Topical Administration of Vitamin D2 Combined with Colloidal Silver Nanoparticles Promotes Wound Repair and Protection Against Skin Irritation and UVB Irradiation in 3D Reconstructed Human Skin Models

<b>Background/Objectives</b>: There is a great demand for novel, multipurpose, natural skin-care products in the global skin repair and sun protection markets. Within this framework, the potential benefits of topical Vitamin D2 (VD2) administration in combination with silver nanoparticles (AgNPs) were examined. <b>Methods</b>: Evaluating the efficacy of the VD2+AgNP cream in wound healing, skin irritation and UVB irradiation protection necessitated preclinical testing using reconstructed human skin equivalent models (prepared from human foreskins) containing both a fully stratified epidermal layer and underlying dermis. <b>Results</b>: Application of the cream significantly improved wound healing by stimulating keratinocyte re-epithelialization and dermal fibroblast migration in models subjected to full-thickness (scratch and biopsy punch) wounds, compared to untreated models. The VD2+AgNP cream, administered prior to the induction of skin irritation by 5% sodium dodecyl sulfate (SDS) afforded protection by ameliorating cell viability epidermal thickness and interleukin-1alpha levels. UVB exposure (50 mJ/cm²) significantly reduced cell viability and epidermal thickness (associated with increased epidermal breakage), as well as basal layer Ki67 and supra-basal layer involucrin expression, compared to the CTRL sham-irradiated models. The cream administered prior to UVB irradiation (protective capacity) showed greater efficacy in minimizing epidermal damage. This was reflected by significantly higher Ki67 and involucrin expression, as well as lower epidermal breakage, compared to models where the cream was applied following UVB irradiation (curative capacity). <b>Conclusions</b>: The VD2+AgNP cream shows multipurpose potential in skin protection. The underlying molecular mechanisms remain to be investigated.