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free flaps. Plast Reconstr Surg. 2007;119(7):2092-2100.
Neligan PC. Role of thrombolysis in free-flap salvage. J Reconstr
Microsurg. 2003;19(8):523-530.
Vascular complications and microvascular free flap salvage: the
role of thrombolytic agents. Microsurgery. 2011;31(7):505-509.
surgically uncorrectable venous congestion after free flap breast
reconstruction. Microsurgery. 2014;34(7):522-526.
therapy for patients with surgically unsalvageable venous
obstruction after revascularized free tissue transfer. Arch
Otolaryngol Head Neck Surg. 2002;128(8):960-965.
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CHAPTER 6 Concepts of Skin Grafts
and Skin Substitutes
Nicholas Calotta and Michele A. Manahan
KEY POINTS
Skin grafts and skin substitutes convey immense
versatility in wound management. Wounds of large size in
any location with a variety of exposed anatomic
structures and contours may be successfully skin grafted
when vascularized tissue is present throughout the graft
recipient site.
Skin grafts heal by three historically denoted processes:
imbibition, inosculation, and revascularization. Modern
understanding emphasizes early fluid diffusion into the
skin graft followed by vascular ingrowth.
Choice and execution of surgical technique,
encompassing recipient site and patient preparation,
thickness of tissue harvest, meshing, and dressings, play
integral roles in ensuring successful outcomes.
Modifications to standard techniques can expand
indications, and special circumstances should always be
considered.
Split-thickness (partial dermal harvest) and full-thickness
(complete dermal harvest) skin grafts possess different
characteristics based on the dermal component. Splitthickness grafts demonstrate less intraoperative
shrinkage, decreased metabolic needs, and more longterm scar contraction, pigment changes, and
susceptibility to trauma.
Skin substitutes serve critical functions both as
temporizing measures and as essential elements in
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converting wounds to candidacy for skin grafting.
INTRODUCTION
Many plastic surgical endeavors rely upon delivery of materials to
areas of tissue deficiency. The “reconstructive ladder” implies that
reconstruction planning should begin with the most basic and
straightforward approaches, and then proceed in steplike fashion to
progressively higher levels of complexity.1 As such, skin grafts and
skin substitutes represent a low rung on the ladder, above healing by
secondary intention and primary closure, and they stand as a basic,
core principle of wound management. Over time, other concepts of
wound treatment planning have been proposed, including the
reconstructive triangle2 and elevator.3 In all of these, applications of
nonvascularized tissue or material to an area of deficiency are
acknowledged as important treatment modalities.
This chapter will present autologous skin grafts, allografts and
xenografts, autogenous skin substitutes, and skin substitutes of
other compositions. Indications for use and technical considerations
will be emphasized. The evolution of the field will also be discussed.
DEFINITIONS
Skin grafts are generally thought of as either “split thickness,”
including the epidermis and some portion of the dermis, or “full
thickness,” including the epidermis and the complete thickness of the
dermis (Figure 6.1).4 It is generally believed that increasing the
proportion of the dermis increases contraction of the graft as it is
being surgically manipulated, but decreases contraction of the graft
as it heals, leading to improved scar, mobility, and elasticity.
5,6
Fullthickness grafts may also provide better color match with less
hyperpigmentation in the long-term than split-thickness grafts.
Therefore, full-thickness grafts are more commonly used in the hand
and face where surface areas of wounds are small and functional
and esthetic considerations are large.
5,6
Full-thickness grafts do,
however, require consideration of donor skin “match” to the recipient
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area regarding factors like sun exposure and native skin thickness
and quality. Full-thickness grafts are more limited regarding size,
given the need to close the donor wound.
6
FIGURE 6.1 Cross section of human skin demonstrating
differences between full-thickness and split-thickness skin
graft.
