of forefoot or heel
vi. Grade 5: Total foot gangrene
b. University of Texas – stage is the more sensitive prognostic
indicator
i. Stages

I. Stage A: No infection or ischemia

II. Stage B: Infection present

III. Stage C: Ischemia present

IV. Stage D: Infection and ischemia present
ii. Grading

I. Grade 0: Epithelialized wound

II. Grade 1: Superficial wound

III. Grade 2: Wound penetrates to tendon or capsule

IV. Grade 3: Wound penetrates to bone or joint
2. Prognosis
a. Correlates with ulcer severity – worse prognosis, e.g. time to
heal and risk for amputation, with increasing severity
b. The average diabetic foot ulcer is open for 12 months
c. Presence of end stage renal disease (ESRD) worsens
prognosis
3. Complications – amputation is the feared complication. The
prognosis for patients getting amputations is worse than many
types of cancer. Amputation is considered preventable by CMS
if patients receive good foot care and it is used as a quality
indicator for population-based healthcare.
a. 80% of amputations in patients with diabetes mellitus are
preceded by foot ulceration
b. Survival rate after below-knee amputation
i. Without ESRD: 1 year = 72.5% and 5 year = 35%
ii. With ESRD: 1 year = 54.6% and 5 year = 16%
c. Survival rates for diabetic patients after above knee
amputation
i. Without ESRD: 1 year = 48% and 5 year = 16%
iii. With ESRD: 1 year = 26.8% and 5 year = 8.2%
*Hints and tips – Use resorbable antibiotic-impregnated beads in the wound after
resection of infected bone to achieve a sustained release of high levels of antibiot­
ics directly at the site to prevent recurrent biofilm infection, osteomyelitis and flap
dehiscence (Fig. 13.21). A common approach is to use 1 g vancomycin and 1.2 g
tobramycin mixed in with the bead material (Stimulan®, Novartis). Serum levels
should be checked postoperatively and if levels are significantly elevated irrigate
through a closed suction drain to get the beads to dissolve.

190
CHAPTER 13 • Wound healing
Diagnosis/ patient presentation
VLUs are present in 1% of the population.5 Important antecedent
events are a history of major lower extremity trauma, deep vein
thrombosis (DVT), varicose veins, and obesity. VLUs are caused by
incompetence of the venous valves in the leg resulting in a static
column of blood pooling in the lower extremity. The venous
hypertension causes an increase in the number of dermal capillaries
in the skin with increased capillary pressure and increased capillary
permeability. This leads to extravasation and perivascular deposition
of blood and fibrinogen/fibrin. The fibrin barrier prevents oxygen
diffusion out of the capillary beds into the surrounding soft tissues
resulting in ischemia, lipodermatosclerosis, and ulceration.227 Tissue
affected by lipodermatosclerosis is stiff, friable, ischemic, and heals
poorly. Patients will complain of aching, itching, heaviness,
tightness, pain or muscle cramps. The ulcers are superficial with
irregular borders, usually located near the medial malleolus with
surrounding hemosiderin deposits and lipodermatosclerosis. There
may be copious drainage from the ulcers as well. The diagnosis of
VLU can be confirmed with non-invasive vascular studies. Duplex
ultrasound with proximal compression of the vein or Valsalva
maneuver to look for venous reflux is the gold standard for
diagnosis with plethysmography as an alternative method if reflux
studies are inconclusive. Venography, helical venous CT and MR
have also been used to establish the diagnosis. Patients with VLU
have an increased risk for thrombotic events, especially with a
personal or family history of thrombotic events, early onset VLU prior
to age 50, and recurrent or recalcitrant VLU.228,229
Patient selection
All patients must be evaluated for peripheral artery disease, which is
present in at least 30% of patients with VLU. The presence of
peripheral artery disease changes the management of patients with
VLU. The Society for Vascular Surgeons and American Venous
Forum recommend laboratory evaluation for thrombophilia in
patients with a history of chronic or recurrent VLU.230
Treatment
It is important to remember the VLU is the symptom and the
disease is venous valvular incompetence. Treatments directed
toward the ulcer will not cure the disease.
1. Compression is the mainstay of therapy – patients with VLU
should understand it will be needed constantly and forever.
Compression cannot be used when the patient has significant
peripheral artery disease (ABI <0.7 or >1.2). A toe–brachial index
>0.6 or a transcutaneous oxygen measurement >30 mmHg
indicates adequate arterial flow to use compression therapy.
a. Graduated pressure compression stockings should be worn
daily when the patient does not have a VLU.
b. 4-layer compression wraps changed weekly can be used
when VLU is present. A long-lasting topical antimicrobial
dressing can be placed on the ulcer beneath the
compression wrap if the VLU is infected.
c. Intermittent pneumatic compression stockings can be used
by persons who cannot wear compression stockings.
2. Elevate extremity – keep affected legs elevated when possible
and especially when not using compression, as edema limits
oxygen diffusion to the tissues.
3. Increase calf muscle pump functions – targeted exercises can help.
4. Surgical interventions
a. To treat valvular incompetence – only effective when disease
is limited to superficial venous system, should not be used
when deep venous disease, DVT, or obstruction are present
as it can make ulcers more recalcitrant
i. Subfascial endoscopic perforator surgery – procedure of
choice
ii. Superficial venous ablation
iii. Endovenous laser ablation
iv. Valvuloplasty
b. Wound debridement – VLU are notorious for polymicrobial
infection (suspected biofilm infection); routine weekly
debridement is recommended to disrupt and help prevent
biofilm infection231
c. Tissue biopsy – ulcers present for longer than 3 months or
which fail to respond to treatment after 4–6 weeks should be
biopsied to evaluate for malignancy or other atypical causes
of leg ulcers such as vasculitis, or cutaneous manifestations
of systemic disease
d. Free tissue transfer – can provide durable treatment for
large recalcitrant ulcers by improving venous hemodynamics
and removing all lipodermatosclerosis-affected tissues that
prevent ulcer healing.232,233
Outcomes/prognosis/complications
1. Contact dermatitis – because of multiple prolonged exposures
to topical agents
2. Soft tissue necrosis – when compression is applied to patients
with concomitant arterial insufficiency
3. Malignancy – squamous cell and basal cell carcinomas are
most common
4. Infection* – frequently polymicrobial, routine use of topical
antimicrobial dressings is not recommended without a
diagnosed wound infection
5. Deep venous thrombosis – stasis and inflammation are major
contributing factors
6. Ulcer recurrence – approximately 50% of VLU recur within 10
years230
*Hints and tips – Hydrofera Blue® (Hollister, Inc.) is a foam dressing with gentian
violet as the active antimicrobial agent. The foam dressing is absorbent, can be
left in place under the compression wrap and gentian violet has broad antifungal
and antibacterial activity (including MRSA and Pseudomonas spp.)234
Clinical vignette – venous leg ulcer (VLU)
Wound healing occurs as a well-coordinated series of biologic
events. Clinical manifestations of dysregulated wound healing
include: hypertrophic scars, keloids, and prominent granula­
tion tissue, as examples of exuberant healing, while chronic
wounds are stalled in the inflammatory phase. Every time a
surgeon takes a scalpel to skin a wound is created. Understand­
ing the fundamentals of wound healing will enable the surgeon
to optimize conditions for good surgical outcomes. First and
foremost attention should be paid to preparing the patient and
the wound bed for healing or surgical coverage/closure.
Wound bed preparation
Patients with chronic open wounds typically have multiple
comorbidities and these need to be medically optimized to
ensure patients have the capacity to heal their wounds.
Smoking cessation, adequate protein nutrition, and good
glucose control as determined by hemoglobin A1c levels
are essential. Patients with autoimmune or other inflamma­
tory conditions need to have these controlled as well. For
patients on chronic steroid therapy perioperative vitamin A

191
Clinical wound management
Fig. 13.21  Placement of absorbable antibiotic impregnated beads over debrided
bone with known osteomyelitis
Table 13.1  Medical comorbidities that impair wound healing
Malnutrition
Smoking
Renal failure
Radiation
Diabetes – poorly controlled
Heart failure
Hemoglobinopathies
Immunosuppression
Autoimmune inflammatory conditions – poorly controlled
supplementation may be beneficial to support wound epithe­
lialization (Table 13.1).235
The physical examination of any wound, whether acute or
chronic, must include palpation. Wounds should be probed
for underlying fractures, retained foreign bodies, exposed
hardware, communication with other joint spaces or body
cavities and the presence of heterotopic bone when examining
pressure ulcers. The presence of tunnels or undermining
should be documented in the medical record. The periwound
skin should be examined, looking for signs of additional
injury such as induration, violaceous discoloration, redness,
swelling, and signs of maceration including moist red skin
with superficial ulceration (Fig. 13.22) and white rolled borders
of the wound edge, called epibole (Fig. 13.23). One should
look for the cardinal signs of infection (rubor, dolor, calor,
tumor); and for chronic wounds pain has also been recognized
as an indicator of potential underlying infection.236,237 However,
Fig. 13.22  Moisure-associated skin damage
Fig. 13.23  Epibole.
Fig. 13.20  Diabetic foot ulcer with multiple associated foot deformities including
arch collapse, prominent metatarsal heads and claw deformity/hyperextension of
toes.

192
CHAPTER 13 • Wound healing
Wound dressings
The selection of a wound dressing needs to be individual­
ized to each patient. The ideal dressing according to the
British National Health System is one that can absorb and
contain exudate, does not leave particulate contaminants in
the wound, provides thermal insulation, does not traumatize
the wound bed when removed, is impermeable to water and
bacteria, minimizes the frequency of dressing changes, and
provides pain relief and comfort when used.241 In general,
inexpensive basic options for wound dressing should be tried
first. If wounds fail to respond after wound bed preparation
and use of first line therapies, then practitioners should pro­
gress to using advanced therapies. It should be noted that
the Cochrane Database of Systematic Reviews has performed
many meta-analyses on wound healing and states that
there is no evidence to indicate the superiority of any type
of wound dressing.241–243 A list of the different types of first
line dressings and the indication for their use is included in
Table 13.2.
Advanced therapies in wound healing
Growth factors
These are soluble factors that stimulate cells such as fibroblasts
and keratinocytes via transmembrane glycoprotein recep­
tors.244 Platelet-derived growth factor (PDGF) is most studied
among the growth factors and a recombinant version (rhPDGF)
showed positive effects in a randomized double blind study
of DFUs.245 rhPDGF marketed as Regranex® (also called beca­
plermin) is the only FDA-approved growth factor product in
the market specified for use in DFU treatment. This therapy
has been shown to rely on ROS for biological functionality.246
It has also been shown to accelerate wound healing in irradi­
ated wounds and abdominal wall separations.247,248 Another
growth factor based product that is considered to be closer to
the natural healing process is the autologous platelet gel
(APG) treatment that is a composite of multiple growth factors
derived from the patient’s own blood. APG has been tested
with chronic skin and soft tissue ulcers, burns, trauma surgery,
etc., and has shown promise.249,250
Extracellular matrix (ECM)
Acellular, collagen rich scaffolds derived from varied sources
such as human or porcine dermis and porcine small intestinal
submucosa (SIS) have been used for various procedures such
as facial reconstruction and abdominal wall repair. AlloDerm®
(human dermis), OASIS® (SIS) and MatriStem® (porcine
bladder submucosa) have all been applied as treatments for
different types of non-healing wounds (DFUs, VLUs and PUs)
and found to accelerate the process of wound healing.251–256
These ECM products are advantageous because they provide
a scaffold containing collagen and additional growth factors
such as TGF-β, VEGF and FGF, which combine to promote
granulation and epithelialization of dermal wounds resulting
in healing. There are also ECM products that do not contain
bioactive growth factors, such as Prisma®, made of oxidized
cellulose and collagen that has been shown to improve healing
rates in diabetic foot ulcers in a small randomized controlled
unless it is grossly apparent that the wound is infected, i.e.,
foul odor, purulent drainage with or without systemic mani­
festations of illness, then diagnosis of wound infection on the
basis of clinical exam alone is unreliable.238 Biofilm infection
of a wound suppresses the host inflammatory response, so
physical signs of infection are not present. All of this informa­
tion needs to be taken into consideration when performing
debridement as part of the wound bed preparation.
Adequate debridement of wounds includes removal of all
necrotic tissue and removal of epibole and periwound fibrotic
tissue as these hyperproliferative cells do not migrate across
the wound surface to promote closure.239 Unroofing areas of
tunneling and undermining, specifically removing skin cover­
ing these areas even if the skin is healthy, needs to be done to
provide adequate care of the wounds and facilitate planning of
surgical coverage. Wound tissue biopsies for culture should be
obtained once debridement is complete to determine whether
bacteria remain in the wound. Sending the excised necrotic
tissue for culture is not informative. Alternatives to sharp
debridement include enzymatic debridement agents such as
collagenase, mechanical debridement using wet to dry dress­
ings, biodebridement using maggots, and non-contact low
frequency ultrasound therapy (MIST® – Alliqua Biomedical).
Ensuring adequate wound bed perfusion and oxygenation
is an absolute requirement for wound healing to occur. Oxygen
is required for respiratory burst to kill bacteria, it is required
for ATP production, cellular energetics, intracellular signaling
and collagen synthesis. Elective debridement of wounds
should not be performed until it has been established that
there is adequate perfusion to support wound healing. For
lower extremity wounds palpation of pedal pulses should
always be the starting point. If pedal pulses are diminished
non-invasive vascular studies such as ankle–brachial index,
toe–brachial index, transcutaneous oxygen measurements, or
imaging modalities that demonstrate blood flow such as laser
speckle, or laser Doppler flowmetry can be used. For those
patients who cannot be revascularized, have multiple comor­
bidities, and are immobile with no functional goals, dry stable
eschar on the heels can be left intact.240 The term dry stable
eschar denotes black eschar tightly adherent to the wound
with no drainage, redness, or odor. These are essentially
treated like dry gangrene that is allowed to auto-amputate as
the wound bed below heals. The eschar should be debrided
if signs of infection develop. Perfusion to wounds should be
considered on an angiosomal basis, i.e., is the perforator
vessel to the skin patent and is the source vessel for the per­
forator patent. If perfusion and oxygenation are poor due to
source vessel obstruction or occlusion, then options for
improving perfusion include peripheral vascular bypass or
endovascular stenting. While permanent patency of stents is
ideal, the objective is to have patency long enough to get
wounds healed and eliminate the risk for limb loss. Reducing
peripheral edema is also an important adjunct to improve
tissue oxygenation as diffusion distance of molecular oxygen
from capillaries is significantly decreased with tissue edema.
If pressure is a contributing etiologic factor then offloading
measures need to be included to enable wound healing. For
diabetic foot ulcers this would include modified footwear,
total contact casting or non-weight bearing on the affected
limb. For pressure injuries this would include the use of
cushions to pad wheelchairs and protective boots to offload
heels for patients who are bed bound.

