Skin Replacement
Skin Functions
1) Protective Barrier – trauma, radiation, evaporation, microbiological
2) Immunological surveillance
3) Thermoregulatory
4) Metabolic – vit D
Classification
1) Permanent
a. Autografts
i. FTSG – ideal but limited donor sites
ii. SSG – coverage increased by
1. Meshing
2. Meek micro graft technique (sandwich technique)
a. use of a special dermatome and prefolded
gauzes to obtain a regular expansion of autograft
squares from small pieces of split skin grafts –
1:9 expansion
iii. Cultured epidermal autograft
b. Flaps
c. Biosynthetic
i. Epidermal
ii. Dermal
iii. Composite
2) Temporary
a. Allograft
b. Xenograft
c. Biosynthetic
Well recognized that any successful artificial skin or skinlike material must replace all
of the functions of skin and, therefore, consist of a dermal portion and an epidermal
portion.
The epidermis is required to sustain life but the dermis provides quality of life.
AUTOGRAFT
Cultured epidermal autograft
Major limitations, as follows:
(1) at least 3 weeks is needed for growth of cultured epidermal sheets in the
laboratory, thus delaying the coverage of wounds;
(2) epidermal sheets need to be grafted on a clean wound bed because they are highly
sensible to bacterial infection and toxicity of residual antiseptics;
(3) the success of the treatment strongly depends on the dexterity of the laboratory
and surgical teams, from the production of the sheets to their graft and care after
grafting because this material is very fragile;
(4) the regeneration of the dermal compartment underneath the epidermis is a lengthy
process, and skin remains fragile for at least 3 years and usually blisters;
(5) the aesthetic aspect of the healed skin is less acceptable than the one obtained with
a split-thickness graft.
Best used in conjuction with a dermal substitute – either deepithelialised cadaveric
skin or Integra.
ALLOGRAFT
Cadaveric Skin
 Structurally and functionally, the best temporary skin replacement is fresh human
cadaver allograft skin.
 However, availability is limited due to the risk for transmission of disease and
difficulties associated with handling and transporting the material.
 For this reason, frozen human allograft skin is more commonly used.
 Skin is usually harvested within 24 hours of death at a thickness of 0.015 inches.
 The harvested skin is frozen in a cryopreserved fluid containing 10% glycerol and
is stored in liquid nitrogen vapor.
 Once thawed and placed on the excised wound bed, cadaver skin effectively
closes the wound and begins to prepare the area for definitive grafting with the
patient's skin. After allograft skin has adhered to the wound bed, it is removed and
usually will leave a vascularized wound base to accept an autograft, increasing the
chance that the autograft will be successful.
 The immunosuppression that occurs in large bums allows the allograft to remain
in place for several weeks without rejection.
 An excision of allogeneic epidermis can be performed with a dermatome to only
maintain the allogeneic dermis on the wound. Because nonliving dermis alone
may not be rejected, autologous cultured epidermal sheets can be grafted onto it,
thus greatly enhancing healing.
 Cultured epidermal sheets grafted onto homograft dermis display early rete ridge
development and anchoring fibril regeneration, in addition to a graft take of 95%.
 Disadvantages
(1) Limited supply
(2) Quality of the allograft may vary, depending on the age of the donor and the
body location of the harvested skin. Prolonged storage in ultralow temperature
freezers may diminish allograft viability.
(3) Epidermal slough has been observed with frozen allografts. Rarely associated
with the use of fresh allograft.
(4) Potential for disease transmission. Disease transmission had been reported in
association with donor allografts.
Allogenic Cultured Epithelial Autograft
 allogeneic cultured epithelial sheet grafts do not survive.
 Even when the allograft was depleted of Langerhans cell, the rejection
occurred in mice after 14-16 days.
 Readily available cultured allografts transplanted on deep partial-thickness
skin burns induce faster healing of the wound promoted by the residual
resident keratinocytes.
 Thus, the allograft may favor the proliferation and the differentiation of
spontaneously regenerating epithelium. Allogenic cultured epithelial sheets
can also be frozen for storage and easier transportation without impairing their
graft efficiency.
Amniotic membrane
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Human amniotic membranes obtained from the placenta after delivery have been
used for decades to cover burn wounds.
Readily available in large supply in major hospitals
Can be prepared relatively inexpensively.
They possess most of the characteristics of an ideal skin substitute: excellent
adherence to the wound, very low immunogenicity, decrease of pain, bacterial
control, and stimulation of healing.
A great advantage of the amniotic membrane is its translucency, allowing
inspection of the wound.
Can be applied on superficial second-degree burns, donor sites, and deep seconddegree burns after early debridement.
