Development of a controlled ex vivo human skin platform for quantitative evaluation of age-related functional biomarkers following application of topical treatments.

Targeting cellular senescence presents a promising approach to slow visible skin aging and promote tissue repair. However, most preclinical models fail to capture the full architecture of human skin or accommodate diverse skin types, limiting their translational relevance. To address this gap, we developed a controlled ex vivo human skin explant platform using freshly acquired tissues from donors of varying ages and Fitzpatrick skin types. This model applies standardized UVA and UVB doses to induce reproducible photodamage, enabling the assessment of both preventative and reparative effects of topical treatments. The results showed that ND-ZnO and NAC reduced levels of p16^INK4a and p53, which are key biomarkers measuring cellular senescence; ND-ZnO and exosomes lowered IL-1β expression, which is a biomarker measuring inflammation. Histological analysis confirmed these findings, with ND-ZnO-treated skins preserved epidermal structure, reduced inflammatory features, and maintained dermal collagen organization. We then conducted a four-week single-patient case study using the same ND-ZnO formulation. Visible improvements in redness, pigmentation, and texture were observed, aligned with the molecular and histological changes seen ex vivo. These findings suggested that the ex vivo platform has the potential to be used as a more inclusive, human-relavent model for evaluating and quantifying the anti-aging efficacies of topical treatments across diverse skin types and age groups.