Allografts

Cadaveric allograft skin has always been the temporary coverage of choice. Despite the potential infection risks that come with its use and its high cost, it has gained popularity given its ability to take as an allograft and provide durable coverage for an extended period of time (compared with other temporary dressings), providing wound coverage for 3 to 4 weeks. Refrigerated allograft remains viable for up to 14 days when preserved in adequate nutrient media (RPMI [Roswell Park Memorial Institute]-1640). Cryopreserved allograft can be stored for a longer period of time and retain good viability. It has an indefinite shelf life and can be accumulated for future use. It is usually prepared by controlled-rate freezing in cryopreservation solution. Despite the conditions of storage, cryopreservation itself does not eliminate the risk of viral or bacterial transmission. However, most cryopreserved allografts are processed and stored on an elective basis, which gives time for cautious and adequate donor screening for potential pathogens. Human immunodeficiency virus and hepatitis C were cited as causes in the past, but tighter US Food and Drug Administration (FDA) regulations and extensive tissue donor screening have limited such occurrences.

Another limiting factor is the availability of allografts. Fresh allografts usually need to be used within a few days to a week at most or otherwise have to be cryopreserved. The careful selection of donors further compromises availability because patients with systemic malignancy, sepsis, and viral illnesses need to be excluded. Cost should also be taken into consideration because fresh allografts cost up to $2.65/cm ² whereas the price for cryopreserved allograft is $2.15/cm ² (quote from Allosource, Centennial, CO). The development of tissue banks providing high-quality, safe, and viable allografts has contributed to the increased cost of this coverage option.

Xenografts

Over the years, skin from multiple animal species has been used as temporary coverage. In the late nineteenth century, the first xenograft to be used in the United States was harvested from sheep. Frog skin has also been used in some instances, but the only commercially available products to date are taken from pigs. However, given the high potential for antigenicity, there needs to be a careful preparation process. Several methods have been used, including silver impregnation, irradiation, and freezing and thawing. Xenografts can provide temporary coverage when allografts are unavailable or cost-prohibitive. Because of its inability to revascularize fully, they should be viewed more as a dressing than as a true skin substitute. Xenografts have been shown to retard evaporative water loss, reduce infection, and encourage autologous epidermal growth. Most clinicians have used xenografts as dressings for covering partial-thickness burns, donor sites, and wounds in toxic epidermal necrolysis. Advantages of xenografts include lower cost, prolonged shelf life, and availability. Disadvantages include the potential for transmission of infectious agents in addition to some cultural and religious considerations.

Amnion

Temporary wound coverage with inner amnion and outer chorion has been described for many years. Outer chorion carries the disadvantage of a higher antigenic potential; hence amnion has gained more popularity. The main use of amnion is for ophthalmologic (corneal) burns. Multiple commercial products have been made available in the past few years (eg, AmnioGraft, Bio-Tissue, Doral, FL; AmnioGuard, Bio-Tissue, Doral, FL; Acelagraft; Celgene Cellular Therapeutics, Cedar Knolls, NJ) and have been used as overlay after autografting or as a dressing in superficial and mid-dermal burns. Amnion has also been used in small areas, such as the diabetic foot. Advantages of amnion include that it is available, readily adherent, transparent (thus allowing wound monitoring), has the potential to reduce the risk of wound infection, and may have an analgesic effect. Disadvantages include difficulty in handling and fast degradation, in addition to the lack of adherence in full-thickness burns, making it a temporary dressing for such wounds.

Other Temporary Dressings

Acticoat (Smith & Nephew Inc, Andover, MA) is a silver antimicrobial dressing containing nanocrystalline silver that offers a slow release of silver ions over time. It is indicated in both full-thickness and partial-thickness wounds. It has broad antimicrobial coverage, but it has to be changed every 2 to 4 days. Silver-impregnated temporary dressings have been shown to reduce healing time and pain.

