We read with great interest the article by Fonseca and colleagues describing the establishment of a living-donor skin-banking workflow and the clinical application of cryopreserved total skin allografts (CTSA) for complex wound management 1. The authors are to be commended for proposing a pragmatic and potentially scalable approach that repurposes tissue otherwise discarded after body-contouring procedures while reporting substantial operational experience and an early clinical series spanning heterogeneous, high-burden wound etiologies. Notably, their observation of consistent initial graft take followed by a predictable superficial eschar phase with an apparently vascularized underlying “neodermis” is intriguing and highlights CTSA's potential role as a biologically active bridge to definitive closure and reconstruction. At the same time, several points warrant clarification and could further strengthen the translational impact of this work. The manuscript outlines a processing pathway that includes cryopreservation and (after negative testing) terminal irradiation. Because “viable” skin allografts and “non-viable but structurally preserved” allografts are expected to differ in immunogenicity, growth factor activity, and integration, it would be helpful if the authors more explicitly defined the intended biological state of CTSA at implantation (e.g., viability thresholds for keratinocytes/fibroblasts, metabolic assays, and histologic markers). Classic guidance in skin banking emphasises that viability-preserving approaches generally cannot employ conventional terminal sterilisation, whereas non-viable grafts can be terminally sterilised and still provide important barrier and scaffold functions. In this context, additional details regarding the irradiation step (dose verification, temperature conditions, packaging geometry, and validation strategy) and its anticipated effects on cellular survival and extracellular matrix integrity would be valuable. Prior work suggests that irradiation conditions and cryoprotectant concentrations can materially affect cytotoxicity and tissue structure, which could directly inform the mechanistic positioning of CTSA (regenerative living tissue versus bioactive scaffold) 2. The reported discard rate—predominantly due to storage/cold-chain failures and, to a lesser extent, pathogenic contamination—provides a transparent and practically important view into real-world implementation. This is precisely where other programs may learn the most. We encourage the authors to expand on: (1) the microbiology profile (organisms detected, the sampling stage at which they were identified, and frequency); (2) decontamination methods (antibiotic/antimycotic composition, incubation conditions, and acceptance criteria); and (3) the corrective and preventive actions implemented after the storage failure event (redundant monitoring, alarm escalation pathways, backup power validation, temperature mapping, and release governance) 3. Established frameworks for microbiological screening and process validation could also be referenced as explicit comparators to enhance reproducibility across centers. The clinical experience is promising but necessarily limited by small numbers, heterogeneity of wound types, and disrupted follow-up. Future iterations would benefit from standardised reporting of clinically meaningful endpoints—such as time to definitive closure, infection recurrence, pain scores and analgesic requirements, number of re-operations, quantitative graft-take assessment, scar quality, and functional outcomes—ideally with prespecified time points. Additionally, positioning CTSA relative to available biologics (e.g., viable cryopreserved split-thickness allografts used in diabetic foot ulcers and other chronic wounds) 4 and dermal templates would clarify where CTSA provides the greatest marginal value, particularly in resource-limited settings where logistics and cost-effectiveness are decisive. The observed timing of the superficial eschar/rejection phase is consistent with the known immunobiology of skin allografts 5, yet the reported “neodermis-like” layer suggests a potentially constructive host remodelling response. Mechanistic clarification—such as determining the donor-versus-recipient cellular origin of the newly formed dermal-like tissue (e.g., sex-mismatched tracing, donor-specific genotyping, or immunohistochemistry) and documenting sensitization risk in recipients (e.g., anti-HLA antibody development in patients undergoing repeated applications) 6—would substantially strengthen the proposition that CTSA functions as a regenerative platform. This is particularly relevant if repeated CTSA use is anticipated for chronic wounds or staged reconstruction, where sensitization may have downstream implications. In summary, Fonseca et al. present an innovative and operationally detailed contribution that may broaden access to biologic wound coverage and introduce a novel staged pathway toward durable closure. Addressing the points above—particularly around product viability/sterility characterization, microbiological governance, standardized outcomes, and immunologic/mechanistic validation—could accelerate adoption and facilitate multicenter replication. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Ma et al. (Sun,) studied this question.