Long-Term Ex Vivo Human Skin Models for Burn Injury Research: A Scoping Review.

Abstract

Human burn wounds exhibit complex, depth-dependent healing processes that may extend beyond 21 days, underscoring the need for human-relevant long-term experimental models. Conventional in vitro systems, bio-engineered skin constructs and animal models fail to adequately reproduce the structural organization, depth-dependent injury patterns and temporal progression characteristic of human burn wounds. Ex vivo human skin explant models preserve native tissue architecture and therefore represent a promising translational alternative; however, their capacity to sustain long-term viability and regenerative responses remains insufficiently defined. This scoping review systematically mapped how thermally induced burn models using ex vivo human skin are designed, maintained and evaluated, with particular emphasis on factors enabling extended culture. The review was conducted in accordance with PRISMA-ScR guidelines. PubMed and Web of Science were searched for studies published between 2015 and 2025 describing thermally induced burns in ex vivo human skin explants. Eligible studies were descriptively charted focusing on burn induction methods, culture duration, tissue viability assessments, wound healing endpoints and model applications. Seven studies met the inclusion criteria, reporting culture durations ranging from 3 to 27 days. Sustained viability beyond 2 weeks was achieved using optimised strategies such as air-liquid interface culture and mechanical stabilisation. Burn depth emerged as the primary determinant of tissue survival and regenerative capacity, with re-epithelialization observed only in superficial or partial-thickness burns under extended culture conditions. These findings highlight both the translational potential and the need for methodological standardisation of long-term ex vivo human burn models.