193
Advanced therapies in wound healing
Table 13.2  Common wound dressings
Dressing
Indications
Examples
Foam – hydrophilic polyurethane fibers absorb
fluid
Light to medium exudate, comfort,
protect against shear
Mepilex® (Mölnlycke)
Antibacterial – all the types of dressings listed here
have antibacterial properties
Infected wounds
Manuka honey, silver, iodine, gentian violet,
chlorhexidine, polyhexamethylene
biguanide (PHMB), antibiotic ointments
Alginate – made from calcium alginate derived
from seaweed, can absorb up to 20 times its
weight in fluid
Highly exudative wounds – requires
secondary dressing
Calcium alginate
Hydrogel – cross-linked gelatin or other insoluble
fibers in solution with high water content
Hydration of desiccated wound bed to
promote healing – requires
secondary dressing
Duoderm® gel (Convatec)
Hydrocolloid – gelatin, pectin or
carboxymethylcellulose bonded to stiff backing
that is impermeable to water and bacteria
Superficial wound with minimal exudate
and no tunnels or undermining,
promotes autolytic debridement
Duoderm® (Convatec)
Hydrofiber – soft absorbent material that turns into
a gel on contact with wound
Use to manage low to moderate
exudate
Aquacel® (Convatec)
Charcoal infused
Odor management
Fungating tumors, foul-smelling wounds
Barrier creams
Protect periwound skin from maceration
or fecal/urine contamination
Zinc oxide, Aloe Vesta® protective ointment
(Convatec)
Protease modulating matrix – collagen substrate
for the proteolytic enzymes present in wounds to
protect wound bed from enzymatic degradation
Chronic wounds, moderate exudate
Promogran™, Promogran Prisma®
(Acelity), Puracol® (Medline), Endoform™
(Hollister)
trial.257 Patients that responded well to the Prisma® product
had decreased levels of MMP-9 and elastase at the wound site
suggesting that the dressing may provide a substrate for enzy­
matic digestion to prevent soft tissue at the wound site from
being targeted and limiting inflammation.
Engineered skin
Since the 1980s, the use of engineered biologic material for
chronic wound therapy has evolved to expedite wound healing
by providing scaffolds and release of growth factors to support
cellular growth and re-epithelialization. Epidermal autografts
were the first to show promise but had drawbacks related to
the lack of a dermal component that have limited their applica­
tions. Apligraf®, a bilayered skin equivalent derived from
neonatal foreskin and grown on bovine collagen matrix,
showed promise in phase III clinical trials for chronic wounds
such as venous ulcer and DFU and is now FDA approved for
therapeutic use in the context of these ulcers.258,259 However,
the allogeneic origin of the cells, growth on bovine collagen
and lack of dermal structures such as hair follicles and sweat
glands add a cautionary note on wide applicability. Derma­
graft® is a cryopreserved, three-dimensional human dermal
substitute composed of human fibroblasts in a dissolvable
mesh with an FDA approval for use in DFUs.260 It has also
shown promise in other applications such as VLU and PU.260
Integra™ is a partial biologic dressing composed of a bovine
collagen matrix and a glycosaminoglycan from shark cartilage
associated with a temporary silicone epidermal sheet.260,261
This is indicated for use in partial or full thickness burn wounds
and non-burn wounds such as VLUs, PUs and traumatic soft
tissue reconstruction over exposed joints and bone.262,263
Oxygen therapy
Hypoxia is a double-edged sword in wound healing and
exists in wounds as a gradient from the center (most hypoxic)
to the periphery (least hypoxic). While hypoxia plays a role
in initiation of neovascularization upon acute exposure,
chronic hypoxia is known to impair angiogenesis.264,265 There­
fore the application of oxygen therapy to promote wound
healing has value and indeed applied systemic hyperoxia
(hyperbaric oxygen therapy (HBOT)) has been shown to
effectively treat necrotizing infections, and increase angiogen­
esis, granulation tissue formation, wound contraction and
secondary closure. There are currently 15 CMS-approved
indications for HBOT treatment (). This involves
enclosing the patient in a special chamber where 100% oxygen
at 2–3 atmospheres of pressure is applied for 60–120 minutes.
The treatment is given 5 days a week for about 10–60 treat­
ments depending upon the type of wound being treated. This
results in saturation of oxygen-carrying capacity of hemoglo­
bin and high levels of dissolved oxygen carried in the plasma.
Dissolved oxygen in the plasma diffuses across the capillary
bed in response to tissue oxygen gradients. This is a highly
specialized treatment modality delivered by physicians and
staff that have had additional training in hyperbaric medicine
and administration of HBO therapy. There are some risks
associated with this treatment including middle ear baro­
trauma with perforation of the tympanic membrane, seizures,
hypoglycemia, and exacerbation of heart failure. However,
the benefits of HBO are significant. A meta-analysis on HBO
therapy for diabetic foot ulcers found that for every 4 patients
that received HBO it prevented 1 major, i.e., below knee or
higher level, amputation.224

194
CHAPTER 13 • Wound healing
Topical oxygen (TO) therapy involves the local application
of 100% O2 at slightly above 1 atmosphere pressure for 90
minutes once a day for 4 consecutive days followed by 3 days
of no treatment. It has been shown to oxygenate superficial
wound tissue up to 2 mm deep266 in the optimal therapeutic
range (40–80 mmHg) that enhanced VEGF expression (unlike
HBOT)267 and angiogenesis in human wounds. This treatment
is typically given to patients in their home. Guidelines for the
selection of patients and application of TO therapy for optimal
use have been defined and suggest that this therapy could be
considered for treatment of refractory wounds.268
Negative pressure wound therapy
Negative pressure wound therapy (NPWT) is a well-known
treatment modality used to promote healing in acute or
chronic wounds. The basic concept of NPWT involves the use
of a moistened foam or antimicrobial gauze dressing, covered
with a transparent adhesive cover, attached to a vacuum
pump that creates a sub-atmospheric pressure environment
to the wound area. The intrinsic mechanotransductive proper­
ties of the skin are modulated for beneficial effects with the
use of this therapeutic modality.269 The extrinsic tensile forces
being applied to the wound surfaces are proposed to (a) cause
shrinkage of wound area because of mechanical contraction,
(b) apply a microstrain that alters the shape and function of
individual cells, (c) remove fluids and reduce edema thereby
inducing a return to osmotic homeostasis and (d) maintain a
moist and stable wound environment which is conducive to
healing.269,270 This therapy can be adapted to meet individual
patient needs in combination with other therapies (antimicro­
bial silver, skin substitutes such as Apligraf® and Integra™
and a wireless electroceutical dressing)270–273 and has been
indicated to be useful in the case of DFU and VLUs.274,275
However, a serious complication associated with this treat­
ment is bleeding and therefore it should not be placed directly
over areas of vascular repair or anastomosis.276
Electroceuticals
An intrinsic electric field and natural direct currents are
present in the skin and are essential for normal regeneration
in lower vertebrates, and their reversal induces degeneration.
The human skin maintains an intrinsic transepithelial poten­
tial (TEP) in the intact skin. When the skin is wounded, the
potential difference between the wound and the surrounding
intact skin generates an endogenous electric field (10–100 µA/
cm2) around and directed into the site of the wound and the
cells within this field respond to the presence of this field.277–282
Electrostimulation (ES) therapy is based on the premise that
an externally applied electric field can then result in an electric
current being driven along the wound surface, enhancing the
endogenous electric field and aiding the healing processes.
This field has been shown to promote several major signaling
cascades that influence the directed migration of numerous
cells (such as keratinocytes, fibroblasts, endothelial cells
and immune cells) that are integral to the wound healing
response.283 Although the concept of ES therapy has existed
for over a hundred years, it has primarily impacted neuro­
nal stimulation (cochlear implants, spinal cord, deep brain
stimulation) and cardiac function (pacemakers) and there are
FDA approvals for many of these applications.284,285 The use
of ES for wound care applications has been slowly gaining
momentum. Several clinical trials have addressed the applica­
tion of various types of electrical stimulation such as direct
current (DC), alternating current (AC), high-voltage pulsed
current (HVPC) and low-intensity direct current (LIDC) for
all types of chronic wounds.285,286 However, some limitations
include ease of application of these treatments and variations
in efficacy of the different ES treatments because of lack of
standardized parameters (voltage, type of current (direct vs
alternating), mode and length of time for treatment) for use.
In 2002, Centers for Medicaid/Medicare Services approved
reimbursement of ES treatments of chronic ulcers that did
not respond to standard therapies.287 The FDA has not yet
approved ES applications for wound care with the exception
of a woven bandage with embedded microbatteries that acts
as a wireless electroceutical dressing (WED).288 Microcell bat­
teries of silver and zinc, activated by a moist environment,
generate an electric field of 0.1–1 V which stimulate wound
healing and provide antimicrobial protection (Procellera™,
Vomaris Innovations). The molecular mechanisms involved in
the enhancement of wound healing by ES have been studied
in vitro. Electric fields generated by this dressing improved
keratinocyte migration via redox-dependent processes289 and
disrupted bacterial biofilm by repressing quorum sensing
and redox-sensitive multidrug efflux pathways.290 This novel
electroceutical dressing, used in conjunction with NPWT
in a randomized clinical trial, decreased the frequency
of dressing change and lowered the cost of the associated
wound care.273
Acknowledgment
Supported by National Institute of Diabetes and Digestive and Kidney
Diseases grant R01 DK076566 (S.R.), National Institute of Nursing
Research grants NR015676 (S.R.) and NR013898 and NR015676 (C.K.S.),
and National Institute of General Medical Sciences grants RO1 GM108014,
GM069589, and GM 077185 (C.K.S.). The authors thank Shomita S.
Mathew-Steiner, PhD for support in writing this article.
40. Martin P. Wound healing – aiming for perfect skin regeneration.
Science. 1997;276:75–81. The healing of an adult skin wound is a
complex process requiring the collaborative efforts of many different
tissues and cell lineages. This review discusses the key signals and
processes that regulate the normal adult cutaneous wound repair.
41. Martin P, Leibovich SJ. Inflammatory cells during wound repair:
the good, the bad and the ugly. Trends Cell Biol. 2005;15:599–607.
50. Khanna S, Biswas S, Shang Y, et al. Macrophage dysfunction
impairs resolution of inflammation in the wounds of diabetic mice.
PLoS ONE. 2010;5:e9539.
70. Carmeliet P. Angiogenesis in life, disease and medicine. Nature.
2005;438:932–936.
86. Banerjee J, Chan YC, Sen CK. MicroRNAs in skin and wound
healing. Physiol Genomics. 2011;43:543–556. MicroRNAs (MiRNAs)
are small endogenous RNA molecules about 22 nucleotides in length that
are capable of post-transcriptional gene regulation by binding to their
target messenger RNAs (mRNAs). This review focuses on the role of
miRNAs in cutaneous biology, the various methods of microRNA
modulation and the therapeutic opportunities in treatment of skin
diseases and wound healing.
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243. Vermeulen H, van Hattem JM, Storm-Versloot MN, et al. Topical
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244. Bennett SA, Birnboim HC. Receptor-mediated and protein
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245. Steed DL. Clinical evaluation of recombinant human platelet-
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246. Sundaresan M, Yu ZX, Ferrans VJ, et al. Requirement for
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247. Shackelford DP, Fackler E, Hoffman MK, et al. Use of topical
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abdominal wound separation. Am J Obstet Gynecol.
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248. Hom DB, Manivel JC. Promoting healing with recombinant human
platelet-derived growth factor–BB in a previously irradiated
problem wound. Laryngoscope. 2003;113:1566–1571.
249. Lacci KM, Dardik A. Platelet-rich plasma: support for its use in
wound healing. Yale J Biol Med. 2010;83:1–9.
250. Roy S, Driggs J, Elgharably H, et al. Platelet-rich fibrin matrix
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251. Shankaran V, Brooks M, Mostow E. Advanced therapies for
chronic wounds: NPWT, engineered skin, growth factors,
extracellular matrices. Dermatol Ther. 2013;26:215–221.
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253. Shi L, Ronfard V. Biochemical and biomechanical characterization
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254. Lev-Tov H, Li CS, Dahle S, et al. Cellular versus acellular matrix
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255. Lecheminant J, Field C. Porcine urinary bladder matrix: a
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256. Harding K, Kirsner R, Lee D, et al. International consensus. Acellular
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257. Gottrup F, Cullen BM, Karlsmark T, et al. Randomized controlled
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258. Falanga V, Sabolinski M. A bilayered living skin construct
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259. Veves A, Falanga V, Armstrong DG, et al. Graftskin, a human skin
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261. Hansen SL, Voigt DW, Wiebelhaus P, et al. Using skin replacement
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262. Gottlieb ME. Management of complex and pathological wounds
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263. Lineen E, Namias NJ. Biologic dressing in burns. Craniofac Surg.
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264. Semenza GL. HIF-1: using two hands to flip the angiogenic switch.
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266. Fries RB, Wallace WA, Roy S, et al. Dermal excisional wound
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267. Gordillo GM, Roy S, Khanna S, et al. Topical oxygen therapy
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268. Gordillo GM, Sen CK. Evidence-based recommendations for the
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269. Wong VW, Akaishi S, Longaker MT, et al. Pushing back: wound
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270. Huang C, Leavitt T, Bayer LR, et al. Effect of negative pressure
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271. Lerman B, Oldenbrook L, Ryu J, et al. The SNaP Wound Care
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273. Ghatak PD, Schlanger R, Ganesh K, et al. A wireless electroceutical
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274. Expert Working Group. Vacuum assisted closure:
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275. Apelqvist J, Bakker K, van Houtum WH, et al. Practical guidelines
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ONE. 2015;10:e0119531.

14 
Scar prevention, treatment, and revision
Michael S. Hu, Elizabeth R. Zielins, Michael T. Longaker, and H. Peter Lorenz
SYNOPSIS
■ Preventing and treating problem scars are vital to patient satisfaction
and good outcomes in all surgical cases, ranging from the most
precise aesthetic work to the most challenging reconstructive
procedures. Understanding how scarring occurs helps to structure our
surgical planning, approach, and technique. In follow-up care,
minimizing scarring can lead to improved form and function as well as
increased patient satisfaction. Even long after recovery, patients with
pathologic or abnormal scarring may seek the expertise of a plastic
surgeon for scar revision. However, even the most experienced
surgeons can attest to the challenges of managing scar tissue in
reoperative surgery.
■ To begin to tackle such obstacles, plastic surgeons have created an
arsenal of tools based on the central tenets of our discipline. Published
in 1957 by Gillies and Millard, The Principles and Art of Plastic
Surgery set out fundamental doctrines of plastic surgery and defined
the foundational knowledge of our field.1 Operative scar treatment and
revision procedures rely heavily on these principles. Ideas such as
diagnosing before treating, making a plan, marking landmarks,
“borrowing” tissue from other areas, and restoring the beautiful normal
represent our approach to the management of scars. Instead of having
a specific operation for each defect, the plastic surgeon is charged
with using these principles to optimize therapeutic options for each
individual patient.
■ To the surgical armamentarium we continue to add our growing
understanding of scar biology. Fetal models have shed light on the
complex factors that determine scarring versus scarless wound
healing. In addition, we have deepened our understanding of the
mechanisms that lead to pathological hypertrophic and keloid scar
formation. Such advances in cell and tissue biology have revealed
many new therapeutic targets, which are currently under active
investigation.
■ Each treatment plan begins with the patient. A good treatment outcome
is rarely achieved without first understanding the patient’s antecedent
experience, current complaints, and future expectations. Here we will
describe important aspects in approaching a scarred patient,
assessing a scar and understanding scar biology. We will then focus
on strategies for preventing, treating, and revising scars. These
strategies are defined by both modern advancements in medicine as
well as time-proven principles of surgery.
Personal and social significance
of scars
For physicians, scars represent an endpoint in wound healing.
For patients, however, scars exemplify something far more
deeply personal and emotional. Scars caused by disease,
violent trauma, or aberrations of development can result in
lifelong physical and psychological burdens. Treating scars
thus requires an understanding of the psychological and
social distress a patient may experience.
Scars may arise from both culturally sanctioned and pro­
hibited practices. Ritual scarring, or cicatrization, was an
important part of identifying tribal belonging in parts of
Africa and Australia.2 In tribal communities in Sudan and
Papua New Guinea, the prevalence of keloid formation in
certain racial groups was exploited for spiritual and cultural
markings. Likewise, the Japanese art of tattoo, or irezumi,
carried sufficient cultural weight as to be banned by the Meiji
government until 1945, when occupational forces again legal­
ized its practice. Today tattooing and, to a lesser degree,
branding and scarification, continue to be a popular form of
self-expression.3
Gender plays a clear role in the effect of scars in society. A
recent study suggested that facial scars in men indicate risk-
taking and bravery, and these men are subsequently perceived
as more attractive.4 The same effect was not found when
observers were shown similarly scarred women. Neverthe­
less, many scars carry negative social implications for both
genders. Studies of quality of life measures in burn patients
reveal that scars cause significant decrease in the quality of
patients’ social and professional life.5 For instance, both
depression and post-traumatic stress disorder (PTSD) have
been identified as potential long-term sequelae, with rates for
PTSD in burn patients ranging from 23% to 45% at 1 year

