Forty Years Later-Complications and Mortality Associated with Cultured Epithelial Autografts in Burn Patients: A Systematic Review.
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Cultured epithelial autografts (CEAs) have been used for more than 40 years in the setting of extensive total body surface area (TBSA) burns. The development and clinical implementation of cultured epidermal autografts and, subsequently, combined cultured dermo-epidermal autografts (CDEAs) have provided an essential adjunctive treatment option. Over the past five decades, numerous studies have reported on their clinical application. CEAs are manufactured from autologous epidermal cells that are expanded in vitro and assembled into sheet grafts suitable for transplantation. While substantial literature exists regarding their clinical use, data specifically addressing treatment-related complications remain scarce. This systematic review aims to comprehensively synthesize the available evidence on sheet-type CEA/CDEA use in burn patients, with a particular focus on complications, tumorigenicity, and mortality. A systematic literature search was conducted in 2023 across five electronic databases (Cochrane on 31 May 2023, Embase on 31 May 2023, Ovid Medline on 31 May 2023, Scopus on 1 June 2023, and Web of Science on 1 June 2023) to identify studies reporting on the use of CEAs in burn patients. Search terms included combinations of "cultured," "epithelial," "autografts," "take rate," "mortality," and "skin cancer." Eligible studies were human clinical studies involving burn patients treated with sheet-type CEA or CDEA, published in English, French, or German. Exclusion criteria comprised studies involving allogeneic materials, in vitro or animal studies, and commentaries and editorials. Efficacy endpoints included complications, tumorigenicity, and mortality outcomes in CEA-treated patients. Risk of bias was assessed for each included study using the modified Downs and Black checklist and graded according to Hooper et al. Seventy studies contributing 72 patient cohorts published between 1984 and 2023 met inclusion criteria, encompassing a total of 2091 patients from all five continents. The mean graft take rate was 64% in adults and 70% in pediatric patients. Complication events and mortality data are described in the corresponding tables. This systematic review represents the first comprehensive synthesis specifically addressing complications, tumorigenicity, and mortality in burn patients treated with CEAs. The reported adverse events must be interpreted within the context of the high morbidity associated with extensive burn injuries. The observed mortality and number of complications appear primarily related to burn severity rather than to CEA use itself. No adverse events were identified that could be specifically attributed to CEAs. Interpretation of these findings is limited by the clinical and methodological heterogeneity of the included studies. In patients with extensive burn injuries, the use of CEAs is associated with a relatively low number of complications and appears to be a safe and clinically justified treatment option. This study received no internal or external funding. This study is referenced in the PROSPERO Database for systematic reviews under the number CRD420251040971.