WOUND COVERAGE WITH ALLOGENIC SKIN

One of the main differences between the cultured epidermal sheet and a split-
thickness autograft is the lack of the dermal structure from the cultured
autograftable sheets. The absence of dermis is perceived as the major cause for a
lower percentage of graft takes and higher fragility and blistering after epidermal sheet
transplantation compared to split-thickness autograft. A dermal component
protects the basal layer of the epidermis and has a significant impact on the
postgrafting biologic responses of the epithelial cells to the differentiation and wound-
healing processes.
After early debridement /of deep and extensive burns, temporary closure of the
wound is usually achieved with cadaver allograft before autografting with cultured
epidermal sheets. Instead of completely removing cadaver skin before sheet
transplantation, 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. Indeed, cultured epidermal
sheets grafted onto homograft dermis display early rete ridge development and anchoring
fibril regeneration, in addition to a graft take of 95%.

Knowing that devitalization of allograft reduces their antigenicity, the use of allogeneic
cadaver skin as a biologic dressing is now widely accepted and is usually preferred to synthetic
dressings. The preservation of allograft can be performed by different techniques, such as
freeze-drying, glutaraldehyde fixation, or glycerolization.
Cryopreservation of homografts with glycerol is the most popular method of cadaver
skin processing because freeze-drying is too expensive and glutaraldehyde fixation
has proven less efficient. Moreover, skin preservation can reduce the risk of virus
transmission from skin grafting, providing time to rid the donor skin of pathogens.
Indeed, incubation of cadaver skin for several hours at 37°C in glycerol displays a
significant virucidal and bactericidal effect. To provide sufficient cadaver skin instantly
accessible for the patient with a burn, skin banks, such as the Euro Skin Bank in
Beverwijk, The Netherlands, have been well developed through the years. However,
allogenic skin banking has a significantly higher cost compared with xenogeneic skin
banking and biologic dressings.
DRESSING CATEGORIES CURRENTLY MARKETED
IN THE UNITED STATES
Wound Dressings (Material Categories) No. 1
Products
I Gauzes (woven and nonwoven) 33
Gauzes l(impregnated) 25
Gauzes (nonadherent) 13
Gauzes (packing/debriding) 17
jCompression jbandages and system 24
Specialty absorptive 17
Composites 20
Wound fillers 10
Wound cleansers 28
Synthetic foams 26
Contact layers 7
Hydrocolloids 41
Hydrogels (amorphous) 30

Hydrogels (wafers) | 19
Hydrogels I (impregnated gauze) 14

Alginates 26
Collagen 9
 SYNTHETIC OR SEMISYNTHETIC DRESSING

SILICONES
Silicone dressings consist of chemically and biologically inert, usually transparent,
silicon sheets or gels. Some of the silicone membranes are porous to allow gas and
moisture exchange between the wound surface and the environment. Other silicone
membranes are nonpermeable to ensure a fully occlusive wound environment.
Silicone dressings not only work as antiadhesives but also may reduce
hypertrophic and keloid scarring. Silicone has been found to be useful in flattening of
scarring tissue; increasing elasticity; and reducing discoloration, making the scars more
cosmetically acceptable. Additionally, silicone or siliconized membranes have been found
useful in covering split-skin donor sites or fresh meshgrafts.

Earner films

Moreover, silicone membranes work as an epidermislike portion in combination

engineered skin substitutes (as previously mentioned)
Barrier films are protective polymers dissolved in a fast-drying carrier solvent,which,
ideally, should be noncytotoxic, be pain reducing on application to broken skin,
protect skin from loosing moisture or from exogenic fluids, protect from skin
stripping, and be compatible with clothing. Such dressings may be applied as fluids, which
quickly polymerize on the wound surface or as industrially prepared membranes made
mostly from polyurethane or polylactate.

Foams
Foams mostly consist of polyurethane porous sponges or polyurethane foam films with
or without adhesive borders. Most of them are suitable for use on light-to-medium exuding
wounds. Many types of foams may be left on the wound surface for up to 7 days,
depending on exudate volume. Foams are not recommended for any kind of dry
wounds. Besides the usual range of sizes, anatomically shaped dressings are
available for specific wound locations (eg, sacral region, heel).
Tissue adhesives
Tissue adhesives have been developed to exchange suturing in some, mostly small and not-too-
deep wounds that can heal by primary intention. Moreover, such products may be used in the
form of surface covering liquid bandages. Currently used tissue adhesives contain cyanoacrylate
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components, including bucrylate, enbucrilate, and mecrylate, which polymerize in an
exothermic reaction on contact with either a fluid or a basic substance. Such a process leads to
the forming of a strong, flexible, waterproof band.
Tissue adhesives are used for simple lacerations, which otherwise might require the
use of fine sutures, staples, or skin strips, producing cosmetic results similar or better
than traditional suturing. This is a needless and mostly painless method of wound repair
that does not require follow-up visits for suture removal.
Tissue adhesives provide the strength of healed tissue seen at 7 days. Special attention is
necessary to ensure that wound edges are appropriately adapted and that no adhesive passes
between wound borders.
Hyaluronic acid
Vapor-permeable films (also known as semipermeable films), made of materials
that can be found in some tissues, are now becoming popular wound dressings. Most of
them are made of industrially manufactured and purified hyaluronic acid. Hyalogratt 3D
and Laserskin (HYAFF-11) are indicated for use on diabetic foot ulcers and venous leg
ulcers. Entirely composed of a benzyl ester derivative of hyaluronic acid, they may be
used as membranes for direct wound dressing or as scaffolds for the cultivation of
fibroblasts and keratinocytes for further transplantation.