197
Assessing scars
following injury.6 Risk factors include avoidant coping strate­
gies and pre-existing psychiatric history, as well as hand and
face involvement and burn severity.7 Therefore understanding
the specific aspects of the patient’s life most affected by the
presence of scarring can help direct both medical and non­
medical therapy.
Psychologist Thomas F. Cash described the importance in
reconciling a patient’s “view from the outside” and “view
from the inside” when coping with deformity.8 Understand­
ing the social context and patient’s emotional relationship to
scars is vital to treatment. A potentially useful tool in under­
standing and assessing these variables is Psychological Aspects
of Reconstructive and Cosmetic Plastic Surgery: Clinical, Empiri­
cal, and Ethical Perspectives.9 This title reflects a multidisci­
plinary effort of leading psychologists, psychiatrists, and
surgeons in determining and delivering care to patients with
real or perceived deformities.
History and physical examination
As with the evaluation of most maladies, assessment of a
patient with an unsatisfactory scar begins with a focused
history and targeted physical examination (Box 14.1). While
obtaining the history, the etiology of the scar and relevant
associated factors (e.g. prior dissatisfactory surgery, relation
to violent crime or infection) should be elucidated. In com­
municating with the patient, the treating physician should be
empathetic without attempting to attribute the patient’s
current complaints to care provided by prior treating physi­
cians. This can usually be accomplished by focusing on the
problem at hand and appropriate next steps.
The physical exam includes an assessment of both the scar
and surrounding tissue. With facial scars, attention must be
paid to normal folds and features as determined by the aes­
thetic subunits.10 Examination of other scars on the patient to
determine predisposition to poor scarring can also be helpful.
Evaluation of the scar should include written and photo­
graphic documentation of size, color, and texture. The rela­
tionship of the scar to surrounding structures in motion and
repose should be carefully assessed to determine tethering
and contracture.
Scar formation can cause functional, aesthetic, and emo­
tional problems. Before initiating treatment, the physician
BOX 14.1  Key points
History
Etiology
History of infection
Associated symptoms (pain, itching)
Radiation and steroid exposure
Physical exam
Size, color, texture
Relationship to normal structures
Tethering and contracture
Changes with movement
Table 14.1  The Vancouver Scar Scale
Pigmentation
0
Normal: color that closely resembles the color
of the rest of the body
1
Hypopigmentation
2
Hyperpigmentation
Vascularity
0
Normal: color that closely resembles the color
of the rest of the body
1
Pink
2
Red
3
Purple
Pliability
0
Normal
1
Supple: flexible with minimal resistance
2
Yielding: giving way to pressure
3
Firm: inflexible, not easily moved, resistant to
manual pressure
4
Banding: rope-like tissue that blanches with
extension of the scar
5
Contracture: permanent shortening of the
scar, producing deformity or distortion
Height
0
Normal: flat
1
<2 mm
2
<5 mm
3
>5 mm
(Reproduced from Sullivan T, Smith J, Kermode J, et al. Rating the burn scar. J
Burn Care Rehabil. 1990;11:256–260.)
must take the time to understand and address each of these
elements. The extent of scar should be considered along with
the patient’s goals in getting treatment. Arriving at realistic
targets and expectations may require multiple visits or a
combination of surgery and counseling. Frequently, schedul­
ing a second or third visit to ensure the patient understands
the treatment plan and has realistic expectations prior to
undergoing the planned procedure is in the surgeon’s best
interest.
Assessing scars
Clinical evaluation of a scar is necessary in determining the
best course of treatment and effectiveness of therapy. The
ideal scale for scar assessment should demonstrate validity,
inter-observer reliability, and clinical applicability. Though
multiple objective and subjective assessment tools have been
devised to characterize scars, there is as yet no universal
consensus on scar grading. However, the most frequently
used measure is the Burn Scar Index, also known as the
Vancouver Scar Scale (VSS) (Table 14.1).11 Originally published
in 1990, the VSS is an observer-dependent scale designed to
assess changes in burn scars with maturity and in response to

198
CHAPTER 14 • Scar prevention, treatment, and revision
closure adhesives, and new therapeutic agents for scar
treatment.
A number of instruments have also been used to facilitate
objective assessment of scars. Blood flow has been analyzed
by laser Doppler, while depth and color have been studied by
ultrasound and spectrometry.21 Skin elasticity meters, com­
mercialized for evaluation of scleroderma, have also been
used to examine scars.22 Lastly, three-dimensional systems
have been used in a number of studies to create high defini­
tion and easily reproducible topographic representation of
scars. While these instruments demonstrate a high degree of
accuracy, reliability and clinical utility, the added expense
and additional technical training required have limited them
largely to research settings.
Scar biology
Scar formation is a physiologic response to injured tissue and
reflects the body’s attempt to restore tissue strength and
integrity. The imperfect nature of this process likely reflects a
trade-off of organization for debridement and sterilization,
and results in distinct morphologic differences between
scarred and normal tissue. A mature scar, the final product of
normal wound healing, is characterized by a disorganized
array of collagen and loss of dermal appendages. However,
scars are not static entities. Instead, scar formation is a dynamic
process, beginning at the initial injury and proceeding tempo­
rally through the phases of wound healing to produce a
mature scar (Fig. 14.1).
Normal wound healing is a complex process that can be
roughly divided into three overlapping stages: inflammation,
proliferative matrix formation, and remodeling. Inflamma­
tion, the first stage of wound repair, is characterized by
infiltration of immune cells attracted by various cytokines,
invading pathogens and growth factors towards the wound
site. Platelets also aggregate at the site of injury, resulting in
activation of the coagulation cascade and leading to the for­
mation of a fibrin clot.23 This initial cellular response is aimed
at the establishment phagocytosis of injured cells and hemo­
stasis. In a non-infected wound, inflammatory cells are then
replaced by fibroblasts in the proliferative stage of wound
healing. This phase is characterized by synthesis and secretion
of the extracellular matrix (ECM).
ECM is formed through a highly regulated process of
synthesis, deposition, and degradation by fibroblasts that
migrate to the wound in response to TGF-β, PDGF and other
growth factors. The initial wound environment is largely
composed of fibrin and the glycosaminoglycan hyaluronic
acid. As fibroblasts populate the wound, enzymes degrade the
matrix and collagen is deposited. Cross-linking and organiza­
tion of the collagen ultimately create tensile strength across
the wound. The process of collagen deposition and degrada­
tion is in part determined by the regulation of matrix
metalloproteinases (MMPs), which in turn, are inactivated by
proteins called tissue inhibitors of metalloproteinases (TIMPs).
The balance of MMP–TIMP function remains an active area
of research in wound healing and scar biology.24
At the cellular level, scars are characterized by a lack of
connective tissue organization compared to surrounding
normal tissue architecture. Grossly, the early or immature scar
is red because of its dense capillary network. Over a period
treatment. Scars are assessed based on four variables: pigmen­
tation, vascularity, pliability, and height. Scores are then
assigned across these four variables based on the degree of
variance from normal skin. When applied, the scale can be a
useful tool for prognosis and treatment evaluation. In 1995,
Baryza and Baryza12 found that adding a low-cost instrument
could improve inter-observer reliability. They combined a
ruler, a transparent piece of plastic, and a scoring “cheat
sheet” to aid in measuring, blanching, and determining the
score, respectively.
While perhaps the most commonly used assessment tool,
the VSS is limited by its historical focus on burn scars, lack of
consideration of patient’s own perceptions, exclusion of pain
and pruritus, as well as a lesser applicability to larger scale
heterogeneous scars.13 Other evaluation measures, such as the
Visual Analog Scale (VAS), the Patient and Observer Scar
Assessment Scale (POSAS), the Stony Brook Scar Evaluation
Scale (SBSES), and the MCFONTZL classification system have
been created with varying levels of validation and adoption.14
The large variety of different scales reflects the relative imper­
fection of each individual system.
The VAS assesses parameters such as color, contour, and
texture to correlate intra-observer as well as photographic and
histologic findings.15 The scale can be applied to both burn
and surgical scars. Similarly, the POSAS was developed in
2004 for burns and has since been validated for linear scars.
This scale has the benefit of incorporating patient opinion to
a VSS-like scale and can better assess symptoms such as pain,
itchiness, and thickness.16,17 A third scale, the SBSES, is a
photo-based scale similar to VAS and was initially developed
as a tool for emergency medicine physicians to evaluate
wounds from 5 to 10 days after wounding up to the time
of suture removal.18 The SBSES has since been adapted for
long-term evaluation of scars 3 to 12 months after injury
and has been used as an outcome measure in Food and
Drug Administration-mandated clinical trials.19 Lastly, the
MCFONTZL classification system was developed specifically
for facial trauma (Table 14.2).20 This system incorporates
billing and uses a mnemonic to divide the face into the maxilla,
chin, forehead, orbits, nose, temple, zygoma, and lip. These
scales have been useful in comparing outcomes from conven­
tional versus minimally invasive surgery, use of wound
Table 14.2  MCFONTZL assessment system
A area
MCFONTZL aesthetic unit designation
S Side
T Thickness
Depth of penetration
E Extension
Branching
R Relaxed skin tension
line conformality
Directionality (relaxed skin tension
lines)
I Index laceration
Laceration with maximum continuous
skin interruption
S Soft-tissue defect
K Coding
Current procedural terminology code
(Reproduced from Lee RH, Gamble WB, Robertson B, et al. The MCFONTZL
classification system for soft-tissue injuries to the face. Plast Reconstr Surg.
1999;103:1150–1157.)

199
Conditions of excessive scarring
animal studies (Fig. 14.2). Nevertheless, the tensile strength of
wounded skin only reaches approximately 80% of the tensile
strength of unwounded skin at best. A mature scar, the final
result of tissue repair, is brittle, inelastic, and without skin
appendages such as hair follicles or sweat glands. The cost of
these imperfections is counterbalanced by the benefits of
rapid re-establishment of tissue integrity, debridement, and
sterilization of contaminated wounds.
Conditions of excessive scarring
Wound healing is a tightly regulated process involving cell–
cell signaling and environmental cues. In normal wounds,
repair slows when the dermal defect is closed and epitheliali­
zation is complete. But when appropriate signals are absent
of months, the capillaries regress until relatively few remain
and the red color fades. The scar remodels slowly over months
to years to form a “mature” scar. Mature scars are usually
hypopigmented and appear lighter than the surrounding
skin. However, they can occasionally be hyperpigmented
and darker than the surrounding skin. Hyperpigmentation
is more common in darkly pigmented patients or lighter-
pigmented patients whose scars receive excess sun exposure.
For this reason, surgeons recommend sun protection for
patients with early scars on sun-exposed areas such as the
scalp, face, and neck.
During the remodeling phase, wounds gradually become
stronger with time. Wound tensile strength increases rapidly
from 1 to 8 weeks following initial injury. Thereafter, tensile
strength continues to increase, albeit at a slower pace, and has
been documented to continue to increase up to 1 year in
Fig. 14.1  (A–F) Phases of wound healing. Wounds progress through inflammation, proliferation, and finally remodeling. TGF-β, transforming growth factor-β; PDGF,
platelet-derived growth factor.
Injury
Coagulation
Late inflammation (48 h)
Early inflammation (24 h)
Proliferation (72 h)
Remodeling (weeks to months)
Skin surface
Collagen
Fibroblast
Red blood cell
Platelet
Fibrin
Platelet plug
Neutrophil
Neutrophil
TGF-β
PDGF
Macrophage
Macrophage
Epidermis and
dermis of skin
Wound
D
C
E
F
A
B

200
CHAPTER 14 • Scar prevention, treatment, and revision
Fig. 14.2  Wound tensile strength with time. Wounds reach approximately 80% of
their preinjury tensile strength at 6 weeks. Further gains occur slowly over time and
never achieve 100% preinjury strength.
Platelets
Neutrophils
Macrophages
Fibroblasts
Neovascularization
Lymphocytes
Collagen
Wound strength
Time
24h
80%
100%
48h
3–5 days
6 weeks
1 year
% Healing
% Specific cell, matrix or process
Table 14.3  Types of scar
Appearance
Growth pattern
Cause
Normal mature scar
Hypo- or hyperpigmented, flat
Contracts slowly over time
Normal tissue repair
Immature scar
Red, slightly elevated, sometimes itchy
Turns into mature scar
Normal tissue repair
Hypertrophic
Raised, itchy, painful, confined to its borders
Self-limited, but may take years
Excess mechanical stress
Keloid
Raised, itchy, extending into normal tissue
Continued growth; recurs
Genetic predisposition; can
result from minor trauma
or ineffective, the repair process may continue unabated and
result in surplus scarring. Hypertrophic scars and keloids,
both fibroproliferative disorders of wound repair, are two
examples of this.
In general, both keloid and hypertrophic scar fibroblasts
have an upregulation of collagen synthesis, deposition, and
accumulation. However, the underlying regulatory mecha­
nisms responsible for this excessive repair are still under
investigation. Both profibrotic cytokines such as transforming
growth factor-β1 (TGF-β1) as well as a lack of programmed
cell death, or apoptosis, of activated fibroblasts secreting ECM
components have been implicated in excessive scarring.25,26
For unknown reasons, hypertrophic scars and keloids are
unique to humans and do not naturally occur in other animals.
Normotrophic, hypertrophic, and keloid scars vary little
histologically.27 Pathological scar types are therefore distin­
guished based on clinical characteristics. Hypertrophic scars
continue to thicken and rise instead of flattening and shrinking
like mature scars, but stay within the original scar boundary.
In contrast, keloid scars grow beyond the boundaries of the
initial wound (Table 14.3). Because the timeline from immature
to mature to hypertrophic and keloid scar formation can vary
due to a number of factors, diagnosis is not always clear.
Clinical monitoring of scar evolution with frequent serial
examinations is the most important strategy for diagnosing
Fig. 14.3  (A,B) Hypertrophic scars.
A
B
and treating the problem scar. Early application of treatment
modalities, discussed in depth later in this chapter, can often
prevent further progression and even reverse scar pathology.
Hypertrophic scar
Hypertrophic scars are defined as pathologic scars that have
not overgrown the original wound boundaries, but are instead
abnormally thickened and raised (Fig. 14.3). Hypertrophic
scars are often painful and pruritic. This is thought to be due
to release of proinflammatory neuropeptide substance P from
nerve endings following injury.28 Hypertrophic scars usually

201
Conditions of excessive scarring
keloids from hypertrophic scars. True keloid scars are not
common and occur predominantly in darkly pigmented indi­
viduals, with an incidence of 6–16% in African populations.
This demonstrates genetic predisposition with autosomal-
dominant features. The keloid scar behaves like a benign skin
tumor with continued slow growth, and in the majority of
cases complete excision with primary closure of the defect
results in recurrence.
Keloids consist primarily of collagen. They are relatively
acellular in their central portions with fibroblasts present
along their enlarging borders. Keloids do not, however,
contain a significantly elevated number of fibroblasts. Rather
it appears that collagen deposition outpaces degradation,
allowing the lesion to enlarge.
Keloid formation may be the result of excessive stimulation
or an inappropriate response to stimulation. In vitro studies
find that keloid keratinocytes and fibroblasts respond differ­
ently to growth factors found at the repair site. TGF-β treat­
ment, for example, causes a greater degree of collagen gene
expression in keloid compared to normal wound fibroblasts.32
In addition, a greater degree of profibrotic growth factor
expression occurs in keloids compared to normal wounds.33
Together, these and other studies suggest that keloid
form secondary to excessive tensile forces across the wound
and are most common in wounds across flexion surfaces, the
extremities, breasts, sternum, and neck.
Hypertrophic scarring is a self-limited process and usually
regresses with time. These scars eventually fade in color and
flatten to the surrounding skin level, though the unaided
process may take years. No clear histological differences
between hypertrophic scars and keloids exist. Early studies
found that keloids contained bundles of collagen around focal
nodules of proliferation.29 Later studies, however, refuted this
distinction.
To date, clinical treatment of hypertrophic scars remains
unsatisfactory, and is reflective of our incomplete understand­
ing of mechanisms underlying hypertrophic scar formation.
The creation of consistent and reproducible models for testing
new treatment modalities, particularly animal models of
hypertrophic scars, is key to advancing our knowledge of
hypertrophic scar biology.30,31
Keloid
Scars that overgrow the original wound edges are called
keloids (Fig. 14.4). This clinical characteristic distinguishes
Fig. 14.4  (A–D) Keloids. (With permission from Dr. Shelly Noland.)
A
B
C
D

