Skin banking and allograft

Overview

Cadaveric skin allograft has served as the gold standard temporary biologic wound coverage for excised burn wounds for over five decades ^[1]. When a patient with a large burn has insufficient unburned donor sites for immediate autografting, allograft provides physiologic wound closure that reduces evaporative water loss, decreases bacterial colonization, diminishes pain, and prepares the wound bed for subsequent autograft application ^[2].

Skin banks are the infrastructure that makes allograft available. These tissue banking organizations procure skin from deceased donors, process it under controlled conditions, perform screening for infectious diseases, preserve the tissue using cryopreservation or glycerol treatment, and distribute it to burn centers on demand ^[3]. The availability, quality, and preservation method of allograft skin directly affect clinical outcomes.

Preservation methods

Cryopreservation

Cryopreserved allograft is stored at -70C to -196C (liquid nitrogen) with cryoprotective agents (typically glycerol or dimethyl sulfoxide) to maintain cell viability. Viable cryopreserved skin retains living fibroblasts and keratinocytes, vascularizes more rapidly after application, and provides temporary physiologic wound closure for 10-21 days before immune-mediated rejection occurs [1, 4].

The primary advantage of cryopreservation is that living cells produce growth factors and cytokines that actively promote wound healing. The disadvantages include higher cost, limited shelf life (typically 5 years at -70C), requirement for controlled-rate freezing equipment, and the theoretical risk of disease transmission from viable cells ^[3].

Glycerol preservation

Glycerol-preserved allograft is treated with 85% glycerol, which kills all cells while preserving the structural matrix of the skin. Richters et al. demonstrated that glycerol treatment maintains the fundamental structural integrity of the skin, including intact keratinocytes and Langerhans cells with Birbeck granules, but all cells are non-viable ^[5]. The immunogenicity of glycerol-treated skin is substantially reduced; T cells do not proliferate in response to glycerol-treated allogeneic cells, and graft loss is mediated by an inflammatory process (monocyte infiltration) rather than classical T-cell rejection ^[6].

Glycerol preservation offers practical advantages: room-temperature or refrigerated storage, longer shelf life, lower cost, inherent virucidal and bactericidal properties of glycerol, and easier logistics for distribution ^[3]. Clinical practice with glycerol-preserved allograft in a burn center showed no adverse effects, though it slightly increased the number of operative procedures ^[3].

Skin banking operations

Procurement

Skin is procured from deceased donors after consent from next of kin and serological screening for HIV, hepatitis B and C, syphilis, and other transmissible infections. Procurement typically occurs within 24 hours of death. Split-thickness skin (0.012-0.015 inch) is harvested using a powered dermatome from the back, thighs, and legs ^[2].

Processing and quality control

Procured skin undergoes microbiologic cultures, is trimmed and laid on backing material, and is processed according to the preservation method. Quality control measures include sterility testing, measurement of residual antibiotics if applicable, and documentation of donor screening results ^[2].

Distribution

Skin banks maintain inventories and distribute allograft to requesting burn centers. Supply is inherently variable and depends on organ and tissue donation rates. Shortages are common, particularly in regions with high burn incidence relative to donor population, and constitute a major limitation of allograft-dependent wound management strategies ^[7].

Clinical applications

Temporary coverage of excised burns

The primary indication for allograft is temporary closure of freshly excised full-thickness burns when autograft donor sites are exhausted or healing. Allograft adheres to the excised wound bed, vascularizes within 48-72 hours (cryopreserved), and maintains wound closure for approximately 2-3 weeks until immune rejection causes graft loss. At that point, donor sites have typically healed sufficiently for re-harvesting [1, 2].

Purdue et al. demonstrated in a multicenter trial that Biobrane (a biosynthetic alternative) was equivalent to frozen cadaver allograft for temporary coverage of excised full-thickness burns, with no significant difference in dressing changes, purulence, autograft take, or final results ^[1]. This established that synthetic alternatives can match allograft performance for specific indications.

Wound bed testing

Allograft can serve as a "test graft" to assess wound bed viability before committing autograft. A wound bed that supports allograft vascularization will support autograft take. This is particularly useful for wounds of uncertain viability, such as those over granulation tissue of questionable quality ^[2].

Micrograft carrier

Chong et al. described a technique using allograft sheets as carriers for autologous micrografts in a single-stage procedure ^[8]. Micrografts were laid 1 cm apart onto allograft sheets, creating a 1:9 expansion ratio. The allograft provides temporary wound closure while the micrografts proliferate and coalesce, eventually replacing the allograft as it is rejected.