Useful to cover 1:3 meshed autografts, and they have been reported to be
extremely effective in sterilizing contaminated wounds and cleaning burns of
bacteria within 3-5 days.
Have to be changed daily and need to be covered with gauze to prevent
desiccation because they display less efficacy in preventing water loss compared
with homograft or xenograft.
They do not allow long-term coverage and could be dissolved early by the wound.
Amniotic membranes can be kept refrigerated for 6 weeks, or they can be frozen
for longer storage and banking purposes.
Acellular human dermis
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Healthy human dermis with all the cellular material removed.(Alloderm)
Prepared from cadaver skin by extensive washing and purification followed by
high-dose x-ray radiation and either deep freezing or glycerol preservation.
Better take with thinner overlying skin grafts
Very expensive.
XENOGRAFTS
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Tissues of animal origin have been used for thousands of years to cover extensive
wounds.
Xenografts achieves only temporary wound coverage but its unlimited availability
makes it a favorable wound covering.
Porcine skin is the most common source of xenograft because of its high
similarity to human skin.
Sterility is an essential concern with xenogeneic tissues transplanted on wounds.
Ionizing radiation +/- freeze-drying helps sterility, decrease the antigenic
properties of the pigskin graft and to increase its potential to inhibit bacterial
growth.
Pigskin usually promotes scar-free healing, with an average healing period of
about 10 days. In addition, pigskin provides a suitable overlay to cover widely
meshed (1:8 to 1:12) autografts.
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Ideal properties:
1) Be hemostatic and possess good adherence to any wound bed (including
cartilage and bone surfaces); fully cover the wound surface without any dead
spaces
2) Adhere immediately to the wound borders
3) Cover the whole wound area and protect it against infectious agents and the
loss of water and tissue fluids
4) Cover the wound area, reducing or eliminating pain
5) Lack any specific inflammation-stimulatory agents and not produce any
foreign body reaction, granuloma formation, or acute or chronic immunologic
rejection
6) Serve as a natural matrix for host granulation tissue formation and coordinate
fibroblast proliferation and angiogenesis with early tubular formation and
capillary development
7) Serve as a natural surface, promoting host epithelial cell proliferation,
reepithelization, and basal membrane structure development, and create a
stable connection between the new, developed connective tissue and the new,
proliferated epidermis
8) Promote a normal epidermal differentiation and enhance the maturation of
epidermis, which covers the healing wound (natural collagen matrix)
9) Because of 1-7, protect against both the contracture of wound borders and
typical scar formation
10) Be fully transparent and allow excellent clinical observation of the wound area
and the healing process
SEMI-SYNTHETIC DRESSINGS
Acellular matrices
Integra
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a bilayer membrane composed of a dermal portion that consists of a porous lattice
of fibers of a cross-linked bovine collagen and glycosaminoglycan (GAG)
composite and an epidermal layer of synthetic polysiloxane polymer (silicone).
The GAG that is used is chondroitin-6-sulfate; the degradation rate of the
collagen-GAG sponge is controlled by glutaraldehyde-induced cross-links.
The collagen-GAG dermal layer functions as a biodegradable template that
induces organized regeneration of dermal tissue (neodermis) by the body and the
infiltration of fibroblasts, macrophages, lymphocytes, and endothelial cells that
form a neovascular network.
As healing progresses, native collagen is deposited by the fibroblasts, and the
collagen portion of artificial skin is biodegraded over approximately 30 days.
The silicone layer must eventually be removed by the surgeon and is usually
replaced by thin epidermal autografts during the 2-step transplantation.
At present, the Integra Dermal Regeneration Template is approved in the United
States only for the postexcisional treatment of life-threatening, full-thickness or
deep partial-thickness thermal injury where sufficient autograft is not available at
the time of excision or not desirable because of the physiological condition of the
patient.
Biobrane
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A biosynthetic wound dressing constructed of a silicon film with a nylon fabric
partially imbedded into the film.
The fabric presents to the wound bed a complex 3-D structure of trifilament thread
to which collagen has been chemically bound and cross-linked.
Blood/sera clot in the nylon matrix, thereby firmly adhering the dressing to the
wound until epithelialization occurs.
Advantages include adherence, safety, control of evaporative water loss,
flexibility, durability, bacterial barrier, ease of application and removal,
availability, hemostatic properties, and cost-effectiveness.
In comparison with pigskin and skin allografts, Biobrane showed superior wound
adherence.
The product has been found to significantly reduce local wound pain, to speed up
the healing process, and to significantly prevent bacterial colonization of the
wound surface.
TransCyte
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indicated for use as a temporary wound covering for surgically excised fullthickness and deep partial-thickness thermal burn wounds in patients who require
such a covering prior to autograft placement
consists of a polymer membrane and newborn human fibroblast cells cultured
under aseptic conditions in vitro on a nylon mesh.
Prior to cell growth, this nylon mesh is coated with porcine dermal collagen and
bonded to a polymer membrane (silicone). This membrane provides a transparent
synthetic epidermis when the product is applied to the burn.
As fibroblasts proliferate within the nylon mesh during the manufacturing process,
they secrete human dermal collagen, matrix proteins and growth factors.
Following freezing, no cellular metabolic activity remains; however, the tissue
matrix and bound growth factors are left intact.
The human fibroblast-derived temporary skin substitute provides a temporary
protective barrier. TransCyte is transparent and allows direct visual monitoring of
the wound bed.
Contains essential human structural and provisional matrix proteins,
glycosaminoglycans, and growth factors known to facilitate wound healing.
The Outer layer: synthetic epidermal layer is biocompatible and protects the
wound surface from environmental insults. It is semi-permeable to allow fluid
and gas exchange.
The Inner layer: bio-engineered human dermal matrix adheres quickly to the
wound surface. It contains essential structural proteins (type I, III, and V
collagen), provisional matrix proteins (fibronectin, tenascin, SPARC,),
glycosaminoglycans (versican, decorin), and growth factors (TGF-B1, KGF,
VEGF, IGF-1).
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In partial thickness wounds, the patient's epithelial cells can proliferate and
migrate across the wound, resulting in rapid wound healing
Allergic reactions to the polymer membrane and nylon mesh coated with porcine
collagen.
With repeated use, possibility of develoiping HLA associated rejection
Promogran
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a novel collagen spongy matrix containing oxidized regenerated cellulose (ORC).
Promogran has been designed to treat exuding wounds, including diabetic, venous
and pressure ulcers.
The matrix is composed of 45% ORC and 55% collagen.
Forms a conformable gel on contact with exudates.
The ORC/collagen matrix binds to metalloproteases in chronic wound exudate
without altering the activity of essential tissue growth factors, and it creates a
milieu for moist wound healing.
Because metalloprotease levels may be elevated in chronic wounds and contribute
to degradation of important extracellular matrix proteins and inactivate growth
factors, their binding into the ORC/collagen matrix may have a positive effect on
the physiological wound healing process.
Promogran has been found to significantly increase the healing ratio of diabetic
foot ulcers compared with a traditional moistened gauze procedure, especially in
ulcers of less than 6 months' duration.
It is a single layer construct and may require additional moisture control barrier to
complete the dressing.
Cellular Constructs
Orcel
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A bilayered cellular matrix in which human allogeneic epidermal keratinocytes
and dermal fibroblasts have been cultured in 2 separate layers into a type I bovine
collagen sponge.
Donor dermal fibroblasts are cultured on and within the porous sponge side of the
collagen matrix, while keratinocytes, from the same donor, are cultured on the
coated, nonporous side of the collagen matrix.
OrCel serves as an absorbable biocompatible matrix that provides a favorable
environment for host cell migration and has been shown to contain the following
cell-expressed cytokines and growth factors: FGF-1 (bFGF), nerve growth factor
(NGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin
1 (IL-1), interleukin 1 (IL-1), IL-6, human growth factor (HGF), KGF-1
(FGF-7), macrophage colony-stimulating factor (M-CSF), platelet-derived growth
factor alpha/beta (PDGF-AB), transforming growth factor  (TGF-), TGF-,
transforming growth factor 2, (TGF-2), and VEGF.
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OrCel is not intended to be a human skin replacement, and it does not contain
Langerhans cells, melanocytes, macrophages, lymphocytes, blood vessels, or hair
follicles.
DNA analysis performed on 2 OrCel-treated donor site patient tissue samples
showed no trace of allogeneic cell DNA after 2-3 weeks.
Apligraf
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Cells derived from human neonatal male foreskin tissue
bi-layered construct
The lower dermal layer combines bovine type 1 collagen and human
fibroblasts (dermal cells), which produce additional matrix proteins.
The upper epidermal layer is formed by promoting human keratinocytes
(epidermal cells) first to multiply and then to differentiate to replicate the
architecture of the human epidermis.
Unlike human skin, Apligraf does not contain melanocytes, Langerhans' cells,
macrophages, and lymphocytes, or other structures such as blood vessels, hair
follicles or sweat glands.
10 day shelf life
Dermagraft
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cryopreserved human fibroblast-derived dermal substitute composed of
fibroblasts, extracellular matrix, and a bioabsorbable scaffold.