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CHAPTER 14 • Scar prevention, treatment, and revision
Final closure can be achieved through fine interrupted and
mattress stitches if care is taken for prompt suture removal.
Removing sutures on the face should be performed no later
than 3 to 5 days after placement. If necessary, the wound can
be reinforced with adhesive tape strips at the time of suture
removal. Failure to remove stitches in a timely fashion can
result in a disfiguring railroad scar pattern from stitch marks.
Alternatively, subcuticular stitches or adhesive tissue glue
can be used for final skin apposition. Permanent sutures such
as polypropylene (e.g., Prolene®, Ethicon) or nylon incite less
of an inflammatory reaction than absorbable biodegradable
sutures. However, both permanent and absorbable subcuticu­
lar stitches can be left untied with the ends secured by tape
to avoid granuloma formation around knots. Removal of
permanent subcuticular suture can be aided by interval exter­
nalization of the stitch so the entire stitch does not have to be
pulled through the wound.
To minimize visible scarring, elective incisions are least
noticeable when placed parallel to the natural lines of skin
tension (Langer’s lines) (Fig. 14.6). This placement location
has two advantages: the scar is parallel or within a natural
skin crease, which camouflages the scar, and the location
places the least amount of tension on the wound.
Patient-specific factors
Factors that contribute to poor wound healing can also con­
tribute to poor scarring. Poor nutrition, diabetes, obesity, and
radiation exposure impair healing, and lead to an increased
risk of infection. Patients with these comorbidities are at
higher risk for wound complications and poor scarring.
Medications such as corticosteroids and isotretinoin can
also negatively affect tissue healing. Lastly, though the exact
mechanism has yet to be determined, genetics plays a role
in scarring, as demonstrated most dramatically in keloid
formation.
Wound infections and foreign-body reactions
Wound infections and foreign-body reactions can lead to
wound dehiscence and poor scarring. Increased proinflamma­
tory cytokines may trigger abnormal fibroblast responses.35
Leaving the initial dressing on for 48–72 hours, the time
needed for epidermal closure, is a frequently used strategy to
maintain wound sterility. Efforts to prevent wound infection,
including debridement of any devitalized tissue and admin­
istration of perioperative antibiotics when indicated, should
be a priority.
Adjunct therapy
As previously discussed, minimizing tension has been linked
to decreased scarring.36 Recently, a silicone elastomeric dress­
ing that mechanically off-loads tension has been shown in two
prospective, randomized controlled clinical trials to reduce
scarring after scar revision surgery and abdominoplasty (Fig.
14.7).37,38 The device was applied 1–13 days following closure
of an incision and applied weekly for 12–13 weeks. This
tension off-loading device is a powerful new technology that
represents the first and only level I evidence for scar reduc­
tion. Ongoing research may further demonstrate the effective­
ness of this therapy for hypertrophic scars and keloids.
formation occurs because of increased expression and activity
of proliferative growth factors at the wound site.
Alternatively, a defect affecting the repair process may
result in the absence of appropriate “stop” signals for healing.
In this proposed mechanism, a lack of stop signals in the
wound results in continued and unchecked repair. Studies of
apoptotic cell numbers have found similar amounts of apop­
totic cells at the advancing wound edge in both normal
and hypertrophic scars. In keloid scars, however, decreased
expression of apoptotic genes was found.34 The biology of
keloids continues to raise important questions about what
factors govern normal and pathologic healing.
Prevention
Surgical technique
The molecular regulation of scar formation aside, meticulous
surgical technique continues to be the cornerstone of success­
ful scar minimization (Box 14.2). To begin, the plastic surgical
craft utilizes fine instruments and atraumatic technique to
minimize trauma to tissue. For example, hooks for retraction
and avoidance of double grasping with forceps help prevent
crush injury to delicate tissue.
Obtaining a fine pencil-line scar also relies on relieving
tension on the apposed epidermal edges (Fig. 14.5). Undue
tension clearly plays a role in widened and hypertrophic
scars. Wound tension causes edge separation and scar widen­
ing with time. Wound edges that are sharply defined and
aligned without tension heal with the least amount of scar­
ring. This is accomplished by approximating tissue with deep
buried subdermal stitches to minimize tension of overlying
tissue before final apposition. Additionally, the Gillies near-
far pulley can be used to aid approximation of higher tension
tissue. Skin eversion can be seen as an exaggerated applica­
tion of the principle of tension-free closure and can be accom­
plished with horizontal mattress and “flask-shaped” simple
sutures. However, care must be taken not to strangulate tissue
with overly tight stitches.
To prevent Burow’s triangles (“dog ears”), sutures should
be placed at the wound periphery so that redundancy can be
worked towards the middle, allowing for cleaner alignment
along the epidermis of the two wound edges during apposi­
tion. When tissues of differing thicknesses are closed, care
should be taken to capture a deeper bite of the thinner tissue
and a more superficial bite of the thicker tissue for proper
alignment. Likewise, when tissues are at differing heights,
taking a deeper bite of the lower tissue can help bring that
tissue level.
BOX 14.2  Surgical technique
Atraumatic technique
Minimizing tension
Skin eversion
Perfect apposition
Use of natural skin tension

203
Prevention
Fig. 14.5  (A–E) Skin eversion technique. Application of
deep stitches approximates the dermis and relieves
tension on the epidermis, contributing to less scar
widening.
A
B
C
D
E

204
CHAPTER 14 • Scar prevention, treatment, and revision
Fig. 14.6  Langer’s lines.
Fig. 14.7  Tension off-loading dressing.
Mechanical
off-loading
Decreased
scarring
Taping and coaptive films have also been used as adjunc­
tive therapy to prevent abnormal scarring.39,40 Silicone gel
sheeting, discussed in more detail later, has been considered
first-line prophylaxis although evidence is weak. Treatment
begins shortly after wound epithelialization, is worn 12–24
hours per day and continued for at least 1 month. Breast and
abdominal binders work as external splints to decrease skin
tension further. As with internal sutures, care should be taken
not to constrict adequate blood flow to the wound edge.
Current recommendations encourage the prophylactic use of
these measures in patients who have wounds in high-risk
areas such as the breast and thorax, or who have previously
developed abnormal scarring.41
Studies of over-the-counter remedies such as vitamin E
and onion extract have failed to provide good evidence in
support of their use.42–44 These studies have been criticized,
however, for their small sample size.45 Modalities such as
massage, hydrotherapy, and ultrasound also need additional
investigation before their role in treatment of scars can be
determined.
Lastly camouflage techniques can be a useful adjunct in
addressing the psychosocial dimension of scar management.
These strategies can be incorporated as a nurse-led aspect
of a practice and may positively affect patient quality of
life.46,47 A new spray-on, computer color-matched camouflage,
Microskin, has been shown to improve psychosocial measures
in pediatric burn patients.48 The product is purported to be
water- and sweat-proof, requiring reapplication every 4 to 5
days.
Treatment
Plastic surgeons today must apply surgical, nonsurgical, and
multimodal strategies in treating disfiguring and pathologic
scars. Treatment should be guided by diagnoses. Proper
diagnosis requires addressing the patient’s complaint, assess­
ing the characteristics of the scar, and understanding the state
of the scar with respect to scar biology. For instance, the
approach to a 17-year-old male emotionally burdened by
mature acne scars involving multiple facial subunits may
require a combination of counseling and nonsurgical modali­
ties. Alternatively, the functional impairment experienced by
a 45-year-old woman with hypertrophic scar limiting elbow
range of motion may require more invasive intervention. In
general, noninvasive strategies as described below offer a
good starting point in the treatment algorithm.

205
Treatment
years. Though the mechanism of action is unknown, one
hypothesis suggests that laser absorption by hemoglobin
results in capillary ablation and reduced perfusion. The heat
generated may also cause dissociation of disulfide bonds with
collagen fiber realignment.66 However, definitive conclusions
have been hampered by small sample size, short-term
follow-up, and lack of adequate controls. Review of the der­
matologic literature suggests some efficacy when lasers are
used as a monotherapy, especially in symptomatic relief of
pruritic and erythematous lesions.67 While ablative CO2 and
argon lasers have fallen out of favor in treating proliferative
scars due to high recurrence rates, newer high-energy pulsed
CO2 and Er:YAG lasers are under investigation and show
promise in the treatment of atrophic scars.68 Larger-scale
studies with long-term results are needed to further delineate
the role of laser therapy in scar management.
Topical treatments for hypertrophic scars offer the advan­
tage of convenience. Unfortunately, an effective topical
therapy has not yet been developed. Over-the-counter reme­
dies, including vitamin A, vitamin E, and onion extract, have
failed to show conclusive evidence in treating or preventing
hypertrophic scarring. A prescription topical immunomodu­
lator, imiquimod 5%, has also been investigated for scar
treatment and prevention. While early results suggested
improved cosmesis in postsurgical scars, subsequent studies
have failed to reproduce these effects.69,70 Skin-lightening
agents containing hydroquinone or retinol can aid in the treat­
ment of hyperpigmented scars.71 However their use is associ­
ated with significant side effects. For instance, in 2006 concern
over the carcinogenic risk of hydroquinone prompted a ban
of over-the-counter preparations over 2% in the US and a
comprehensive ban in Europe.
Treatment of keloid scar
There exists no uniformly successful treatment for keloid
scars. Therefore it is essential to discuss the risk of recurrence
with potential patients prior to embarking on therapy. Never­
theless, patients frequently seek treatment due to the disfigur­
ing physical and psychological burden of keloid scars.
Additionally, symptoms of pain and burning are commonly
associated with these scars. In such cases, best practice guide­
lines currently emphasize the importance of multimodal
therapy. Even so, appropriate goals must be set and the patient
must be made aware that lesions can redevelop or even
worsen on recurrence. Currently the only two viable treat­
ment options for mature keloids are to either (a) monitor the
scars routinely, or (b) to excise them and administer adjuvant
therapy. Excision and primary closure alone invariably results
in recurrence.
Adjuvant therapies for keloids include steroid injection,
radiation, cryotherapy, laser, and antitumor or immuno­
suppressive agents. In general, the first line adjuvant is
intralesional corticosteroid injections. Steroids have also
demonstrated synergistic benefits when utilized with other
modalities such as laser, radiotherapy, and cryotherapy. Tri­
amcinolone acetonide at 10 mg/mL is generally tried initially,
and if no response occurs, a 40 mg/mL concentration is
attempted. Injection into the dense scar is often painful and
associated with risk of infiltration into the surrounding normal
tissue. Early, rapidly proliferating lesions respond best to
steroid injections whereas slowly growing, mature keloids
Treatment of hypertrophic scar
Treatment options for hypertrophic scars include the applica­
tion of pressure garments, silicone sheets, corticosteroids,
laser therapy, and re-excision with primary closure. Primary
closure is most useful in cases of excess scarring caused by
infection or dehiscence. If the original wound was closed
following the basic tenets described above, then re-excision
with primary closure is not likely to result in an improved
scar compared to the initial procedure. Recurrence of hyper­
trophic scarring is quite high in these circumstances. Most
surgeons, therefore, do not treat hypertrophic scars with exci­
sion and primary closure unless adjuvant therapy is also
planned.
Silicone gel sheeting can both prevent hypertrophic scar
formation and accelerate its involution. Though a 2006
Cochrane review found only weak evidence to support sili­
cone sheeting, multiple randomized control trials (RCTs) have
since reconfirmed its value.49 Silicone gel sheeting has dem­
onstrated the ability to dramatically hasten hypertrophic scar
maturation and decrease associated symptoms of pain, rigid­
ity, and pruritus.50,51 However, silicone-containing oils and
creams have also exhibited mixed efficacy and silicone’s
mechanism of action in treating hypertrophic scars is still
under debate.52 One line of evidence points to increased
hydration from occlusion with subsequent decrease in inflam­
matory cytokines.53,54 Alternative suggested mechanisms
include a direct effect by silicone particles and an increase in
static electrical fields.55,56 Studies of related polyurethane-
and glycerin-based occlusive dressings are mixed, with some
studies demonstrating effectiveness equal to silicone.57,58
Since adoption in the 1970s, the use of compression gar­
ments has been a mainstay of burn scar management. Evidence
in the literature, however, has been less clear-cut. A prospec­
tive RCT of 122 burn patients by Chang et al. failed to show
significant improvement in time to scar maturation.59 Con­
versely a subsequent, more precise RCT in 2005 by Van den
Kerckhove et al. using both subjective and objective measures
found improved scar thickness when garment pressure was
above 15 mmHg.60 Yet another study, a 2009 meta-analysis of
six RCTs, including those mentioned above, found only mar­
ginal improvements of questionable clinical significance in
scar thickness.61 To date various clinical studies are ongoing
and the utility of compression garments in treating hypertro­
phic scars remain under debate.
Intralesional corticosteroid injections offer a second line of
therapy for hypertrophic scars refractory to silicone gel sheet­
ing. The exact mechanism is also unknown but likely reflects
focal suppression of inflammatory cytokines and inhibition of
fibroblast proliferation.62 Despite widespread consensus on its
efficacy, few studies have objectively evaluated intralesional
steroid treatment. The few studies that do exist suggest
response rates well over 50%. However, these studies are
limited by small sample sizes and unclear evaluation crite­
ria.63,64 In one such study, multimodality therapy combining
steroid injections with surgery improved response rates to
95% with no recurrence of scarring.65 However local side
effects from steroid injection include pain, skin atrophy,
telangiectasias, and dyspigmentation, demanding careful
application.
Pulsed-dye laser and other wavelength-specific lasers have
been used effectively to treat hypertrophic scars for many

206
CHAPTER 14 • Scar prevention, treatment, and revision
5-fluorouracil (5-FU), and bleomycin allow us to exploit our
growing understanding of scar biology to offer new solutions
to age-old problems. While the body of data is still small, early
evidence suggests that these drugs have potential for the safe
and effective treatment of excessive scarring.
TGF-βs are profibrotic growth factors that attract and
stimulate fibroblasts to increase collagen synthesis and
decrease ECM breakdown. Changes in TGF-β activity have
been linked to fibrotic diseases of the kidney, lung, and heart.
A robust body of literature implicates the TGF-β family as a
major determinant of scar morphology.84,85 This increased
knowledge of signaling pathways and TGF-β isomers has
been translated into new therapeutic avenues for exploration.
For instance, initial phase I/II trials of prophylactically
injected recombinant TGF-β3 have demonstrated an improve­
ment in the appearance of scars.86
IFNs are anti-fibrotic cytokines that suppress the formation
of collagen.87 Trials of intralesional injections of IFN-α2b and
later IFN-γ as both monotherapy and postsurgical adjuvant
therapy have yielded positive results. An early study found
reduced keloid recurrence rates of 18.7% with adjuvant IFN-
α2b injection versus 51.2% with surgery alone at a 7 month
follow-up.88 Subsequent studies, however, have been mixed.
Some trials have shown early recurrence when interferons
are used as monotherapy while others indicate benefits
with combined therapy.89,90 Nevertheless, targeted therapy
with IFN continues to be alluring from a biochemical stand­
point, and deserves further investigation.
Antineoplastic agents 5-FU and bleomycin are additional
promising pharmacologic candidates for treatment of patho­
logic scarring. Small RCTs have built upon the experience of
large clinical series to provide preliminary evidence for the
efficacy of 5-FU in keloid treatment.91–93 In one study, side-by-
side application of 5-FU and steroid injections on median
sternotomy keloids suggested equal efficacy for 5-FU without
the side effects of skin atrophy, hypopigmentation, or telangi­
ectasia seen with steroid treatment.94 Though not yet fully
understood, the effects of 5-FU may be mediated in part
through interference with the TGF-β signaling pathway.95
Bleomycin, on the other hand, is thought to act by binding
DNA and preventing mitosis.96 Initial clinical studies from
Europe suggest efficacy without systemic toxicity.97,98 While
results have thus far been favorable for both these agents,
larger-scale studies are needed to validate the findings of
early small studies.
Scar revision
Introduction
Plastic surgery education and techniques enable practitioners
to offer surgical, nonsurgical, and combined treatment modali­
ties to patients with scars. Treatment is therefore based on
understanding of underlying pathology rather than limited
to a certain tool or device. For the most disfiguring and
debilitating scars, surgery is often a necessary component of
therapy, if not the only effective therapy. After careful analysis
of a scar’s characteristics (morphology, maturity, distortion of
tissues) and appropriate application of noninvasive measures,
respond poorly. Intraoperative and postoperative intralesional
steroid therapy following excision has been shown to reduce
recurrence rates to below 50%.64,72
A short course of low-dose (20 Gy) radiotherapy to the
keloid excision wound immediately after excision has been
shown in numerous retrospective studies to reduce the rate of
recurrence.73–75 A more recent prospective study, however,
found recurrence rates of 72% at 1 year following excision and
radiotherapy.76 The immediate and long-term risks of radia­
tion therapy, including the potential for malignant transfor­
mation, demand further study. Nonetheless, radiation therapy
may reasonably be considered in adults with lesions refrac­
tory to other modalities.
Cryotherapy is a low-cost and effective method of treating
select keloid scars. In multiple retrospective series, complete
flattening or greater than 80% volume reduction occurred in
73–85% of lesions treated with liquid nitrogen.77–79 Early
lesions of less than 1–2 years’ duration appeared to have more
favorable results. A subsequent prospective study examining
cryotherapy of both hypertrophic and keloid scars found an
even greater response with hypertrophic scars.80 In this study,
a good to excellent response was found in 78.9% of hypertro­
phic scars versus only 50.9% of keloids. Interpretation,
however, is limited by vague evaluative criteria. Though the
mechanism is unknown, the effects of cryotherapy appear to
be synergistic with steroid injection.81,82 Yet despite its poten­
tial efficacy, cryotherapy has been limited to treatment of
small lesions due to adverse side effects such as pain, blister­
ing, lengthy wound healing, skin atrophy, and near-universal
dyspigmentation.
As with other modalities in scar treatment, critical evalua­
tion of lasers in keloid treatment has been complicated by
small studies with vague diagnostic criteria, inconsistent
evaluation and lack of long-term follow-up. Additionally, the
multitude of laser types and treatment algorithms complicates
direct comparative study. A 1995 study in The Lancet, for
instance, found decreased pruritus and scar height with
pulsed-dye laser treatment but did not distinguish keloid
from hypertrophic scar and had follow-up limited to 6
months.83 Though lasers have been utilized clinically for scar
treatment for nearly 20 years, prudent use is best advised
pending further study. Our experience has been favorable
when combining pulsed-dye laser with intralesional steroid
injection for keloids.
In summary, while there is yet no single modality
completely effective in keloid management, multimodality
approaches offer some promise. Current treatment algorithms
promote the use of corticosteroids, silicone sheeting, and
compression garments as first-line therapy, especially in small,
early keloids.38 Large, recalcitrant keloids can carry significant
morbidity and are very challenging to treat. Optimal manage­
ment may include surgery, steroids, radiation, or other
modalities and are best performed by a surgeon or center with
a focus on keloid treatment.
Emerging treatments
A promising new therapeutic modality is the local delivery of
antitumor and immunomodulatory drugs for the treatment of
keloid and hypertrophic scars. The use of immunomodula­
tory agents such as TGF-β modulators, interferons (IFNs),