Beyond burn care

Allograft has been applied to chronic ulcers, diabetic foot ulcers, necrotizing fasciitis, and acute traumatic wounds. A retrospective review from a Taiwanese center found that all wound types exhibited good wound bed preparation after allograft application and could be resurfaced with subsequent autograft ^[9].

Complications

Allograft-specific complications include immune-mediated rejection (inevitable with cryopreserved allograft; a feature, not a complication, as the allograft is intended as temporary), disease transmission (exceedingly rare with modern screening), and bacterial contamination of the allograft itself ^[2]. Sensitization of the recipient to alloantigens is a theoretical concern, but serial allograft application does not appear to preclude subsequent autograft take ^[10].

Special Considerations

Allograft availability varies globally. Many developing countries lack established skin banking infrastructure, driving interest in xenograft and synthetic alternatives ^[7]. Even in countries with established skin banks, supply fluctuations create periodic shortages that force centers to use alternative coverage strategies.

Religious and cultural considerations may affect acceptance of cadaveric tissue by some patient populations. Glycerol-preserved allograft, in which all cells are non-viable, may be more acceptable to some patients and families than cryopreserved (viable) tissue, though institutional ethics consultation is appropriate in such cases ^[3].

NovoSorb BTM has emerged as a synthetic alternative to allograft for temporising full-thickness wound coverage, with comparable clinical outcomes and the advantage of unlimited supply and consistent quality ^[11].

Controversies and Evidence Gaps

The relative merits of cryopreserved versus glycerol-preserved allograft for specific clinical scenarios lack high-quality comparative data. Institutional preferences are driven by local skin bank capabilities rather than evidence-based selection ^[3].

The future of allograft in burn care is uncertain as synthetic and engineered alternatives improve. Dermal regeneration templates, biosynthetic dressings, and autologous cell harvesting technologies all reduce dependence on cadaveric tissue, and whether allograft will remain the gold standard for temporary wound coverage is debated ^[12].

Standardization of skin banking practices across institutions and countries is incomplete, leading to variability in product quality and availability ^[7].

The immunologic consequences of serial allograft application, including potential sensitization that could affect future organ transplantation, have not been comprehensively studied in the modern era of tissue banking ^[10].

References

[1] Purdue GF et al. (1987). Biosynthetic skin substitute versus frozen human cadaver allograft for temporary coverage of excised burn wounds. J Trauma. 27(2):155-7. PMID: 3546711 [2] Saffle JR (2009). Closure of the excised burn wound: temporary skin substitutes. Clin Plast Surg. 36(4):627-41. PMID: 19793557 [3] Blome-Eberwein S et al. (2002). Clinical practice of glycerol preserved allograft skin coverage. Burns. 28 Suppl 1:S10-12. PMID: 12237057 [4] Purdue GF et al. (1997). A multicenter clinical trial of a biosynthetic skin replacement, Dermagraft-TC, compared with cryopreserved human cadaver skin for temporary coverage of excised burn wounds. J Burn Care Rehabil. 18(1 Pt 1):52-7. PMID: 9063788 [5] Richters CD et al. (1996). Morphology of glycerol-preserved human cadaver skin. Burns. 22(2):113-6. PMID: 8634116 [6] Richters CD et al. (1997). Immunogenicity of glycerol-preserved human cadaver skin in vitro. J Burn Care Rehabil. 18(3):228-33. PMID: 9169946 [7] May SR (1991). The effects of biological wound dressings on the healing process. Clin Mater. 8(3-4):243-9. PMID: 10149129 [8] Chong SJ et al. (2017). Technical tips to enhance micrografting results in burn surgery. Burns. 43(5):983-986. PMID: 28442165 [9] Tzeng YS et al. (2012). Clinical experience using cadaveric skin for wound closure in Taiwan. Wounds. 24(10):293-8. PMID: 25876054 [10] Albritton A et al. (2014). Lack of cross-sensitization between GalT-KO porcine and allogeneic skin grafts permits serial grafting. Transplantation. 97(12):1209-15. PMID: 24798308 [11] Betar N et al. (2023). Clinical outcomes and resource utilisation in patients with major burns treated with NovoSorb BTM. Burns. 49(7):1663-1669. PMID: 37344307 [12] Chogan F et al. (2023). Skin tissue engineering advances in burns. J Burn Care Res. 44(Suppl 1):S1-S4. PMID: 36567473 [13] Hansbrough JF et al. (1997). Clinical trials of a biosynthetic temporary skin replacement, Dermagraft-TC, compared with cryopreserved human cadaver skin. J Burn Care Rehabil. 18(1 Pt 1):43-51. PMID: 9063787