Skin allograft

A skin allograft is skin transplanted from a human donor (most often a deceased donor) to a recipient who is genetically distinct from that donor, in contrast to an autograft, which is skin moved from one site to another on the same person. [1][2] In burn and wound care its most established role is as a temporary biological dressing: donor skin is placed over an excised burn or large open wound to restore barrier function, reduce loss of fluid and protein, and limit infection while the wound bed is prepared, after which it is rejected by the recipient's immune system and replaced by the patient's own skin (autograft) or other definitive coverage. [1][3][4] Because allograft skin is foreign tissue, it is generally not a permanent solution. [5][6]

Skin allograft is also called cadaver skin, allogeneic skin, or homograft. [1] It is recovered, processed, and distributed by tissue banks under U.S. federal regulation and voluntary accreditation standards, and donor skin is also the starting material for acellular dermal matrices used in reconstructive surgery. [7][8]

Clinical use as a temporary wound cover

The principal use of skin allograft is to provide temporary coverage of extensive burns and other large wounds when the patient does not have enough uninjured skin available for immediate autografting. [1][3] After a deep burn is surgically excised, the open wound bed loses the protective functions of intact skin. Allograft skin applied to that bed acts as a biological dressing that protects against desiccation and contamination, reduces wound pain, decreases evaporative loss of fluid and protein, and limits bacterial colonization while the wound matures. [1][4]

A distinctive feature of skin allograft, compared with synthetic dressings, is that viable allograft can vascularize, or "take," on a healthy wound bed. [1] When allograft shows general adherence and evidence of graft vascularization within roughly 48 to 72 hours of application, clinicians can anticipate that autograft skin later applied to that same bed will also take well; in this way allograft is used both to cover the wound and to test whether the bed is ready for definitive grafting. [1] Allograft is also used to overlay widely meshed autograft, protecting the interstices of the autograft mesh until the patient's own skin closes the gaps. [3]

Rejection and the contrast with autograft

Skin allograft is immunologically recognized as foreign and is rejected by the recipient over a period of roughly one to three weeks if it is not first removed and replaced. [5][9] Studies of burn patients indicate that, absent replacement by autograft, allograft rejection is likely to occur within about two weeks. [5] Because of this, allograft is regarded as temporary coverage rather than permanent wound closure. [3][6]

The immune response is driven mainly by the epidermal component of the graft. Rejection of skin allograft is mediated largely by donor major histocompatibility complex (MHC) class II expressing Langerhans cells in the allograft epidermis, which are present in the epidermis but largely absent from the dermis; this helps explain why allograft dermis provokes a weaker rejection response than allograft epidermis. [9] Some reports describe occasional prolonged survival of allograft in deep wounds, but durable persistence is the exception rather than the rule. [6] General principles of graft rejection are discussed in transplant immunology.

The definitive contrast is the autograft. A split-thickness or full-thickness autograft, taken from the patient's own uninjured skin, is not rejected and provides permanent coverage; autograft remains the gold standard for wound closure in burns. [10] When a patient lacks enough donor sites, cultured epithelial autograft (CEA), in which a small skin biopsy is expanded in the laboratory into sheets of the patient's own keratinocytes, can provide permanent epidermal coverage, though it typically requires roughly two to three weeks of culture before the grafts are ready. [9] In some protocols, cryopreserved acellular allograft dermis is used as a durable dermal substrate onto which cultured autologous keratinocytes are applied, combining donor-derived dermal scaffold with the patient's own permanent epidermis. [9]

Recovery, processing, and preservation

Skin for allograft is recovered from consented deceased donors by tissue banks, typically as split-thickness sheets harvested with a dermatome from areas such as the back and legs. [11] The recovered tissue is then processed and preserved by one of several methods, which differ in whether the cells remain viable. [12]

• Fresh and refrigerated allograft retains living cells but has a limited working life; stored at about 4 degrees Celsius, fresh allograft has an effective shelf life of only about seven to ten days, and it requires refrigerated storage and a steady donor supply. [1]
• Cryopreserved allograft is frozen with cryoprotectants for long-term storage and retains partial cell viability after thawing; reported keratinocyte viability is lower than fresh skin but higher than glycerol-preserved skin (one comparison reported roughly 21 percent viability for cryopreserved skin, about 9 percent for glycerol-preserved skin, and about 59 percent for fresh skin). [12]
• Glycerol-preserved allograft is treated with high concentrations of glycerol, which renders the tissue non-viable while preserving its structural and mechanical properties; glycerol also has antimicrobial effects and allows storage without freezing. [12][13]
• Decellularized (acellular) allograft has its cellular components removed, leaving an extracellular-matrix scaffold (see below). [8]