207
Scar revision
entire scar, surgery should be deferred until scar maturity is
achieved. This can often take longer than with normotrophic
scars and should again be dictated by clinical exam. Dr. Mil­
lard’s principle “When in doubt, don’t!” bears stressing.1
Planning
In addition to timing, several other factors are important to
consider when planning for surgical scar revision. For complex
reconstructions involving multiple areas, management is best
directed at larger areas initially. For instance, burn scars
involving the head and neck should start with resurfacing of
the cervicofacial region before addressing the ectropion.
Surgeons must also determine if each scar is best treated
by single or multistaged revision. Single-staged operations
include both simple direct excisions and more complex soft-
tissue rearrangements. Unless an initial wound was widened
due to infection and dehiscence, direct excision alone is rarely
effective. When applicable, however, preoperative suturing
and on-table tissue expansion can be used to decrease tension
on a wound after direct excision. Undermining and advance­
ment of skin edges similarly allow for reapproximation
without tension. This can be performed asymmetrically to
change the degree of tension and deformity in neighboring
tissue. Subsequent use of a tension off-loading dressing can
further minimize scarring.37
Serial excision and tissue expansion are staged strategies
for scar revision. While seemingly simplistic, staged serial
excisions of scars may provide the best results (Fig. 14.8).
Two or three serial excisions of a large scar may accomplish
what is hazardous or even impossible in a single stage opera­
tion. Serial excision is accomplished by circumferentially
excising the margin of a scar, then undermining and advanc­
ing bordering normal tissue. The pliability of the normal
tissue should be assessed before making the incision. This
will dictate how much scar is safe to excise and timing of
subsequent stages.
Tissue expansion is an alternative method for staged scar
revision. This procedure enables the body to grow extra skin
for use in reconstruction through the placement of expanders
under the skin. Tissue expansion has been especially valuable
in scalp reconstruction of patients with burn alopecia, though
it does carry the additional risk of infection associated with
implant placement and requires two procedures for insertion
and subsequent removal.
Scar release
Scarring is a three-dimensional process that often extends
from superficial to deep tissue. Scar contracture in deep layers
can result in puckering and tethering of the overlying tissue.
This can occur even in the absence of superficial injury. Fat
necrosis following blunt tissue trauma, for instance, can result
in a concave skin defect without laceration. Treatment of
tethered scar requires release from the underlying tissue and
sometimes interposition of muscle or fascia. Soft-tissue fillers,
fat autograft, and acellular dermis have all been used success­
fully to fill depressed scars, although long-term data are
lacking.99–101
Acne scarring requires special consideration as the multiple
pitted scars of “ice-pick” acne can be disfiguring and result in
the plastic surgeon can then turn to an array of surgical tools
to treat a difficult scar.
Indications
Patients seek scar revision for a multitude of reasons. As
discussed earlier, scars carry both physical and psychologic
implications. Understanding what role these factors play in a
patient’s desire for treatment is important in setting and
reaching patient expectations.
Scars eliciting physical symptoms should be examined
carefully. Patients will often report discomfort and tightness
as a result of scar contraction. An exquisitely painful scar
should be examined for Tinel’s sign, which may suggest
entrapment of a cutaneous nerve. Excision or repair of a
neuroma is often an important part of scar revision. Scar
contractures across joints, frequently seen in burn patients,
can result in limited functionality and reduced range of
motion. In such cases, treatment should be directed at restora­
tion of function and be carried out in conjunction with aggres­
sive physical therapy to prevent recurrence.
Disfiguring scars can cause significant personal and social
burdens. The surgeon should be sympathetic and nonjudg­
mental as these scars may be reminders of past trauma and
current hardship. Administering care alongside a mental
health professional can help distinguish and address compli­
cating psychological issues. For the surgeon, extra care must
be taken in these circumstances to confirm realistic expecta­
tions and reinforce the goals of care.
Timing
Timing of scar revision should reflect an assessment of scar
maturity and an understanding of the underlying biology. A
soft supple mature scar is the ideal starting point from which
to consider revision. Immature scars contain the fragile blood
vessels of neovascularization, which may bleed excessively
during surgery. In addition, the tissue in and around imma­
ture scars is more edematous and less mobile, complicating
local tissue rearrangement. Tissue primed for scar revision
should be maximally mobile and soft.
Surgical timing should therefore be based on clinical
exam, though some suggest delay for at least 18 months.
Interval exams should be used to monitor a scar until one
can be certain of maturity. Any uncertainty in scar maturity
should prompt the physician to wait longer. This can often
be difficult in patients who are eager for a solution. Nonop­
erative management such as massage and silicone sheeting
should be offered to the patient during this period as it can
help maximize outcome. A patient’s compliance with nonop­
erative measures can also help serve as a measure of his or
her motivations and expectations. This can also be a time to
build a relationship of trust between the patient and physi­
cian. Those eager to proceed may not have realistic expecta­
tions and should be counseled accordingly. Patients should
be advised that early revision will increase the risk of com­
plications and will reset the clock on wound healing and
scar maturity.
Hypertrophic scarring can be thought of as a chronic
inflammatory condition. Early surgery is all the more plagued
by immobility and bleeding. Unless planning to excise the

208
CHAPTER 14 • Scar prevention, treatment, and revision
Fig. 14.8  (A–C) Serial excision.
A
B
C
considerable psychological stress for the patient. Mild to
moderate acne scars may benefit from resurfacing procedures
such as those using CO2 laser or chemical peels to even out
contour deformities.102 More serious acne scars, however,
require formal excision to achieve adequate depth. Focal exci­
sion with release of tethered tissue can be extremely effective
but should first be applied to one or two test lesions to assess
patient-specific results.
Principles of tissue rearrangement
The surgical approach to scar revision should be guided by
the same principles outlined for scar prevention. These include
atraumatic technique, tensionless closure, and proper skin
eversion. Scar revision that involves tissue rearrangement,
discussed further below, also requires consideration of ana­
tomic landmarks and lines of tension. Restoration of anatomic
landmarks such as the vermillion border, eyelid position, or
alar base should take priority over minimizing scar character­
istics.1 The use of local flaps in the face to prevent distortion
of anatomic landmarks is an example of this principle. In this
instance, the larger scar of a flap is preferred when local tissue
recruitment would result in deformity of facial landmarks.
Scar revision should similarly focus on restoring anatomic
structures to their correct location.
Scars should be hidden in the resting lines of skin tension.
Presented originally in 1861, Karl Langer’s eponymous “lines”
resulted from examination of vertical wounds left by circular
stab marks into a cadaver.103 Reorientation of a scar to these
lines allows for the least tension across a wound.104 This is
achieved in scar revision surgery via tissue rearrangement
techniques such as Z-plasty. The lines of resting tension form
the basis for the aesthetic units and subunits that dictate facial
surgery.104,105 The face, however, is dynamic and patients
should be cautioned that scars may become more apparent
with changes in expression.
Scar elongation and irregularization are other principles
that reflect consideration of tension lines caused by the scars
themselves. Myofibroblasts in a mature scar can cause scar
contracture within the axis of the scar. A long, straight scar
will result in uniform contracture in one axis, causing greater
deformity in the surrounding tissue and greater depression of
the scar. This tight scar can lead to limitations in movement.
Furthermore, the change in contour may be aesthetically
displeasing. Thus, in addition to reorienting the scar, local
tissue rearrangement techniques break up the length of the
original scar by incorporating neighboring tissue. A longer
scar relaxes the pull on each end of the scar towards the
center of the scar. Contractile forces are displaced into the
axis perpendicular to the length of the scar. Multiple applica­
tions of this technique result in an irregular scar, wherein
contractile forces are dispersed into multiple axes. This, in
turn, results in less tissue deformation and a more easily
camouflaged scar.
Scar revision techniques
Local tissue rearrangement requires an understanding of
tissue properties, careful planning, and meticulous technique.
When applied successfully, these simple but fundamental
principles embody the art of plastic surgery and enable the
surgeon to attain goals of scar reorientation, elongation, and
irregularization necessary for effectively addressing difficult
scars.
Though some argument exists, the Z-plasty technique can
be traced back at least as far as Horner in 1837 and Denonvil­
liers in 1854.106 Their procedure for transposing triangular
flaps to relieve cicatricial ectropion has evolved over time into
the modern Z-plasty. In current nomenclature, Z-plasty refers
to transposition of two triangular flaps, usually of equal size
and equal angle, into each other’s defect.
Planning and performing Z-plasty requires an understand­
ing of geometric principles. The first published mathematical
analysis came from Limberg in 1929.107 Through the Pythago­
rean theorem he revealed the theoretical gains in length
achievable with changes in the angle of the lateral limbs

209
Scar revision
Table 14.4  Z-plasty gains in length
Angle of lateral limb
of Z-plasty
Theoretical gain in length
of central limb (%)
30
25
45
50
60
75
75
100
90
120
BOX 14.3  The four fundamental functions of Z-plasty
1. To lengthen a scar
2. To break up a straight line
3. To move tissues from one area to another
4. To obliterate or create a web or cleft
60°
75% gain
in length
Tension
C
A
B
Fig. 14.9  (A–C) Simple Z-plasty.
(Table 14.4).108 In practical application, however, the elasticity
of skin and rigidity of scar create unequal deformation of the
central and lateral limbs.109 This deformation results in lower
gains in length in vivo than would be expected in theory.
Deformational forces are magnified with smaller flaps and
with serial Z-plasties. Nevertheless, proper execution of a
Z-plasty is essential to accomplishing four fundamental func­
tions: lengthening a scar, breaking up a line, moving tissue,
and obliterating or creating a web or cleft (Box 14.3).110
Z-plasties have been further divided into simple, planimet­
ric, skew, and multiple. The simple or stereometric Z-plasty
has two flaps of equal angle and length (Fig. 14.9). Tradition­
ally, these flaps are raised at 60° as this angle offers the best
balance between elongation in the axis of the scar and the
creation of tension forces pulling perpendicular to the scar.
Last-minute flap revisions can be avoided by incising and
transposing one flap to determine excursion accurately in vivo
before cutting the second flap.
The planimetric Z-plasty is a variation of the classic Z-plasty
that maintains the flaps in the same plane (Fig. 14.10).111 By
minimizing the amount of rotation and excising redundant
tissue, this flap design avoids the contours and depressions
created by simple Z-plasty. Flaps may theoretically be
designed with lateral limb angles ranging from 60° to 90°,
though most often they are planned at 75° angles. The plani­
metric Z-plasty is ideal for scar releases on flat surfaces where
lengthening is the primary objective and contour deformities
would be suboptimal.
Skew Z-plasties have lateral limbs departing at different
angles from one another (Fig. 14.11). This flap has been sug­
gested when anatomic landmarks mandate asymmetric move­
ment of one flap. Furnas and Fischer’s topographic study in
dogs revealed that the narrow flap transposed easily but was
likely to form a “dog ear”, while the wider flap was difficult
to transpose and caused more stretch at its base.109 This is
counterintuitive to some degree as the narrow flap has to
travel through a larger arc of rotation to traverse the wide flap.
For this reason, deformational forces created by skew Z-plasty
flaps can be difficult to predict and its use should be avoided.

210
CHAPTER 14 • Scar prevention, treatment, and revision
Fig. 14.10  Planimetric Z-plasty.
4
Tension
2
2
4
1
75°
Multiple-flap Z-plasty refers to multiple Z-plasties along
a scar length as well as Z-plasties designed with more than
two flaps (Fig. 14.12). When performing multiple Z-plasties
in series, the previous Z-plasty exerts deformational forces
on the tissue of the next Z-plasty, further limiting the actual
gain in length. A single large Z-plasty at a specific angle will
therefore create more length than multiple small Z-plasties
at that same angle. A large Z-plasty, however, is not always
in keeping with the aesthetic and functional goals of a
scar revision. Numerous Z-plasties utilizing multiple flaps
have been devised. Among them, the Limberg’s four-flap
and Mustarde’s “jumping man” five-flap Z-plasties are
frequently used for release of first-webspace contractures
(Fig. 14.13).107,112
Regardless of design, care must be taken to widen the tip
of flaps to avoid tip necrosis.113 The thickness of flaps is
Fig. 14.11  Skew Z-plasty. (Reproduced from Furnas
DW. Transposition of the screw z-plasty. Br J Plast Surg.
1966;19:88–89.)
dictated by the quality and location of the tissue. Scars often
have distorted and unreliable blood supply, therefore thicker
flaps are necessary. In unscarred tissue, care must be taken to
elevate the subdermal vascular plexus to include the cutane­
ous microvasculature in the flap.
Other scar revision techniques include V–Y and Y–V
advancement flaps, W-plasty and geometric broken line. V–Y
and Y–V advancement flaps allow for the incorporation of
adjacent tissue without the threat to vasculature necessary
for Z-plasty (Fig. 14.14). These flaps are not transposed
and therefore do not require undermining. Like Z-plasties,
these flaps can be carried out in tandem through careful
flap design.
W-plasty and geometric broken line are techniques for scar
irregularization (Figs. 14.15, 14.16).114 W-plasty uses a zigzag
pattern excision of the scar followed by reapproximation of

211
Scar revision
Fig. 14.13  Four-flap Z-plasty.
A
B
C
D
A
A
B
B
C
C
D
D
60°
60°
60°
60°
A
B
Fig. 14.12  (A–C) Multiple Z-plasties. (With permission from Dr. Shelly Noland.)
C

212
CHAPTER 14 • Scar prevention, treatment, and revision
Scar
Fig. 14.14  V–Y and Y–V advancement flaps.
RSTL
Fig. 14.15  W-plasty. RSTL, relaxed skin tension lines.
Fig. 14.16  Geometric broken line.
small interdigitated limbs. There is no elongation of the scar
and tissue is removed, therefore a net increase in tension is
produced in the axis perpendicular to the scar. In contrast,
Z-plasty trades relaxation in the axis of scar for tension
perpendicular to the scar, resulting in no change in overall
tension. Albert F. Borges has suggested W-plasty as a good
revision technique in facial scars that are not in the resting
lines of skin tension and do not have excessive tension
across them.114
Lastly, geometric broken line is a refined technique wherein
5–6 mm randomly distributed triangles, squares, trapezoids,
and semicircles are incised at the wound edge with reciprocat­
ing shapes planned opposite them. However, this technique
is challenging and labor-intensive, though it may have some
utility in further camouflaging facial scars that cross aesthetic
subunits.
Postoperative care and follow-up
Initial postoperative care should be directed towards optimal
wound healing, including adequate nutrition, blood sugar
control, smoking cessation, and activity precautions. Long-
term scar reduction techniques are aimed at prevention
and treatment. Following a revision, scar reduction can
be achieved through use of a tension off-loading device.
Aggressive use of taping, silicone sheeting, compression, and
scar massage may also provide modest improvement. More
detailed follow-up care should be dictated by patient-specific
factors. Regardless of complexity, however, both the patient
and physician benefit from long-term follow-up as this pro­
vides an opportunity to evaluate the efficacy of any treatment
strategies.