Hydrogels
Hydrogel dressings contain a large portion of water, often more than 70- 90%. They
have some important characteristics of an ideal dressing. Hydrogels can cool the surface of
the wound, resulting in marked pain reduction. Moreover, hydrogels maintain the moist
wound environment and are mostly suitable for use on dry or necrotic wounds or on lightly
exuding wounds. They are suitable for use at all stages of wound healing except for
infected or heavily exuding wounds. Hydrogels are a good alternative for classic wet
dressings. In some cases, however, hydrogels may macerate the healthy skin (mostly
wound border areas), decreasing the keratinocyte reepithelialization ratio or leading to
overwetting of split-skin donor sites. Hydrogels are available as sheet dressings or gels.
Hydrocolloids
Hydrocolloid dressings are much more complicated than hydrogels because they
contain a variety of constituents, such as methylcellulose, pectin, gelatin, and
polyisobutylene. Some of them also contain alginate. After contact with the wound
surface, hydrocolloids slowly absorb fluids, leading to a change in the physical state of the
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dressing and to the formation of gel covering the wound. Thus, they are called interactive
dressings.
Hydrocolloids ensure the moist wound environment, promote the formation of granulation
tissue, and provide pain relief by covering nerve endings with both gel and exudate. These
dressings are marketed with or without adhesive borders. Depending on the choice of
product, hydrocolloids are suitable for the dressing of both acute wounds and chronic wounds,
for desloughing, and for different stages of light-to-heavily exuding wounds.
Initially, hydrocolloid wound dressings need to be changed daily (depending of the exudate
level), but, once the exudate has diminished, dressings may be left on the wound surface for
up to 7 days. With a few exceptions, hydrocolloids require a secondary dressing to be
fixed in place. Hydrocolloids should not be used on infected wounds.
Calcium alginates
Alginates are highly absorbable biodegradable dressings derived from seaweed (eg,
Kaltostat, Tegagen, SorbSan, SeaSorb, Algisite M, Algosteril). They contain the building
blocks of mannuronic acid (M) and guluronic acid (G). The high M alginates are soft and gel-
like, whereas the high G alginates are more stable and ribbon- or rope- like. Large
quantities of alginates are used each year to treat exudating wounds, such as leg
ulcers, pressure sores, and infected surgical wounds. In addition P to controlling exudate by ion
exchange, alginates are believed to exert a bioactive effect by activating macrophages within
the chronic wound bed to generate proinflammatory signals (eg, tumor necrosis factor D
[TNF-D], interleukin 1, interleukin 6 [IL-6], interleukin 12).
This may then initiate a resolving inflammatory response characteristic of healing
wounds. Chronic wounds are now well known to be characterized by macrophage-rich
inflammation, and any putative macrophage defects probably relate to the functional
status of the macrophages present at the wound site.
In vitro studies have demonstrated that some dressings containing alginates can activate
macrophages, as evidenced by their increased production of TNF-D. Research is
currently underway to modulate alginate dressings to enhance these effects and to
incorporate antimicrobial silver into alginate preparations (eg, Acticoat
Absorbent). In addition, new preparations (eg, AGA-100) that have a reduced
cytotoxicity to cells, such as fibroblasts, compared with both Kaltostat and Sorbsan, are being
developed.
Alginates are not the dressing of choice for infected wounds and should not be applied to
dry or drying wounds. Most alginates require a secondary dressing.
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 Dressings containing an antimicrobial agent
An important consideration in the design of new dressings is their ability combat microbial
infection. Many dressings now exploit bioactive properties to promote healing and to control
infection. These dressings include the now well-known sustained-release iodine and silver
dressings (eg, lodosorb, Actisorb Silver 220). Silver metal and its salts have been used for
several generations under many different formulations (eg, ointments, pulvers, foams, films).
Possible reasons for the antimicrobial effect of silver include:
(1) interference with bacterial electron and ion transport;
(2) binding to bacterial DNA, which may impair cell replication;
(3) interaction with cell membrane, which may damage its structural and receptor function;
and
(4) formation of insoluble and metabolically ineffective compounds.
The ideal silver dressing will contain a concentration of silver to exert an effective
antibacterial effect without or with only limited systemic absorption. However, locally
applied silver compounds may react with wound fluid and form black silver
sulphide, giving the skin a gray discoloration. The use of silver nitrate solution is more
likely to cause this phenomenon than modern silver dressings.
One of the widely used silver dressings is Actisorb Plus, an activated charcoalcloth
impregnated with silver. It is reported to absorb bacteria, which are then inactivated by the
silver. Now marketed as Actisorb Silver 220, it is intended for use over partial- or full-
thickness wounds, such as pressure ulcers, venous ulcers, diabetic ulcers, and acute and
chronic wounds, and it is claimed to be the only dressing currently available in the United
States that "combines broad-spectrum antimicrobial action, bacterial toxin management and odor
control" (J+J news, March 2003).
Another new generation product, Acticoat, the silver antimicrobial barrier
dressing,consists of a rayon/polyester nonwoven core laminated (by sonic welds)
between an upper and lower layer of silver-coated, high-density polyethylene mesh
(HDPE).The laminations are held in place with ultrasound welds. The silver-coated HDPE
layers are designed to be barriers against microbial infection of a wound.
Acticoat is now available as both a nonabsorbable form and an absorbent
antimicrobial barrier dressing effective to bacterial penetration. In its absorbable
form, Acticoat is a calcium alginate dressing using novel silver- coating technologies in a