Preservation method affects clinical behavior. Partly viable cryopreserved allograft tends to produce better granulation of the wound bed than non-viable glycerol-preserved skin, while glycerol preservation offers logistic and antimicrobial advantages and maintains tissue structure. [12][13] Reviews of skin banking note that both cryopreserved and glycerol-preserved allografts are among the most widely used forms of temporary biological coverage for severe burns, and that no single method is universally superior. [13]

Acellular dermal matrices derived from donor skin

Donor skin is also the source material for acellular dermal matrices (ADMs). These products are made by decellularizing human cadaveric dermis with detergents or other agents to remove epidermal and dermal cells and antigens while preserving the dermal extracellular matrix, including collagen, elastin, and associated proteins. [8] Removing the cellular and antigenic components is intended to reduce the risk of rejection and inflammation, allowing the matrix to be incorporated by the recipient's tissue. [8] AlloDerm, introduced as an early human ADM, is one widely cited example, and such matrices are used in burn reconstruction, abdominal-wall and breast reconstruction, and other soft-tissue procedures. [8] This article mentions ADMs only to situate them relative to skin allograft; their reconstructive uses are a distinct topic.

Donor screening and regulation

In the United States, human skin allograft is a human cell, tissue, or cellular and tissue-based product (HCT/P) and is recovered and processed by tissue banks that must follow U.S. Food and Drug Administration (FDA) regulations and, for accredited banks, the standards of the American Association of Tissue Banks (AATB; now operating as the Association for Advancing Tissue and Biologics). [7] Conventional skin allograft that is minimally manipulated and intended for homologous use is generally regulated solely under section 361 of the Public Health Service Act and the regulations in 21 CFR Part 1271, rather than as a licensed biologic or drug. [14] Part 1271 establishes donor-eligibility, current good tissue practice, and other requirements for HCT/Ps; for the regulatory framework, see FDA regulation of human tissue (HCT/Ps). [14]

Donor screening is central to allograft safety. Prospective skin donors are screened through medical and social history and serologic and other testing for transmissible diseases. Reported screening includes testing for HIV-1 and HIV-2, hepatitis B, hepatitis C, human T-cell lymphotropic virus, and syphilis, among other infectious agents. [1] AATB standards and FDA donor-eligibility rules together specify the combination of disease states screened for and the tissue-handling, processing, and storage controls that recovering establishments must follow; AATB updated its donor-screening requirements effective in 2023 to strengthen tissue safety. [7][15]

Mass-casualty preparedness and skin-bank supply

Because deep burns over large body areas can require substantial quantities of temporary coverage, allograft skin is treated as a strategic resource for mass-casualty burn events such as fires, explosions, and chemical, radiological, or nuclear incidents. [16] Analyses of U.S. supply have noted that the allograft-skin supply chain is variable and prone to fluctuation because it depends on donor availability, relationships between organ procurement organizations and treatment centers, and inventory management, and that consolidation among tissue banks has shifted what was historically a local resource toward a smaller number of national suppliers. [16][17]

In response, the U.S. Biomedical Advanced Research and Development Authority (BARDA) has funded vendor-managed inventories of cryopreserved skin allograft for emergency preparedness; in 2022 BARDA awarded contracts to tissue banks to build and maintain such inventories for use in mass-casualty burn emergencies. [16] The broader donation system that supplies this tissue, alongside organ recovery, is described in organ donation.

Ethics and consent

Skin recovery for allograft, like other deceased tissue donation, requires authorization. In the U.S. donation model, recovery proceeds only with prior donor registration or authorization from the legal next of kin. [18] Skin donation can raise distinct family concerns compared with internal-organ donation, because recovery affects the visible body. Studies of family decision-making report that concern about disfigurement or mutilation of the deceased's body is a frequently cited reason for refusing or limiting tissue donation, and that the prospect of skin removal can be experienced by families as a threat to the dignity or image of the deceased. [19] Research also finds that families who consent and families who refuse can both hold mixed positive and negative views of tissue recovery, complicating simple assumptions about donor families. [19] These findings inform how procurement organizations approach consent conversations and how recovery is performed to respect the donor's body. [18][19]