213
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94. Manuskiatti W, Fitzpatrick RE. Treatment response of keloidal and
hypertrophic sternotomy scars: comparison among intralesional
corticosteroid, 5-fluorouracil, and 585-nm flashlamp-pumped
pulsed-dye laser treatments. Arch Dermatol. 2002;138:1149–1155.
95. Wendling J, Marchand A, Mauviel A, et al. 5-fluorouracil blocks
transforming growth factor-beta-induced alpha 2 type I collagen
gene (COL1A2) expression in human fibroblasts via c-Jun
NH2-terminal kinase/activator protein-1 activation. Mol Pharmacol.
2003;64:707–713.
96. Bennett JM, Reich SD. Bleomycin. Ann Intern Med. 1979;90:945–948.
97. Shridharani SM, Magarakis M, Manson PN, et al. The emerging
role of antineoplastic agents in the treatment of keloids and
hypertrophic scars: a review. Ann Plast Surg. 2010;64:355–361.
98. Espana A, Solano T, Quintanilla E. Bleomycin in the treatment of
keloids and hypertrophic scars by multiple needle punctures.
Dermatol Surg. 2001;27:23–27.
99. de Benito J, Fernandez I, Nanda V. Treatment of depressed scars
with a dissecting cannula and an autologous fat graft. Aesthetic
Plast Surg. 1999;23:367–370.
100. Kasper DA, Cohen JL, Saxena A, et al. Fillers for postsurgical
depressed scars after skin cancer reconstruction. J Drugs Dermatol.
2008;7:486–487.
101. Ramos Duron LE, Martinez Pardo ME, Olivera Zavaleta V, et al.
Application of acellular dermis and autograft on burns and scars.
Ann Transplant. 1999;4:74–77.
102. Shamban AT, Narurkar VA. Multimodal treatment of acne, acne
scars and pigmentation. Dermatol Clin. 2009;27:459–471, vi.
103. On the anatomy and physiology of the skin. I. The cleavability of
the cutis. (Translated from Langer, K. (1861). Zur Anatomie und
Physiologie der Haut. I. Uber die Spaltbarkeit der Cutis.
Sitzungsbericht der Mathematisch-naturwissenschaftlichen Classe
der Kaiserlichen Academie der Wissenschaften, 44, 19.). Br J Plast
Surg. 1978;31:3–8.
104. Borges AF. Relaxed skin tension lines (RSTL) versus other skin
lines. Plast Reconstr Surg. 1984;73:144–150. Cuban-born plastic
surgeon Alberto F. Borges (1919–1990) extolled the importance of
reorienting wounds to the relaxed lines of skin tension. Though himself a
master craftsman, his work in examining the principles of scar revision
beyond simple technique places him among historic artisans who have
helped translate craft into science.
105. Burget GC, Menick FJ. The subunit principle in nasal
reconstruction. Plast Reconstr Surg. 1985;76:239–247.
106. Borges AF, Gibson T. The original Z-plasty. Br J Plast Surg.
1973;26:237–246.
107. Limberg AA. Skin plastic with shifting triangle flaps. In: Collection
of Scientific Works in Memory of 50th Anniversary of the Medial
Postgraduate Institute. Leningrad: Traumatological Institute;
1929:862.
108. Rohrich RJ, Zbar RI. A simplified algorithm for the use of Z-plasty.
Plast Reconstr Surg. 1999;103:1513–1517; quiz 1518. Rohrich and
Zbar’s review of the history and technique of Z-plasty highlights key
points in flap design including flap thickness, angle, and location. Facile
application of Z-plasty is necessary for all plastic surgeons to master.
109. Furnas DW, Fischer GW. The Z-plasty: biomechanics and
mathematics. Br J Plast Surg. 1971;24:144–160.
110. Furnas DW. The four fundamental functions of the X-plasty. Arch
Surg. 1968;96:458–463.
111. Roggendorf E. The planimetric Z-plasty. Plast Reconstr Surg.
1983;71:834–842.
112. Mustarde JC. The treatment of ptosis and epicanthal folds. Br J
Plast Surg. 1959;12:252–258.
113. Davis JS, Kitlowski EA. The theory and practical use of the
z-incision for the relief of scar contractures. Ann Surg.
1939;109:1001–1015.
114. Borges AF. W-plasty. Ann Plast Surg. 1979;3:153–159.

15 
Skin graft
Saja S. Scherer-Pietramaggiori, Giorgio Pietramaggiori, and Dennis P. Orgill
SYNOPSIS
■ History of skin grafting mirrors many of the important advances of
plastic surgery.
■ There are complex biologic mechanisms that allow skin grafts to take.
■ There are a variety of types of skin grafts that can be selected based
on clinical application.
■ Technique should be adjusted to avoid most complications.
■ There are exciting areas of research that will help minimize donor site
size and improve function and appearance of skin grafts.
Skin grafting is a technique for the transfer of cutaneous tissue
from one site of the body to another, often to cover large
defects. Depending on the thickness of the dermis of graft that
is harvested, skin grafts are defined as full-thickness or split-
thickness. See Fig. 15.1, Box 15.1 and Video 15.1
for a
step-by-step guide on how to prepare a skin graft.
Access the Historical Perspective section online at

Anatomy and physiology
The skin represents approximately 8% of our total body
weight, with a surface area of 1.2–2.2 m2. The skin is
0.5–4.0 mm thick and covers the entire external surface of the
body, including the walls of the external acoustic meatus and
the lateral tympanic membrane. The main function of skin is
to protect body contents from the environment, including
pathogens, temperature, and excessive water loss. Insulation,
temperature regulation, sensation, immune function, and the
synthesis of vitamin D are all critical functions of the skin.
Skin loses regenerative capacity when lesioned down to the
lower dermis and results in scar tissue when injured.
Epidermis
Skin has a complex three-dimensional structure characterized
by two overlapping layers, the epidermis and the dermis. The
epidermis, as the nervous system, derives after gastrulation
from the neuroectoderm. Epidermis is the outer or upper layer
of skin, which is a thin, semitransparent, water-impermeable
tissue, consisting primarily of keratinocytes. These cells form
a multilayered keratinized epithelium, similar to a wall of
bricks. The basement membrane separates the epidermis from
the dermal tissue and consists of a protein structure produced
by basal keratinocytes. Basal keratinocytes are partially dif­
ferentiated stem cells of the epidermis that provide the prolif­
erative and regenerative capacity of the skin epithelium. The
epithelium is metabolically active and continuously self-
renews to maintain an efficient barrier function. Cellular
homeostatic regulation is, as a consequence, very important:
too little proliferation would bring a loss of barrier and exces­
sive activity to hyperproliferative disorders, such as psoriasis.
Homeostasis is granted by the basal epidermal cells, which
periodically cycle, executing their program of terminal
differentiation, a process that takes approximately 28 days.
The differentiation of the keratinocytes is characterized by
the progressive production of alpha-keratin, with migration
towards the surface until the cells lose their intercellular con­
nections (desmosomes), die, and become corneal lamina.
During this process, called cornification, basal keratino­
cytes produce tonofilaments (precursor of keratin) and then
transform into the stratum spinosum as the desmosomes
stretch the cells into spikes visible with a microscope. In the
plasmalemma, the tonofilaments are connected to the desmo­
somes. Cells next start to produce keratohyalin, which aggre­
gates in dense and basophilic granules, giving the name to the
stratum granulosum. In these granules a histidine-rich protein,
profilaggrin, becomes progressively filaggrin, which ulti­
mately acts as a glue to keep keratin filaments together once
the cells die and the cell membrane degrades.
As the cells divide and move up through the epidermis
they eventually transform into the stratum corneum, a layer
  Access video and video lecture content for this chapter online at expertconsult.com

214.e1
Historical perspective
Historical perspective
Skin is the largest human organ, covering 1.7 m2 in the average
adult. It serves as an essential barrier with mechanical, immu­
nological, and aesthetic functions. Skin transplantation has
long fascinated humans and there is evidence that skin grafts
were performed in India as early as 1500 BC for traumatic
nasal amputation. Modern science has taught us much about
the anatomy and physiology of skin.
Gaspare Tagliacozzi, one of the first reconstructive surgeons
(1545–1599),1 described pedicled skin flaps from the arm for
nasal reconstruction in patients. Two centuries later research
was conducted by Giuseppe Baronio (1750–1811), who per­
formed and published for the first time skin grafts in a lamb
(Degli innesti animali, 1804).2 Jonathan Warren in Boston and
Joseph Pancoast in Philadelphia were among the first to
perform and describe autologous full-thickness skin grafting
in humans using the arm as a donor site. Paul Bert, a French
politician, showed in his thesis that skin graft survival is only
possible if blood vessels of the recipient site are able to revas­
cularize the graft. His work popularized this technique.3 For
the techniques, Reverdin, a French student, described harvest­
ing skin islands with the scalpel tip with transfer to a first web
space wound.4 He discovered that these skin islands not only
temporarily covered, but also actively stimulated, wound
healing. Reverdin’s work was rapidly accepted and performed
by multiple surgeons in the US. The term “dermoepidermoid”
graft was introduced by Leopold Ollier (1830–1900), who also
first used the split-thickness skin graft (STSG) to close entire
wounds.5 He noticed that healing was achieved faster and
wound contraction was minimized. The German surgeon Carl
Thiersch (1822–1895) further developed the technique of skin
grafting and introduced the concept of wound bed prepara­
tion by removing granulation tissue to achieve a clean wound
bed to facilitate graft revascularization. The English ophthal­
mologist, John Reissberg Wolfe (1824–1904), from Glasgow,
published the use of a full-thickness skin graft for ectropium
correction.
With the development of skin harvest techniques the
number of publications reporting clinical results of skin grafts
increased exponentially. Later, James Carlton Tanner (1921–
1996) revolutionized burn surgery by the introduction of
meshing to expand skin grafts in order to cover larger wounds
with minimal donor site morbidity.6
Reverdin’s technique was modified by John S Davis
(1872–1946), who elevated the skin with a needle in 1914 to
facilitate harvesting, a technique that he called “pinch graft”.4
In 1920 Ricardo Finochietto (1888–1962) developed a knife to
elevate larger skin areas manually by controlling the thickness
of the skin graft. Ten years later, the invention of the shave
blade by Humby further facilitated skin harvest.
The introduction of the mechanical dermatome of Padgett-
Hood and Reese in 1940 and 8 years later the development of
the electric dermatome by Harry Brown significantly facili­
tated skin harvest of large surfaces in a controlled manner.

215
Anatomy and physiology
A
B
C
Excision of
burn
Skin graft in mesher
Removal of
skin graft
Mesh
graft
Fig. 15.1  Excision and grafting. A combination of excision and
grafting is the preferred approach for the treatment of deep dermal
burns. The burn is excised (A) until a viable wound bed is reached,
as evidenced by capillary bleeding. The graft (B) is a thin layer of
skin, consisting of epidermis and partial-thickness dermis, which is
harvested from a nonaffected area, often the anterior thigh or
abdomen. The skin graft is placed over the excised area (C) and
attached with sutures or staples. Reduction of the size of skin-graft
donor sites can be accomplished by making the split-thickness skin
graft into a “mesh graft” by placing multiple small slits in the graft,
allowing it to expand by up to six times the original area. (Adapted
from Orgill DP. Excision and skin grafting of thermal burns. N Engl J
Med. 2009;360:893–901.)
• Prepare the wound bed for grafting (debridement and
hemostasis)
• Estimate the needed skin graft size
• Clean the donor site from any residual disinfection (i.e.
Betadine)
• Apply paraffin on the donor site
• Set the dermatome at 0.2 mm thickness
• Stretch the donor site skin
• Apply the dermatome at a 45° angle and apply light pressure
• Slide the dermatome along the skin while an assistant is lifting
the skin graft with two forceps
• Lift the dermatome upwards when the desired size of graft is
obtained
• Dress the donor site with Vaseline gauze, dry gauze and
bandages
• Fix the bandage generously to the skin (e.g. thigh) to avoid
sliding down of the dressing
• Spread evenly the graft (dermal site of the graft upwards) on a
dermal carrier (rough surface of the carrier upwards) of the
desired size (1 : 1.5, 1 : 3, etc).
• Pass the graft through the graft mesher paying attention that it
does not detach from the dermal carrier
• Apply the graft on the recipient site by sutures, surgical staples
or fibrin glue
• When indicated apply a bolster dressing by placing Vaseline
gauze on the skin graft, followed by a cotton sponge
impregnated with Betadine or saline solution and tight sutures
(4/0 nylon or polypropylene) from the opposite wound margins
together at the center of the defect
• First dressing change should be around 5–7 days post-op
BOX 15.1  How to perform a skin graft
of dead cells, which ultimately is highly mechanically and
chemically resistant due to chemical bonds between lipids
and proteins. It is thought that cells die as the increasing
proteins in their cytoplasm start to activate lysosomes. The
stratum corneum provides an extremely effective barrier layer
to keep water in and microorganisms out.
Also contained within the epidermis are melanocytes,
Langerhans cells, Merkel cells, and sensitive nerves. Around
10% of the epidermal cells are represented by melanocytes,
which derive from the neural crest. These complex dendritic
cells produce melanin granules (contained in the melano­
somes) that are then transported through dendrites into
keratinocytes, providing color to the skin and protecting basal
epithelial nuclei from ultraviolet damage. Melanocytes are
anchored to the basal lamina by hemidesmosomes, but do not
have desmosomic connections with other cells.

216
CHAPTER 15 • Skin graft
including the hair follicle bulb. Arterial capillaries generate
venous plexi, which have the same distribution of arterial
vasculature. In the deep layers of dermis it is possible to
find several arteriovenous anastomoses, particularly at the
extremities (hands, feet, ears), where they exhibit strong
muscular sphincters. The function of these structures is mainly
under the control of the visceral nervous system, with the
main function of thermoregulation and intravascular volume
redistribution.
Blind-ended lymphatic structures are present in the dermis
from where they connect to the reticular plexus and to
larger vessels in the subcutaneous tissue. In this region, lym­
phatic vessels are larger, with valves, and drain into deeper
lymphatic vessels called regional collectors. In the skin the
lymphatic drainage is very active with multiple interconnec­
tions enabling lymphatic exchange. Circumferential skin and
subcutaneous damage can therefore lead to problematic
lymphatic stasis in extremities or in the genital area.
Stem cells and regeneration of skin
Basal epithelial keratinocytes are the committed stem cells of
the epidermis. Constant self-renewal provides a new protec­
tive layer at the skin surface.7–12 Hair follicles contain multi­
potent stem cells that are activated upon the start of a new
hair cycle and upon wounding to provide cells for hair follicle
and epidermal regeneration. In the hair follicle, stem cells
reside in the bulge area. Bulge cells are relatively quiescent
compared with other cells within the follicle.9,10 However,
during the hair cycle, bulge cells are stimulated to exit
the stem cell niche, proliferate,13 and differentiate to form
the various cell types of the hair follicle.14 In addition, bulge
cells can be recruited during wound healing to support
re-epithelialization.15,16
The relative importance and exact contribution of bulge
cells to wound healing are currently unknown as areas of the
body such as the palms and soles that lack hair follicles still
exhibit normal healing.
Hair follicles
Hair differentiates in a craniocaudal direction, 9 weeks
after gestation, as mesenchymal cells populate the skin to
form the dermis. Specialized cells in the dermal layer stimu­
late epithelial cells to proliferate and migrate downward into
the epidermis, forming hair canals. The complete developed
hair follicle contains an ectoderm-derived matrix and an
underlying mesoderm-derived follicular papilla. There are
three bulges that attach to the hair bulb. At the base the erector
muscle develops, the middle part gives rise to the sebaceous
gland, and the superficial bulge develops into an apocrine
unit (Fig. 15.2).
Histological structures of the hair follicle can be divided as
follows. The part that reaches from the entrance of the hair
follicle into the skin to the apocrine gland is the infundibulum.
The zone between the apocrine gland and the sebaceous gland
is referred to as the isthmus. The stem of the hair follicle is
located between the sebaceous gland and the base of the
erector muscle. The bulb is the deepest part of the hair follicle
and contains the follicular matrix and papilla. This part is
growing and regenerates the hair after injury. If the bulb is
lesioned the hair will not recover from injury.
Langerhans cells are the immune cells of the epidermis and
are important in generating a response to foreign agents,
playing an important role in allograft rejection and contact
dermatitis. These cells are situated in the stratum spinosum
and, with long dendrites, slide between epithelial cells,
without desmosomic connections to them. Langerhans cells
share several features with macrophages of connective tissues.
Merkel cells are commonly found in the epidermis of
palms, soles, nail beds, oral and genital areas. Merkel cells act
as mechanoreceptors and thus are responsible for neurosen­
sory transmission. These cells reside in the basal layer of the
epidermis, often protruding into the dermal layer like nails.
Merkel cells are connected by desmosomes to the neighboring
cells.
Skin adnexal structures are epidermal derivatives that
invaginate into the dermis with a lining of epithelial cells.
They include hair follicles, sweat and sebaceous glands. These
structures provide the basis for re-epithelialization following
the harvest of a split-thickness skin graft (STSG).
Sensitive nerve supply to the skin is rich and extends
through the basement membrane into the epidermis. Nerve
fibers also go to skin adnexal organs that allow hair to become
erect and sweat glands to secrete.
Dermis
The dermis is a tough fibrous layer that provides the mechani­
cal features of the skin. It is composed primarily of collagens,
glycosaminoglycans, and elastins. Skin grafts without the
dermis result in a closed but often unstable skin. Grafting a
part of the dermis is therefore very important to consider in
terms of functionality of the future skin.
The upper part of the dermis has a particular architectural
organization that is called papillar and contains blood vessels
and nerve fibers. The papillar layer of dermis consists of fine
collagenous fibers that form an undulating interface with the
overlying basement membrane and epidermis. This structure
increases the contact area between dermis and epidermis,
allowing for maximal mechanical stability of the two layers
and an exchange surface for diffusion. Deeper, we find the
reticular dermis, with increasingly thicker collagenous fibers
(mainly of type I) as we move toward the subcutaneous tissue.
The reticular dermis has larger collagenous fibers with sub­
stantial strength. The mechanical properties of the dermis are
critical to allow movement while providing stability and
protection from mechanical trauma. The dermis is remarkably
self-healing, mainly due to the presence and activation of
myofibroblasts following injury.
Blood vessel supply of the skin
Dermal vascularization is particularly important, as blood
vessels are not directly present in the relatively more meta­
bolically active epidermal layer, glands, and hair follicles.
Blood vessels set up a rich superficial plexus just underneath
the basement membrane in the papillary dermis, facilitating
nutrient transport to the epidermis. The blood vessels in the
papillary dermis are arranged in the papillary plexus, with a
rich network of capillaries in the papillae, which come in close
contact with the epidermis. Deeper in the dermis is the reticu­
lar plexus from which small vessels distribute to the subcuta­
neous and deep dermal tissues to vascularize adnexal organs,