7
dressing designed to prevent wound adhesion, to control bacterial growth, and to facilitate
burn wound care.
The barrier functions of the dressing may help reduce infection in moderately-
to-heavily exuding partial- and full-thickness wounds, including decubitus ulcers, venous
stasis ulcers, surgical wounds, first- and second- degree burns, grafts, and donor sites. The
sustained-release of broad- spectrum ionic silver activity protects the dressing from bacterial
contamination, whereas the alginate absorbs excess wound fluid to form a gel that
maintains a moist environment for optimal wound healing.
In a new multilayer Acticoat (Acticoat-7), the silver antimicrobial barrier dressing
consists of 2 rayon/polyester nonwoven inner cores laminated (by sonic welds) between 3
layers of silver-coated HDPE. The laminations are held in place with ultrasound welds.
The silver-coated HDPE layers are designed to be barriers against microbial infection of
a wound. Such products can provide an effective antimicrobial barrier for up to 5- 7
days against 150 pathogens, including both methicillin- resistant Staphylococcus
aureus (MRSA) and vancomycin-resistant enterococci (VRE)
A number of controlled clinical studies have been performed to evaluate the safely and
the efficacy of Acticoat. In a matched-pair, randomized, prospective clinical study for the
treatment of burns, Acticoat was assessed for its ease of use, patient comfort, and
antimicrobial effectiveness compared with standard care in the same institution. In general,
the results were promising, with patients reporting less pain on removal with Acticoat and
nurses reporting no significant difference in ease of application. The frequency of
burn wound sepsis and the occurrence of secondary bacteriemia were both reduced.
A comprehensive laboratory study of the antimicrobial activity of Acticoat has also
been reported. In a number of tests, Acticoat demonstrated improved antimicrobial
performance over existing silver-based products. In addition to killing bacteria more
rapidly, it had the lowest minimum inhibitory concentration and minimum bactericidal
concentration. In a controlled study on donor site wounds, Allevyn showed significantly better
results than Acticoat with respect to time to healing and extent of reepithelialization. No
significant differences were seen in the incidence of bacterial cultures, and, while
scarring appeared initially worse with Acticoat, this resolved by 3 months. Overall, the
findings did not support the use of Acticoat for this application, although they did support
its continued use for burn sites.
Local collagen-based drug delivery systems

8
Recently, collagen-based dermal matrices (sponges or transparent, semipermeable
membranes) containing gentamicin have been successfully used for the treatment of infected
burn wounds and for the prevention of wound infection in large-surface wounds, including
severe burns. Such matrices (Sulmycin-Implant, Collatamp-G, INNOCOLL Inc, US) are
commercially available and are distributed by Schering-Plough, United States, in many
countries worldwide.
Wound coverage with allogenic cultured epidermal sheets
One of the drawbacks in the use of autbldgous cultured epithelial sheets for
coverage of deep and extensive wounds is the time required for the growth of
cells in vitro. In fact, recent clinical and experimental work demonstrated that
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.

Rama Three new codes have been established for surgical dressings: