Clinical Perspectives on the Use of Allograft Skin

© 2024 HMP Global. All Rights Reserved.

Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of ePlasty or HMP Global, their employees, and affiliates.

A 35-year-old male was admitted to the burn center after he threw gasoline onto a bonfire. On examination in the emergency department, he was found to have full-thickness burns on his anterior and posterior trunk, legs, and arms, accounting for 50% of his total body surface area. The patient was stable after resuscitation and on post-burn day 2 (PBD2), was taken to the operating room for excision and split-thickness autografting of his chest and arms. Two days later (PBD4), residual burn tissue was excised from his back. Due to the limited availability of donor sites, cryopreserved allograft was applied (Figure 1). The allograft had been stored at -80°C in the blood bank’s pathology freezer and was thawed using warm saline at 39°C before immediate transplantation onto the patient’s back. On PBD12, the allograft was removed revealing a noninfected wound bed with active bleeding. The wound was then resurfaced with 2:1 meshed split-thickness autograft reharvested from healed donor sites. Complete wound healing was achieved in 7 days.

Figure 1. Excised burn resurfaced with meshed cadaver allograft from 2 donors. 

Allografting, the transplantation of tissue between individuals of the same species, offers valuable benefits in wound healing. Cutaneous allograft suppresses microbial growth and proliferation and seals the wound. It reduces evaporative water loss and exudation of electrolytes and protein and prevents the ingress of bacteria. It creates a protected moist environment that promotes wound healing and can limit burn wound conversion. Once adherent, allograft alleviates pain, facilitating earlier mobility. The reduction of heat loss and pain also attenuates the hypermetabolic response in extensive burns, conserving energy resources. These positive effects are attributed to initial adherence, caused by the formation of a fibrin matrix followed by fibroblast proliferation and collagen synthesis, rendering graft viability less crucial.¹

The application of live allograft also provides superior outcomes through graft integration (“take”) where the epidermis survives anaerobically until vascularization occurs.² This process stimulates vascular ingrowth from the wound bed, priming the wound for subsequent autologous skin grafting. A satisfactory bed is indicated by its pink color, blanching, adherence of allograft to the wound bed, and brisk bleeding upon removal of the engrafted skin.

The utilization of allograft skin is a standard approach for the temporary resurfacing of excised burns when autologous tissue is unavailable. The technique allows the likelihood of “take” to the wound,enabling improvement of recipient bed quality and vascularity before autografting.³ Alexander et al described a technique for the treatment of large burns whereby widely meshed autograft is covered with sheet or narrowly meshed allograft. This strategy prevents desiccation of the interstices, protects fragile autografts, and facilitates epithelialization of the wound as the allograft is naturally rejected and shed (Figure 2).⁴ Moreover, the incorporation of allodermis into the wound may reduce scarring and the visibility of the mesh patterns. 

Figure 2. Meshed autograft (4:1) covered with allograft (2:1) is used to resurface an area of excised full-thickness burn. 

The use of abraded allograft as a substrate for cultured epithelial autograft (CEA) was described by Cuono⁵ to improve “take” and reduce the fragility of autologous cultured cells. Allodermis, due to lack of MHC class II expressing Langerhans cells, is relatively immunologically inert, allowing for “creeping substitution” by autologous tissue and rapid epithelialization. Allograft also serves as a temporary cover for extensive second-degree burns with the potential to heal, promoting more rapid healing times and facilitating nursing care.⁶ Similarly, patient discomfort associated with the treatment of extensive erosive cutaneous diseases, such as toxic epidermal necrolysis, can be minimized. 

In cases following the excision of full-thickness burns of the face, the application of allografts for 24 to 72 hours facilitates control of bleeding prior to definitive autografting, reducing the likelihood of scattered graft loss from hematomas and permitting reassessment of the adequacy of the initial excision (Figure 3). High-risk patients with sepsis presenting late after extensive burns may benefit from excision of all necrotic tissue and resurfacing with allograft to allow resuscitation, analysis of microbiological results, and commencement of systemic antibiotics (Figure 4).