217
Science
Sweat glands are divided into eccrine and apocrine glands.
There are numerous eccrine glands in every region of the
body except the tympanic membranes, lips, nail bed, nipples
and clitoris. Their body has a glomerular structure and they
excrete a clear odorless, hypotonic liquid. The secretion is
stimulated mainly by an increase in body temperature, with
the exception of some regions, such as palms, face, and axilla,
where the main stimulus is emotional.
Apocrine glands are found exclusively in the axillar, peri­
anal, periumbilical, areolar, preputial, scrotal, pubic and
vulvar areas. While their structure is similar to that of the
eccrine glands, these glands differ as regards the quality of
their excretions, which are characterized by a thick milky,
protein-rich fluid, which has a striking odor after bacterial
colonization.
Science
Mechanisms of skin graft take
Skin grafting is the transfer of autologous skin cells left in
anatomic order but without an intact blood supply. Therefore
time and the recipient surrounding conditions limit the vital­
ity. The operative procedure allows for nearly immediate
Follicles can be found in different phases: anagen (prolifer­
ating phase), catagen (regression phase), and telogen (resting
phase).
Although no new hair follicles are made postnatally, the
lower portion of the hair follicle regenerates in order to
produce new hair. Some of this capacity has been linked to
the presence of multipotent epithelial stem cells. These cells
can be found in the lowest permanent portion of the hair
follicle – the bulge.13 Bulge stem cells are activated during the
transition from telogen to anagen, to restart hair growth.
Glandular structures
Sebaceous glands are small saccular structures residing
throughout the dermis, but are more common in thicker areas.
These glands produce lipid-rich sebum on the surface of the
skin and around the hair shaft. The function of sebum is
still partially unknown but probably is linked to protection
of the hair and contributes to the impermeabilization of the
skin, giving protection from stings and parasites. Sebaceous
glands are particularly large on the face, trunk, shoulders, and
genital and perianal regions. When excessive quantities of
sebum are produced – such as during puberty – the duct can
be obstructed and ultimately may become infected or form
cysts.
Fig. 15.2  Skin grafts. (A) Split-thickness skin grafts (STSGs) are the preferred approach for
the treatment of large superficial skin defects such as dermal burns. STSGs consist of the
partial-thickness dermis and the epidermis. Depending on the thickness, STSGs are referred to
as thin or thick STSGs. In thick STSGs superficial hair follicles can be included into the graft
and restore hair growth and functional sweat glands in the future skin. (B) Full-thickness skin
grafts are limited in availability and are used in the reconstruction of aesthetic (face) or
functional (hand) body areas. The graft is usually taken from behind the ear, or the inguinal or
elbow fold. The graft consists of the complete dermal and epidermal layer, including hair
follicles and glandular structures. (C) Hair follicle: histological structures of the hair follicle.
The presence of epidermal cells as far as the bulb explains the fast re-epithelialization after
STSG harvest at the donor site. The infundibulum reaches from the entrance of the hair follicle
into the skin to the apocrine gland. The zone between the apocrine gland and the sebaceous
gland is referred to as the isthmus. The stem of the hair follicle is located between the
sebaceous gland and the base of the erector muscle. The bulb is the deepest part of the hair
follicle and contains the follicular matrix and papilla. This part grows and regenerates the hair
after injury. If the bulb is lesioned the hair will not recover from injury. (Adapted from Orgill DP.
Excision and skin grafting of thermal burns. N Engl J Med. 2009;360:893–901.61)
A
Epidermis
Dermis
Sebaceous gland
Hair follicle
Fat
Sweat gland
B
C
Sebaceous gland
Bulge region
Outer root sheath
Inner root sheath
Hair fiber
Dermal papilla

218
CHAPTER 15 • Skin graft
inosculation,3,18,19,25 but the mechanism of revascularization
remained unclear for many years.
Three hypotheses of revascularization are supported by
the literature, each of them probably contributing to the
process: anastomosis, neovascularization, and endothelial cell
ingrowth. Anastomosis is the process of reconnection between
the blood vessels in the recipient site wound bed and the
graft.21,23,24,26–28 Neovascularization is characterized by new
vessel ingrowth from the recipient site into the skin graft. The
last mechanism describes endothelial cell proliferation and
sliding from the recipient site, utilizing pre-existing vascular
basal lamina as a structure, while in the graft endothelial cells
gradually degenerate.22,24,29–31
The process of revascularization begins as early as 24–48
hours after grafting.32,33 Many authors describe vessel ingrowth
mainly from the wound bed and less so from the wound
margins, since no significant increase in blood vessels was
seen in graft margins after skin grafting.21,24,32–35 Studies sup­
porting vessel ingrowth from the host as the main mechanism
of skin graft revascularization have been controversial with
respect to time course and the mechanism of host–graft vessel
interactions.23,36 Some early studies demonstrated by intrave­
nous injection with radioisotopes that blood flow in the graft
was established 4 days after grafting.37 Similarly, studies using
India ink showed graft vessel stain as early as 2 days post­
grafting.23 More recently, it was demonstrated, using a trans­
genic tie2/pacZ mouse model, that vessel ingrowth appears
in the periphery of the graft (following blood vessel regres­
sion in the graft) from day 3 until day 21.38 Zarem et al.22
suggested that the process of vascularization of full-thickness
skin grafts in the mouse is dominated by vascular ingrowth
from the recipient using a modified transparent skin chamber.
Henry and Friedman36 proposed the theory that endothelial
cells of superficial graft vessels degenerate and that host
vessels profit from the basement membrane-covered infra­
structure for new vessel ingrowth. In 1967, other investigators
confirmed this theory using the graft hamster cheek pouch
and showed a similar vessel pattern before and after graft­
ing.39 Converse and Ballantyne further investigated endothe­
lial cell ingrowth into the graft using diaphorase, a marker of
viable vascular endothelium. They found increased diapho­
rase levels in the graft bed 4 days after grafting, supporting
the theory of vascular ingrowth from the host. As very few
functional anastomoses were present, the authors concluded
that both mechanisms, inosculation and vascular ingrowth,
were important in the process of revascularization.31 Vessel
regression was also supported by NADH diaphorase activity
loss during the first 4 days after grafting that was probably
taken up by new vessel ingrowth.29,38,39 The conclusion that
endothelial cells utilize preformed tunnels of basal lamina
was triggered by the observation that initially empty graft
vessels subsequently became infiltrated with leukocytes and
that ingrowing vessels used the white blood cell-filled channel
as a conduit.22 Later studies showed a central refilling of the
graft vasculature as early as 48 hours, leading to the conclu­
sion that early anastomosis between host and graft vessels
may play a major role in graft revascularization, as vessel
growth occurs at about 5 µm/hour and angiogenesis would
take at least 5 days to reach the 600-µm-thick murine
dermis.22,40 In 1987 Demarchez et al.41 supported this hypoth­
esis by grafting athymic mice with human STSGs. Double
labeling of cross-reacting antifactor VIII and a human-specific
coverage of large wound areas. Meshed grafts allow further
expansion of skin but leave multiple small wounds that are
re-epithelialized, mainly from the mesh within a few days.
Skin can also be expanded through multiple small skin island
grafts (as in Reverdin’s technique) that stimulate granulation
tissue, probably by excreting growth factors. In STSGs, kera­
tinocytes on the basal layer show high proliferation rates,
which may ultimately stimulate growth factor excretion.17
Three phases of skin graft take are commonly described:
(1) serum imbibition; (2) revascularization; and (3) maturation
(Fig. 15.3).
Serum imbibition
In the first days, before the graft revascularizes, oxygen and
nutrients diffusing through the plasma between the graft and
the wound bed will nourish the skin graft. Huebscher in
188818 and Goldmann in 189419 theorized that skin grafts
might be nourished by host fluid before vascularization of the
graft occurs. They referred to this as “plasmatic circula­
tion.”18,19 Later, Converse et al.20 altered the term to “serum
imbibition”, as fibrinogen changes into fibrin that fixes the
skin graft on to the wound bed in the absence of real plasmatic
flow. Converse’s studies show that skin grafts gain up to 40%
of their initial weight within the first 24 hours after grafting
and then this gain is reduced to 5% at 1 week postgrafting.20
In the first hours, passive absorption of serum from the wound
bed causes edema, which resolves when the revascularization
is functional (see Fig. 15.3).
Revascularization
Revascularization is critical for long-term skin graft survival.
Early studies in the 19th century21–24 suggested a connection
between the wound bed and graft vessels, referred to as
Fig. 15.3  The concept of revascularization of the graft. Skin graft take is
characterized by three main phases: (1) Plasma imbibition: the graft is initially
nourished by the plasma circulation from the wound side. (2) Blood vessel
connection: three different theories of how the skin graft revascularizes on the
wound bed are described: (a) graft vessels regress and leave a basal lamina
infrastructure followed by ingrowth of host epithelial cell ingrowth; (b) the
reconnection of graft and host open ends; and (c) the ingrowth of endothelial cells
from the host into the graft. (3) Revascularization of the skin graft. (Adapted from
Capla JM, Ceradini DJ, Tepper OM, et al. Skin graft vascularization involves
precisely regulated regression and replacement of endothelial cells through both
angiogenesis and vasculogenesis. Plast Reconstr Surg. 2006;117: 836–844.)
1. Plasma imbibition
2. Blood vessel connection
3. Revascularization
Fibroblast
Basal lamina

219
Clinical application
Skin appendages and functional structures
Hair follicles, sweat glands, and dermal nerves can often be
transferred within thick STSGs and full-thickness skin grafts
(see Fig. 15.2). Thin STSGs will not allow the transfer of hair
or other adnexal glands, as the regenerating bulb is not har­
vested. Hair regrowth can occur in STSGs but, due to the
shallow depth of harvest, is rather unlikely. Full-thickness and
composite grafts will show hair regrowth 2–3 months after
grafting.
It is still unclear how nerves regrow into the skin graft.
Studies demonstrated that recipient nerves use the basal
lamina infrastructure of degenerated blood vessels and
Schwann cells of donor nerves to grow. Although histological
images reveal similar neural structures between healthy skin
and integrated skin grafts, patients report abnormal sensation,
including hypersensitivity and pain, up to 1 year after graft­
ing. Usually patients regain sensitivity of the grafted area after
1 year, but the result is not completely normal.
Neural reconnection to sweat glands will reactivate their
function up to 3 months after grafting. For this reason, mois­
turizing of the skin graft is advised for at least 3 months to
avoid dryness.
Full-thickness skin grafts include skin appendages that can
survive and be functional at the recipient side, while STSGs
do not contain the deep structure skin appendages and remain
without glandular function or hair growth.
Clinical application
Skin wounds that extend into the deep dermis heal through
the mechanisms of scarring and wound contraction. For large
antitype IV collagen antibody showed initial anastomosis
between graft and host vessels. Murine host cells gradually
replaced vascular structure and the extracellular matrix of the
skin graft. Later studies confirmed this hypothesis by observ­
ing a similar blood vessel network of the skin graft at the
donor site and after revascularization of the graft between 96
and 120 hours after grafting.32
Capla et al. further showed that about 20% of blood
vessels supporting the microcirculation on day 7 after
grafting occurred by bone marrow-derived endothelial pro­
genitor cell-derived vasculogenesis.38 Recent studies measured
increased levels of growth factors related to hypoxia-
induced angiogenesis (hypoxia-inducible factor-1 and vascu­
lar endothelial growth factor) 24–240 hours after grafting, a
process that may also contribute to host vessel ingrowth (see
Fig. 15.3).32
Maturation
Once the skin graft is completely integrated, the same graft
and surrounding tissues remodel and contract, similar to the
last phase of wound healing after re-epithelialization is com­
plete. Skin grafts take at least 1 year to complete maturation,
with the extension of this process continuing for several years
in burn victims and children. Scars from skin grafts can con­
tinue to improve for a number of years, often making pro­
longed conservative therapy worth considering.
Skin graft vascularization contributes to prevent underly­
ing tissue contraction. Fibroblasts from surrounding tissues
and from blood circulation become activated and repopulate
the wound at the interface between the graft and the recipient
site. As collagen is deposited, cross-linking allows the extra­
cellular matrix to resist mechanical insults. Fibroblasts develop
fibers called alpha-smooth-muscle actin (alpha-SMA) that
exert contractile forces on the extracellular matrix. The devel­
opment of alpha-SMA coincides with the differentiation
of fibroblasts into myofibroblasts and wound contraction.
During wound maturation, the epithelium from the edges of
the wound produces a basal lamina on the open surface while
sliding across and progressively covering the immature
granulation tissue.
During the remodeling phase, all immature blood vessels
necessary to support the initial phases regress and eventually
disappear. The remodeling phase of wound healing is the
longest, lasting from several months up to years.
Table 15.1  Definition of origin of the skin graft
Graft type
Graft origin: donor and recipient
Autograft
Same subject
Homograft
Same species
Different subject
  Isograft
Same genetic background
Allograft
Different subjects
Same species
Hetero- or xenograft
Different subjects
Different species
(Adapted from Andreassi A, Bilenchi B, Biagioli M, et al. Classification and
pathophysiology of skin grafts. Clin Dermatol. 2005;23.)
Fig. 15.4  Split-thickness donor sites. Split-thickness donor sites are commonly
chosen from the anterior thigh or abdomen. Color-matched and aesthetically less
evident areas can only be chosen if healthy skin is available. In burn patients with
only limited availability of nonaffected skin, skin will be taken from any part of the
body. Face and hands are preferentially spared from skin harvest. (Adapted from
Knipper P. Mission: plastic surgery under challenging conditions. Maîtrice
Orthopédique. 2002:118 and 2003:112.)