Aquacel Ag (ConvaTec, Princeton, NJ) is a hydrofiber dressing with silver. It has been useful in treating second-degree burns, chronic wounds, and donor sites. Aquacel maintains a moist wound environment by controlling exudate and hence reduces the likelihood of infection. It has also shown to improve wound healing time and to be superior to silver sulfadiazine.

Biobrane (Smith & Nephew Inc, Andover, MA) is another temporary burn wound coverage alternative consisting of a woven nylon membrane coated with silicone to which collagen is chemically bound. Like Acticoat and Aquacel, it has been shown to be as effective as topical silver sulfadiazine in reducing pain and decreasing wound healing time. The main advantage of Biobrane remains in its cost-effectiveness because it has the potential to remain in place for a prolonged period of time if the wound is clean. It can adhere firmly in superficial partial-thickness burns until healing occurs, and this is how most clinicians have used this dressing. However, it is susceptible to infection and episodes of life-threatening toxic shock syndrome have been reported.

Although no longer produced, TransCyte (Advanced BioHealing, Westport, CT, USA) is similar to Biobrane and composed of a nylon mesh covered with fibroblasts from neonatal human foreskin. It was previously suggested as a temporary coverage for wounds waiting to be covered with autografts. One postulated mechanism is that the harvested fibroblasts secrete extracellular matrix components and growth factors that contribute to the healing process.

Apligraf (Orthogenesis Inc, Canton, MA) is made from neonatal foreskin fibroblasts and keratinocytes (dermal components from cultured fibroblasts with bovine type I collagen and cultured keratinocytes eventually added to form a stratum corneum). Apligraf is currently FDA approved for use in treating diabetic foot and venous ulcers although it is also used in burn treatment. Cost is a significant concern and has prevented its use for larger wounds.

Like TransCyte, OrCel (OrCel International Inc, New York, NY) is no longer available. OrCel is an allogeneic, bilayered substitute composed of cultured human fibroblasts and keratinocytes. However, the fibroblasts in OrCel are seeded onto a preformed matrix instead of being cocultured with collagen in solution. Also, OrCel lacks Apligraf’s stratum corneum. OrCel is FDA approved for use on split-thickness skin graft donor sites in patients with burns and in reconstructive hand surgery in patients with epidermolysis bullosa. A study performed by Still and colleagues found OrCel to be more effective than Biobrane with regard to wound closure time and scar appearance.

Cultured Epidermal Autografts

Cultured epidermal autografts (CEAs) are an available approach for wound coverage. These skin grafts are grown in a laboratory after obtaining a biopsy from the patient’s own skin and several weeks later the grafts are applied to the wound bed. Most clinicians reserve the use of CEA for extensive burn injuries when there is very little donor site remaining. This approach is extremely costly, and there are disadvantages to CEAs, chiefly related to the thin and fragile nature of these grafts. Graft take is highly susceptible to shear forces, and once the grafts have taken they remain fragile and prone to injury for a prolonged period of time compared with standard STSGs.

Epicel (Genzyme Biosurgery, Cambridge, MA) is the best known commercially available CEA system on the market. The grafts are produced by obtaining a patient’s own keratinocytes from a full-thickness skin biopsy, treating them with trypsin, and expanding them ex vivo in coculture with murine 3T3 fibroblast feeder cells. The medium also contains fetal calf serum, insulin, transferrin, hydrocortisone, epidermal growth factor, and cholera toxin. As a result, a neoepidermis made of keratinocyte layers of variable thickness is arranged into sheets. Its use has been reserved for patients with large surface area burns (>30%), especially when donor availability is severely diminished or absent. Various studies have shown different rates of graft take for Epicel. Williamson and colleagues studied 28 patients with a mean total body surface area burned of 52.2% and a mean total full-thickness injury of 42.4% treated with Epicel over a mean period of 5 years. Mean take rate was 26.9% of the grafted area. Despite the hope for durable wound coverage, many complications of CEA have been reported. Blistering and shearing caused by the thin layer of graft in addition to contractures and pruritus remain an issue. Long in-vitro expansion times, high cost, susceptibility to infection, and prolonged hospital stays have all rendered it a last-resort option when other alternatives are not applicable.