HISTORICAL PERSPECTIVES
Reports of skin grafts exist from the Egyptian Empire’s Ebert
Papyrus (circa 1500 bc). The often-referenced Sushruta Samhita,
famed for descriptions of many plastic surgical concepts, describes
skin graft use 3000 years ago. By the second century ad, Celsus and
Galen, Greek physicians, had both used skin grafts for patients’
facial wounds, and Celsus used skin graft techniques for foreskin
reconstruction. Skin grafting was rediscovered in the early 1800s.
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Early reported cases involved nasal wounds and burns. A Swiss
surgeon, Reverdin, is credited with developing the “pinch graft”
technique in the mid-1800s, whereas the split-thickness skin graft is
attributed to Ollier of France and similarly to Thiersch of Germany,
leading to the term “Ollier-Thiersch graft,” with minimal dermal
inclusion. In the 1870s, several German surgeons, including Wolfe,
Lawson, and Krause, described and popularized the use of fullthickness skin grafts, particularly for eyelid repair and other
circumstances where split grafts were failing to meet goals. Evolution
of split-thickness skin graft techniques continued into the early 1900s
with Blair and Brown presenting a technique including more
intermediate thicknesses of dermis.
6
In the early to mid-1900s, skin graft expansion was developed.
6
Meeks, practicing in South Carolina, developed a micrograft
technique to expand surface area treatable by a particular donor site
size in the 1950s.6 This was quickly overshadowed by an Atlantabased physician publishing “The Mesh Skin Graft” in Plastic and
Reconstructive Surgery in 1964, documenting his use of a meshing
machine.7 American surgeon Earl Padgett first described the use of
a manual dermatome for skin graft harvest in 1941. Just a few years
later, another American surgeon Harry Brown invented the first
powered dermatome, the modern Zimmer dermatome forerunner,
while a prisoner of World War II.
8
When autologous skin is unavailable or wounds are inhospitable,
skin substitutes may be considered. Historical attempts at use of
allografts (from other humans) or xenografts (from other species)
failed until the mid-1900s. Shortly thereafter in the 1960s, use of
porcine xenografts become popular for temporary wound
management.6 True skin substitutes likewise have a relatively short
history. Cell culture to create tissue mimicking epidermis was first
accomplished in 1975, and human cultured epidermal autografts
(CEAs) were first used in the 1980s. CEA remains an extant option;
however, time has not solved the problems of extended chronology
for culture, operative difficulties with material handling, and long-term
clinical fragility, blistering, and regrafting incidence.
6,9
Also in the
1980s, uncultured keratinocytes were first suspended in a fibrin
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matrix and used to treat chronic wounds.6 The first dermal analog,
Integra (Integra LifeSciences, Princeton, NJ), was also developed in
the 1980s.
6
FUNDAMENTALS OF SKIN GRAFT BIOLOGY
Skin grafts require early nutrition and eventual revascularization from
the wound bed into which they are placed to achieve graft survival,
or “take.” This occurs in classic steps supported by historical
literature. These are plasmatic or serum imbibition, inosculation, and
revascularization.
4
Imbibition was first described in the 1800s, based on the concept
of nutrient diffusion to skin graft cells from the fluid of the underlying
wound bed.4 An alternate view holds that the serum simply
preserves moisture and vessel patency for subsequent stages.4 In
either case, the conversion of plasma fibrinogen to fibrin assists in
graft adherence.4 In the earliest phase, grafts become edematous
and metabolism becomes anaerobic.
4,10
While generally lasting 24 to
48 hours, it can last for several days in poor wound healing
environments.
4
Inosculation, described as development of connections between
existing donor and recipient blood vessels, has been revised to more
accurately reflect microvascular capillary angiogenesis at the fibrin
interface of the wound, occurring after 48 to 72 hours.
4,11
This
process accelerates between days 3 and 7 and decelerates between
days 7 and 10.
4,11
Revascularization has been proposed to occur via
several mechanisms, including anastomoses between existing donor
and recipient vessels, wound vessel ingrowth and new
vasculogenesis with native graft vessel degeneration, and wound
vessel ingrowth with endothelial cell migration leading to
replacement of the graft endothelium.4 Current thinking emphasizes
angiogenesis through the fibrin interface beginning about 1 day post
graft, with reperfusion of the native circulation beginning within 2 to
3 days until roughly day 10.
4,12
As skin grafts heal, the epidermis initially increases in thickness,
because of cell swelling, cell migration, and accelerated mitosis. By
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day 4 through week 4, increased epidermal cell turnover leads to
proliferation and desquamation. Likewise, dermal structures
demonstrate increased turnover. Fibroblasts populate the dermis
from the wound. Dermal collagen demonstrates increased turnover.
Elastin degenerates within a few days and begins to regenerate at 4
to 6 weeks.
4
INDICATIONS
As discussed, skin grafting is one of the oldest and most widely
practiced methods of achieving cutaneous reconstruction for wounds
of many different etiologies across disparate anatomies. Skin grafts,
by definition, transfer to a recipient site without independent blood
supply. They are, therefore, fully dependent on the quality of the
local wound environment for survival and successful reconstruction.
Generally, skin grafts are indicated when two conditions are
present: (1) the only missing tissue component, or the most critical
missing component, is skin; and (2) the wound can produce
granulation tissue independent of surgical intervention. Wounds
missing a substantial volume of subcutaneous tissue or muscle,
especially functional muscle, are not ideal esthetic candidates for
skin grafting alone, as a skin graft is a two-dimensional
reconstruction and wounds of this nature benefit from a threedimensional solution. Similarly, wound beds that have shown poor
capacity for capillary rich granulation tissue formation are not primed
for reliably satisfactory outcomes from skin grafting alone.
12
Caveats to these general principles must be considered. While
skin grafts used in thicker wounds do not carry esthetic benefits, they
serve vital functions in patients in whom alternate methods of more
composite tissue transfers are not available. In these circumstances,
patients should be counseled regarding limitations to appearance
conveyed by a “thin” reconstruction in a “thick” wound. Additionally,
wounds that are healthy enough to support skin grafts and skin
substitutes may heal on their own, emphasizing the need to consider
donor site morbidity during surgical planning.
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The immense versatility of skin graft techniques is not to be
overlooked. Donor sites can be considered from essentially any part
of the body, including scalp and scrotum. As will be further
discussed, skin grafts can treat wounds of large surface areas and
overlying a host of structures, from vascularized bone and tendon to
muscle, fascia, and even adipose. Irregularly contoured and shaped
recipient deficits are easily covered with skin grafts and skin
substitutes.
The Wound Bed
The initial consideration when indicating a patient for skin graft
reconstruction is the quality of the underlying wound bed. Because a
free skin graft lacks any intrinsic source of nourishing blood, the
underlying wound bed will provide sole sustenance for the
transferred tissue. Granulation tissue is the clinical manifestation of a
wound bed environment suitable for take. This nascent healing
tissue can supply copious fibrin that will mature into the connective
tissue that anchors the graft in the long term; inadequate
endogenous fibrin will put the graft at loss for excessive shearing
forces. Granulation tissue is also densely populated with
regenerating capillaries, supporting the processes of imbibition and
inosculation that predominate prior to true neoangiogenesis.13 Not
infrequently, the wound to be grafted is acute and there is no
opportunity to assess for the quantity or quality of granulation tissue.
When this situation arises, knowledge of the intrinsic regenerative
capacity of human tissues is essential for obtaining reliably excellent
outcomes.
The ideal tissues for receiving skin grafts are muscle and fascia.
14
These planar, richly vascularized tissues consistently accept skin
graft and provide high probability of uneventful take. Axial blood
vessels are also excellent recipient sites for skin grafts from a
biologic perspective because of vascularized adventitia, though the
decision to cover such critical structures with skin only is a more
nuanced decision that must be handled on a case-by-case basis.
Wounds in which the deepest exposed layer is adipose tissue
represent a spectrum in terms of propensity for skin graft take. The
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subcutaneous fat of the thorax, abdomen, and extremities is
inconsistently vascularized.15 As such, skin graft take is highly
dependent on other local factors such as host medical morbidities,
underlying wound characteristics (eg, prior radiation, infection, shear
forces), and type of graft used. Fat tissue in the face, and to some
extent the neck, is richly vascularized and will often accept skin
grafts as readily as muscle or fascia.
15
Challenging wound bed tissue types to prognosticate for graft take
are bone, cartilage, and tendon. These exposed structures are most
common in the limbs but can of course be found throughout the
body, especially in cases of trauma or neoplastic diseases. The most
important consideration when evaluating for the candidacy for skin
grafting is the presence of vascularized periosteum, perichondrium,
and paratenon (visceral or parietal). These investing layers provide
nourishing blood for the underlying tissue; their absence indicates
deranged metabolism for the tissue, whereas their presence points
to a wound bed with satisfactory intrinsic regenerative capacity.
16
There are a few notable exceptions to this, however. The bone of the
hard palate and the orbit can be readily skin grafted even in the
absence of these nourishing soft-tissue layers.17 Similarly, exposed
medullary bone can be carefully grafted, a fact which is most often
leveraged in skull reconstruction when the diploë is intentionally
exposed and covered with skin graft.
18
Beyond the nature of the tissues that require cutaneous coverage,
several characteristics of the wound itself are important to consider
prior to performing skin graft–based reconstruction. Devascularized
tissue must be debrided as a matter of providing perfused tissue for
revascularization and reducing the probability of infection. Infection
must be overcome by medical and/or surgical means. The
development of bacterial infection and the associated tissue-toxic
bacterial virulence factors combined with the host inflammatory
response to infection combine to create a particularly hostile
environment for orderly graft take. Historical teaching recommending
quantitative cultures with less than 1 × 105 organisms to demonstrate
absence of infection prior to wound closure has become more
debatable over time but is still valued by many practitioners.
19
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Finally, radiation injury must be considered. The pathologic
response to external radiation cannot be overstated. Careful
observation for sequelae of radiation injury in the tissue surrounding
the wound provides invaluable information about the potential for
granulation, and thus graft take, in the wound. Whereas plastic
surgery dogma precludes skin grafting in irradiated wounds because
of a perceived vascular compromise of these wounds, there have
been at least two large series published from high-volume centers
demonstrating adequate skin graft take in more than 85% of
patients, eliminating the need for further operations.
20,21
This is in
comparison to older literature that details a skin graft failure rate as
high as 100%, with approximately 80% of patients requiring further
operative treatment for wound coverage.
22,23
These advances impact
oncologic patients commonly receiving radiotherapy as an adjunct to
surgery, like extremity sarcoma extirpation and head and neck
cancer treatment. Much of this paradigm reversal is attributed to the
widespread utilization of negative-pressure therapy as a bolster
technique with all the associated enhancements in wound
physiology.21 Another contributing factor is the evolution of
radiotherapy to smaller overall doses, fractionation,
hyperfractionation, and the refinement of indications for
brachytherapy.
24
The Skin Graft
Full-thickness grafts are well suited for restoration of the entire
dermal-epidermal unit at the recipient site. Most commonly, grafts of
this design are used in head and neck reconstruction or flexural
resurfacing (eg, web space contractures), where thickness and
texture as well as relative resistance to secondary contracture are of
greatest importance. Limited amounts of full-thickness dermis can be
harvested and closed primarily without necessitating a split-thickness
graft to cover the donor site. Common harvest sites include
postauricular, upper eyelid, supraclavicular, inguinal, and medial
antebrachial skin. The additional thickness of the dermis increases
metabolic activity of the graft compared to thinner split-thickness
grafts, potentially increasing healing challenges. Moreover, the
deeper elements of the dermis are less densely vascularized. Taken
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