History

The use of skin from one person to treat the wounds of another has a long history in burn and reconstructive surgery. Free skin grafting was demonstrated in 1869 by the Swiss surgeon Jacques-Louis Reverdin, whose "pinch graft" technique transplanted small epidermal fragments onto wounds; in 1870 Georg David Pollock performed a successful pinch graft in a burn patient. [20] Reverdin is also credited with early attempts at using skin from one person to treat another's burns, but such allogeneic grafts were gradually destroyed rather than permanently incorporated, an early observation of rejection. [20] The first reported use of cadaveric skin to cover a burn wound dates to 1881. [20]

A scientific understanding of why allografts fail developed in the twentieth century. Before World War II, the American surgeon James Barrett Brown (1899-1971) postulated that homograft rejection resulted from genetic disparity between donor and host, anticipating later transplant immunology and the modern view of allograft skin as temporary, immunologically rejected coverage. [21] These insights, together with the development of skin banking and preservation methods, established the present role of skin allograft as a temporary biological dressing bridging severe burns to definitive autograft closure. [13][21]

See also

• Tissue bank
• FDA regulation of human tissue (HCT/Ps)
• Transplant immunology
• Organ donation

References

• Vyas KS, et al. "Human Skin Allograft: Is it a Viable Option in Management of Burn Patients?" PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC6676815/
• "Skin Allograft - an overview." ScienceDirect Topics. https://www.sciencedirect.com/topics/nursing-and-health-professions/skin-allograft
• "The Impact Of Human Skin Allograft As A Temporary Substitute For Early Coverage Of Major Burn Wounds On Clinical Outcomes And Mortality." PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC8126363/
• "The use of human deceased donor skin allograft in burn care." PubMed. https://pubmed.ncbi.nlm.nih.gov/20077178/
• "Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study." PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC5339616/
• "Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study" (permanence discussion). PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC5339616/
• "AATB Response to CDC Report: Strengthening Donor Screening for Tissue Allograft Safety." Association for Advancing Tissue and Biologics. https://www.aatb.org/news/aatb-response-cdc-report-strengthening-donor-screening-tissue-allograft-safety
• "Acellular Dermal Matrix in Plastic and Reconstructive Surgery." PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC9854008/
• Rotman S, et al. "Nonvascularized human skin chronic allograft rejection." American Journal of Transplantation. https://www.amjtransplant.org/article/S1600-6135(22)09311-X/fulltext
• "A Study of Cadaveric Skin Graft Harvest and Usage: An Observational Prospective Pilot Study." PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC11495681/
• "Cadaveric Skin - an overview." ScienceDirect Topics. https://www.sciencedirect.com/topics/engineering/cadaveric-skin
• "Comparison between cryopreserved and glycerol-preserved allografts in a partial-thickness porcine wound model." PubMed. https://pubmed.ncbi.nlm.nih.gov/26150190/
• "Current insights into skin banking: storage, preservation and clinical use." Biologics: Targets and Therapy (Dove Medical Press). https://www.dovepress.com/current-insights-into-skin-banking-storage-preservation-and-clinical-i-peer-reviewed-fulltext-article-BSAM
• "Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use." FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-considerations-human-cells-tissues-and-cellular-and-tissue-based-products-minimal
• "American Association of Tissue Banks Standards for Tissue Banking." AATB. https://a498c38321542e3afc7a-6340203f328f3cd60aa87439c450317d.ssl.cf2.rackcdn.com/aatb_22c51a909c525ed6c3d26b2b9ccbff84.pdf
• "AlloSource Announces Award from the U.S. Government to Supply Allograft Skin for Crisis Preparedness in the Event Of Mass Casualty Burn Incidents." AlloSource. https://allosource.org/allosource-announces-award-from-the-u-s-government-to-supply-allograft-skin-for-crisis-preparedness-in-the-event-of-mass-casualty-burn-incidents/
• "The availability of allograft skin for large scale medical emergencies in the United States." Cell and Tissue Banking. https://link.springer.com/article/10.1007/s10561-013-9367-z
• "Ethics of deceased organ donor recovery." HRSA. https://www.hrsa.gov/optn/professionals/resources/ethical-considerations/ethics-of-deceased-organ-donor-recovery
• "Family refusal of skin donation for transplantation: trends and associated factors." PMC. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290726/
• "Historical Evolution of Skin Grafting: A Journey through Time." PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC8066645/
• "A Short History of Skin Grafting in Burns: From the Gold Standard of Autologous Skin Grafting to the Possibilities of Allogeneic Skin Grafting with Immunomodulatory Approaches." PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC7998351/