220
CHAPTER 15 • Skin graft
Table 15.2  Indications, advantages, and disadvantages of thin split-thickness skin graft (STSG), thick STSG, and full-thickness skin
graft (FTSG)
Indications
Advantages
Disadvantages
Thin STSG
Debrided burn wounds
Chronic wounds with less
vascularized wound beds
Exposed flap areas
Acute well-vascularized wounds
Fast donor site re-epithelialization
Multiple possibilities to reharvest the same
area
Good graft take
Contraction of the skin graft
Graft quality limited because of
minimal dermal thickness
Thick STSG
Same indications as thin STSG
Less secondary graft contraction compared
to thin STSG
Graft more stable because of thicker
dermal layer
Good graft take
Slower donor site
re-epithelialization
FTSG
Reconstruction of functional areas
such as in the face or hand
Noninfected, well-vascularized
wound beds
Minimal to no secondary graft contraction
Excellent skin quality, stability
Hair regrowth and skin appendage function
Limited availability
Nontake risk is higher in a less
vascularized wound bed
wounds this process leaves the body at risk of infection and
when it occurs around joints, this can lead to significant scar
contractures that affect functionality. For example, in anterior
neck wounds, the contractile processes can be so strong that,
over time, the chin can be fixed to the chest, often with a thick
scar. Also, wounds that are left open for months to years can
degenerate into skin cancer (Marjolin’s ulcer). For these
reasons, methods that rapidly facilitate wound coverage or
resurfacing are desired.
Skin grafting is still the gold standard to cover large areas
of skin loss. The concept is to take skin from an area where
the donor site will heal with minimal scarring and transplant
it to an area of need. As skin grafting always leaves some sort
of scar, donor site considerations are important when balanc­
ing the needs of the recipient site for a given skin graft.
Skin grafts can be of different origin (Table 15.1), from
different anatomical sites (Fig. 15.4), and can be harvested in
different thicknesses (Table 15.2). Depending on the histologi­
cal level of the graft the skin graft type is classified by thin
and thick STSGs, full-thickness skin grafts, and composite
grafts (see Fig. 15.2). Skin grafts are further classified accord­
ing to their thickness into thin (0.15–0.3 mm, Thiersch–Ollier),
intermediate (0.3–0.45 mm, Blair–Brown), and thick (0.45–
0.6 mm, Padgett). Skin grafts thicker than 0.6 mm usually
correspond to full-thickness skin grafts and are called Wolfe–
Krause grafts.42–44
Split-thickness skin graft
The thickness of the dermal layer classifies the STSG as either
thin or thick. An STSG consists of epidermis and a variable
amount of superficial to profound (papillary) dermis. As the
dermis is responsible for the viscoelastic property of the skin,
it is crucial for stability of the future skin. The amount of
dermis grafted is key to the outcome: body areas with high
mechanical friction are ideally grafted with thicker dermal
layers. If donor sites do not allow this, skin quality can be
improved with a combination of skin and dermal substitute
grafts.
Thin STSGs include the epidermis and a thin layer of the
dermis (see Fig. 15.2). STSGs are commonly taken from the
lateral thighs and trunk (see Fig. 15.4). They do not include
the full length of appendages and are therefore unlikely to
grow hair or to develop full sweat gland function. The main
advantage of thin STSGs is the reduced morbidity of the
donor site and the possibility of performing multiple harvests
from the same donor area about 2 weeks after the previous
harvest. Although thinner grafts allow for more frequent
reharvest, they result in additional wound contraction. The
clinician must weigh the advantages and disadvantages
of these conflicting goals when deciding the thickness of
the graft.
Fig. 15.5  Donor site preparation. Bleeding is one of the most important
complications of excision and grafting. To reduce the severity of bleeding during
excision, the fatty tissue under the graft can be infiltrated with a solution of
epinephrine diluted in saline (“tumescent technique”). (Modified from King M,
Bewes P. Skin grafts and flaps: the general method for split skin grafting. In: Primary
Surgery, Vol. 2. Trauma. Oxford: Oxford University Press; 2009. By permission of
Oxford University Press Inc.)
A
Wheals at the edge
of the graft area
B
Area of graft infiltrated
through wheals

221
Clinical application
placement of adhesive on the skin and an oscillatory move­
ment by the operator.
When possible, harvesting the skin graft first and covering
the donor site will avoid contamination from the wound.
When the excisional preparation of the recipient site needs to
be performed first, a separate instrument set-up for the donor
site can be considered. The size of the graft needed should be
accurately measured prior to harvest. The graft thickness can
be adjusted by a lever near the end of the dermatome between
0.1 and 1.0 mm. The surgeon presses the dermatome at 45° to
the skin surface on to the tissue and moves the device from
distal to proximal with uniform pressure and speed (see Fig.
15.7). A second assistant can pick up the skin graft with two
anatomical forceps during the harvest process to avoid
damage of the graft. If the desired length is taken, the derma­
tome will cut the edge when elevating it while running the
motor. Keeping the graft moist with saline-impregnated gauze
is of vital importance if not immediately grafted.
Larger skin grafts should be incised with an 11 knife mul­
tiple times to allow wound fluid drainage and prevent collec­
tions between the skin graft and the wound bed.
Thick STSGs include more dermis with a greater number
of full hair follicles and glandular structures (see Fig. 15.2).
These grafts will likely develop some hair growth and sweat
gland function about 2–3 months after grafting. Thick STSGs
are commonly selected to cover areas of high mechanical
friction, such as joints, plantar soles, and the palm. Since hair
regrowth is common in thick STSGs, the donor site should be
carefully chosen to avoid unpleasant hair growth. The sensi­
tivity and function of sweat glands are often better in thick
than in thin STSGs. Because of decreased nutrient diffusion,
thick grafts require a better recipient wound than thin grafts
during the revascularization process. Therefore, thick grafts
should be avoided in unhealthy wound beds such as in
chronic ulcers. The donor site usually heals with more obvious
scarring and discoloration but less graft contraction.
Technique
To reduce bleeding during skin harvest some surgeons prefer
to infiltrate the donor site area primarily with epinephrine
diluted in saline subcutaneously (tumescent technique: Fig.
15.5). If small to medium-sized areas of skin are needed and
a dermatome is not available, surgeons can skillfully take skin
grafts with a surgical knife or with the oscillating Goulian
knife (Fig. 15.6). The disadvantage of skin grafts taken manu­
ally is the difficulty of achieving uniform depth that can result
in aesthetically unpleasant donor and recipient site skin
pattern. To increase the uniformity and expedite the harvest
of skin grafts, a number of electrical or air-powered derma­
tomes have been designed to take uniform small to large skin
grafts. Powered dermatomes have adjustable guards to set the
graft thickness. There is a fair amount of variability in thick­
ness depending on how hard the operator pushes on the
dermatome. Drum dermatomes are precision instruments
that can take large graft areas reliably (Fig. 15.7). They require
Fig. 15.6  Split-thickness harvest with a manual knife. Alternatively, if no
electrically driven dermatome is available, skin grafts can be carefully harvested
with a manual knife. This procedure requires experience and harvest of even
thickness is difficult. (Adapted from Knipper P. Mission: plastic surgery under
challenging conditions. Maîtrise Orthopédique. 2002:118 and 2003:112.)
Fig. 15.7  Split-thickness harvest and grafting. (A) Split-thickness skin graft
(STSG) harvest with an electrically driven dermatome at the anterior thigh. (B) The
skin graft should be positioned flat on the mesh template: this can be perforated by
multiple slits to (C) expand the graft up to six times its original size. (D) Meshed
STSGs are ideal to cover large and uneven wounds. Stapler fixation is a time-saving
method to fix large grafts. (Adapted from Orgill DP. Excision and skin grafting of
thermal burns. N Engl J Med. 2009;360:893–901.)
A
B
C
D

222
CHAPTER 15 • Skin graft
(Fig. 15.9). This process takes longer with higher mesh
expansion ratios. Since grafted cells excrete growth factors,
underlying granulation tissue will be stimulated until full
re-epithelialization occurs. Aesthetically unpleasant hyper­
granulation in the open areas of the mesh are therefore more
often seen in large mesh ratios often leading to an uneven
cobblestone-like skin relief (Fig. 15.10). Meshed skin grafts
leave unsightly long-term results that need to be considered
when selecting this technique. Very thin meshed skin grafts
used in combination with dermal substitutes or keratin­
ocyte cultures are other strategies to mitigate the result (see
Fig. 15.8).
Full-thickness skin graft
Full-thickness skin and composite grafts are limited in avail­
ability but show excellent function and sensitivity after
engraftment. Full-thickness grafts should be considered in the
Meshed skin graft
STSGs can be enlarged up to six times their original size.
Enlargement of the graft can vary from just a few manually
applied perforations with an 11 blade to a systematic enlarge­
ment with a hand-powered meshing device (mesher) that
applies multiple slits at regular intervals (see Fig. 15.7).
Meshed grafts are often used following large burns when the
wound area exceeds available healthy donor sites. Meshed
skin grafts are also very helpful to cover irregular geometric
surfaces, such as around joints, as they minimize folds in the
graft. Development of contractures should be taken into
consideration in functional areas. If meshing is not necessary
or should be avoided in important aesthetic or functional
areas, such as face, neck and hands, the graft should be per­
forated multiple times to allow fluid removal under the graft
(pie-crusting) that can minimize the risk of hematoma, seroma,
or infection under the graft. Unmeshed STSG can achieve
excellent aesthetic and functional results (Fig. 15.8). Using
different mesh templates, from 1 : 1 to 1 : 9, can regulate the
extent of the enlargement of meshed grafts. The most com­
monly used mesh ratio is 1 : 1.5 in smaller wounds, while a
mesh ratio of 1 : 3 and 1 : 6 is often needed to cover large burns.
Meshing devices are manual and come with different
plastic templates where the skin graft is placed on upside
down. The graft should be taken with anatomical forceps
to avoid mechanical damage. The mesh gaps will be
subsequently filled by keratinocytes from the skin stripes
Fig. 15.8  Non-meshed split-thickness skin graft coverage 18 months after
debridement of 2nd deep burn injury of the hands. Note excellent aesthetic and
functional results.
A
Mesh graft
B
Direction of re-epithelialization
Fig. 15.9  Meshed split-thickness skin graft (STSG) and re-epithelialization. The
pattern of the meshed STSG is evident even after completely healed skin and is
more evident with the enlargement ratio used. Therefore, surgeons possibly prefer to
expand with 1 : 1.5–1 : 2 ratios as maximum. (A) The meshed skin graft can be fixed
with staples or sutures. (B) Open surfaces will be gradually re-epithelialized from
the skin stripes. In largely expanded grafts the stimulation of the wound bed from
the engrafting cells leads to hypergranulation, resulting in an unpleasant aesthetic
pattern. (Adapted from Orgill DP. Excision and skin grafting of thermal burns. N Engl
J Med. 2009;360:893–901.)

223
Clinical application
reconstruction if the patient is comfortable with an aesthetic-
like intervention.
In hand reconstruction, elbow crease and wrist fold grafts
have been described but should be avoided in cultures where
these donor site scars may result in stigmatization of the
patient as they can be associated with suicide. Hypothenar
skin is useful for glabrous reconstruction but can leave a
painful scar that can cause an unpleasant sensation if the hand
is positioned on a table in a relaxed position. Therefore, full-
thickness skin graft from the hypothenar area should be
harvested elliptical with the main axis and slightly more
dorsal in relation to the glabrous–skin border (see Fig. 15.11).
Full-thickness skin grafts are taken in an area where loose
surrounding skin is available to achieve primary closure. Skin
grafts can be designed elliptical and excised with a knife.
Harvesting should be carried out trying not to elevate the
underlying tissue. Most of the full-thickness grafts need defat­
ting and this can be easily performed by spreading the graft
over the index finger and trimming the fat tissue tangentially
to the skin. Defatting of the graft will encourage graft take
(Fig. 15.12).
Composite graft
Composite grafts include a layer of subcutaneous fat tissue
under the dermal and epidermal layer. The donor sites are
principally the same as the full-thickness donor sites. Since fat
tissue is less vascularized and more vulnerable to ischemia,
optimal revascularization is needed in order to achieve graft
survival. Composite grafts can be used in children as they
show a remarkable capacity to revascularize thicker grafts.
Some surgeons use composite grafts to reconstruct the nasal
tip, the alar, and the columella in cleft lip patients.45
Over time, the appearance of skin grafts tends to improve
in both color and texture. Nevertheless, skin grafts rarely have
the aesthetic appearance of normal skin and patients should
be advised about the likely final appearance of the graft.
Skin fixation and dressing
Once the autologous skin is grafted on to the wound site the
revascularization depends on multiple factors. One of the
most important factors to achieve stable taking is the immo­
bility of the graft during the revascularization process. An
open technique requires labor-intensive monitoring on the
graft and any fluid that is formed beneath the graft is rolled
out with a cotton-tipped applicator. More often, skin grafts
are fixed through a series of sutures and overlying compres­
sive dressing materials (bolster: Fig. 15.13). Scattered sutures
through the graft on to the wound bed can additionally
immobilize larger skin grafts. If large and multiple skin grafts
are placed, as frequently needed in burn victims, fixation can
be performed with staplers to shorten operation time. Staples
are painful when removed and may be overgrown by skin,
especially in large skin grafts. Vacuum-assisted pressure
devices can be used with a protective interface of petroleum
gauze or a silicone sheet to permit continuous compression
on to the graft and fluid removal. The suction dressing is
especially useful if fast mobilization is desired in patients with
wounds in joint regions or the lower extremities (see Fig.
15.13). Compression to stabilize the graft on to the wound bed
should be performed until 5–10 days after grafting, when the
graft is usually stable and wound areas are completely closed.
reconstruction of aesthetically dominant (face) or functionally
important (hand) areas. Full-thickness grafts from the retro­
auricular region and above the eyebrows are an excellent
choice to maintain tissue quality and color of the surrounding
skin in the face (Fig. 15.11). If needed, foreskin can also be
used and in adults retroauricular skin is helpful in face recon­
struction. Also, excess skin from the upper eyelid and sub­
mental area can be taken into consideration for full-thickness
Fig. 15.10  Uneven skin relief, “cobblestone” pattern in a left forearm 3 years after
deep burn injury, debridement and coverage by a 1 : 3 ratio meshed split-thickness
skin graft.
Fig. 15.11  Full-thickness donor sites. Full-thickness skin graft (FTSG) donor sites
are limited and require primary wound closure or split-thickness skin grafting after
harvest. FTSG are indicated in the reconstruction of smaller lesions in aesthetic
(face) or functional areas (hand). Larger FTSG can be taken from the buttock fold
and the infra-abdominal fold. Ideal for reconstruction of the hand is the hypothenar
area and the anterior wrist fold. The main axis of the elliptically shaped hypothenar
graft should be positioned slightly dorsal to the glabrous–skin border to avoid a
hypersensitive scar. For face reconstruction, FTSGs are taken from the retroauricular
or, often used in children, the superior eyebrow regions for optimal color match.
The inguinal fold is frequently used because of good aesthetic outcome at the
donor site. Other areas are the subclavicular, the infra-abdominal, and the elbow
fold as well as the inner upper arm. (Adapted from Knipper P. Mission: plastic
surgery under challenging conditions. Maîtrise Orthopédique. 2002:118 and
2003:112.)

224
CHAPTER 15 • Skin graft
Fig. 15.12  Full-thickness skin graft (FTSG) harvest and preparation. FTSGs should be designed elliptically to achieve primary wound closure without deforming
surrounding tissues. This fact is usually given if a length : width ratio of 1 : 3 is followed. (A) After sharp excision of the graft the surgeon should elevate the graft if possible
without fat tissue and protect the graft by handling it with a skin hook or anatomical forceps. (B) Defatting is an important process to avoid fat necrosis after grafting and to
facilitate direct revascularization of the wound bed. The graft can be easily defatted with scissors by stretching the graft upside down over the index finger. (C) To allow fluid
exit from the wound bed, FTSG should be incised with a sharp knife in multiple sites. (Adapted from Knipper P. Mission: plastic surgery under challenging conditions.
Maîtrise Orthopédique. 2002:118 and 2003:112.)
A
B
C
Fig. 15.13  Fixation of a skin graft. Skin grafts require precise contact with the wound surface, and fluid collections and micromovements are to be avoided. A bolster
dressing is an excellent method to press and stabilize smaller skin grafts on to the wound, particularly in the face or hand areas. (A) The graft is placed and sutured on to
the wound and sutures are left intentionally long. (B) A first layer of nonadhesive fat dressing is placed on the graft and covered with a bolster of cotton or gauze that is
sutured face to face over the second layer. (C) The second layer will exert mild pressure on to the graft that stabilizes the graft and allows fluid exit into the bolster dressing.
(D) The bolster dressing will precisely adapt the skin graft on to the wound bed to optimize the conditions for the revascularization process. (E) Vacuum-assisted closure
dressing to fix skin grafts: the fixation of the skin graft is an elegant method, especially if larger and uneven areas that cover joints are grafted. Continuous suction and
compression on to the wound bed ensure fluid removal and stabilization of the graft. The skin graft will be fixated as usual and the first dressing should be either a
nonadhesive perforated silicone dressing or a petroleum gauze to avoid maceration of the graft by the open polyurethane foam. Some surgeons use the moist white foam
without interface to fix the graft. (A, C Adapted from Knipper P. Mission: plastic surgery under challenging conditions. Maîtrise Orthopédique. 2002:118 and 2003:112. B,
Adapted from Chase RA. Atlas of Hand Surgery. Philadelphia: WB Saunders; 1974.)
A
B
C
D
E
To vacuum
Polyurethane foam
Adhesive cover
Porous intermediate layer