Figures 3. (A) A 20-year-old female sustained deep facial burns in a house fire. (B) The face has been excised to healthy bleeding tissue. (C) The face is resurfaced with sheet allograft in aesthetic units. Meticulous attention to detail can affect the final appearance, despite the temporary status of the graft.

Figures 4. (A) An 8-year-old girl seen ventilated in an intensive care unit with deep infected burns caused while running through a rice field that ignited. (B) The lower extremities have been excised to the fascia and covered with 2:1 meshed allograft. The patient was weaned from the ventilator within 1 week.

Despite its advantages, allograft has certain limitations. The risk of disease transmission and T-cell-mediated immunological rejection pose significant concerns. Other constraints include the cost associated with procuring and storing the tissue and the limited availability of fresh allograft. While the rates of disease transmission are low, and rigorous screening measures have improved safety, isolated cases of bacterial and viral disease transmission, including HIV, Hepatitis C, and cytomegalovirus, have been reported.⁷ 

The expression of type II histocompatibility antigens initiates rejection in about 10 to 14 days in immunocompetent individuals,⁸ characterized by peeling of the skin, acute inflammatory reactions, and susceptibility to infection. Banks reported a case whereby the application of 1:1 meshed allograft to the abdomen of a 19-year-old man with a 75% flame burn produced stable permanent closure of the wound without hypertrophic scarring. Human leukocyte antigen (HLA) typing and histologic analysis, however, suggested that the mechanism of allograft persistence may be due to the repopulation of the allograft by recipient cells rather than the survival of donor cells.⁹ Various pharmacologic agents have been used to prolong skin allograft survival, such as azathioprine, antithymocyte globulin, steroids, and cyclosporine A,¹⁰ though prolonged immunosuppression is associated with life-long risks of infection and malignancy. Strategies to populate burn allografts with host endogenous stem cells to prolong graft survival are underway. Transplantation studies in rodent models have demonstrated that the C-X-C chemokine receptor type 4 (CXCR4) binding agent, AMD-3100, combined with sub-immunosuppressive doses of tacrolimus, worked synergistically to liberate essential stem cells from the bone marrow, rescuing grafts from rejection and producing a chimeric graft.¹¹

Allograft is supplied as fresh, cryopreserved, or glycerol-preserved. Fresh cadaver allograft is considered the best temporary skin substitute in terms of adherence, vascularization, and control of infection, but availability is limited. Viable skin can be retrieved for up to around 24 hours after death.¹² Harvested skin is folded in fine-meshed gauze and placed in a nutrient medium such as RPMI 1640, which is exchanged every 3 days and can be stored for 14 days refrigerated at 4°C. Reliable “take” has been demonstrated on nude mice for up to 20 days, though there is a sharp decline in viability reaching 50% of baseline from 5 to 15 days after harvests.¹

Cryopreserved allograft skin (CPA) provides a longer storage period and more time for microbiological assessment. It is stored in low-temperature freezers at -80°C or in liquid nitrogen at -196°C. The tissue is treated with a cryopreservation solution, typically 10% dimethyl sulfoxide (DMSO), and frozen at a controlled rate of about 1°C per minute to limit intracellular ice crystal formation and retain cell viability. Before application, the skin is rapidly thawed in 0.9% saline at 37ºC and rinsed thoroughly. CPA has been shown to retain up to 73.4% of its original viability¹³ and has an expiration date of 5 years.¹⁴

Glycerol-preserved allograft (GPA) is used primarily in Europe. It is stored in 85% glycerol at 4ºC, with an estimated storage life of about 2 years. The advantages of GPA include its antimicrobial properties and decreased immunogenicity. Although nonviable and non-vascularized, GPA effectively adheres to the wound, and the absence of viability does not appear to impair its function as a biological dressing.¹⁵