Automation-assisted human skin-on-a-chip for modeling ultraviolet-induced injury and evaluating photoprotective and regenerative modalities

Abstract

Ultraviolet B (UVB) irradiation is a major cause of acute skin damage and photoaging; however, human-relevant in vitro platforms for systematic evaluation of photoprotective and regenerative strategies are limited. Increasing demands for reproducibility and throughput in preclinical studies highlight the need for microphysiological skin models compatible with laboratory automation. We present a human skin-on-a-chip platform interfaced with an automated workstation (ProMEPS®) for modeling UVB-induced skin damage. The platform consists of human keratinocytes and dermal fibroblasts cultured on opposite sides of a microporous membrane in an 8-unit format chip. Following UVB exposure, the model exhibited increased oxidative stress, inflammatory activation, and extracellular matrix (ECM) remodeling, while showing reduced proliferation and barrier marker expression in both epidermal and dermal compartments, recapitulating key features of acute UVB injury and early photoaging. We evaluated the photoprotective effects of conventional UV protectants and the regenerative effects of stem cell-derived nanovesicles in UVB-injured skin. Laboratory automation enabled reproducible skin barrier formation and transepithelial electrical resistance (TEER) measurements, with consistently higher baseline TEER values than in manually prepared chips. These results establish the platform as a quantitative and scalable system for evaluating UVB-induced skin injury and advanced intervention strategies. By enabling standardized, automation-assisted modeling of UVB-induced skin injury with geometry-controlled and compartment-resolved readouts, this platform overcomes reproducibility and throughput limitations that constrain existing skin-on-a-chip models.