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Ultraviolet (UV) radiation from the sun or artificial sources is one of the primary causes of skin damage, including sunburns, tanning, erythema, and skin cancer. Among the three different types of UV rays, UVB rays have a medium wavelength that can penetrate the epidermal layer of the skin, resulting in sunburn, suntan, blistering, and melanoma in case of chronic exposure. This study aimed to evaluate the preventive and therapeutic effects of a gel-in-oil nanogel dispersion (G/O-NGD) as a transdermal delivery biomolecular carrier for skin damage caused by UVB light. The efficacy of this carrier against UVB-induced skin damage was investigated in vivo by delivering different growth factors (GFs) encapsulated in a G/O-NGD. Artificial UVB light was used to induce skin damage in nude mice, followed by the transdermal application of five GF [vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor (TGF)-1, and insulin-like growth factor (IGF)-α]-immobilized G/O-NGD. Among these GFs, VEGF and bFGF promoted angiogenesis, while EGF, TGF-1, and IGF-α promoted the repair and regeneration of damaged cells. The results showed that G/O-NGD was superior to heparin-immobilized G/O-NGD in reducing UVB-induced skin damage, such as erythema, epidermal water reduction, inflammation, and dermis thickening. In addition, G/O-NGD could prevent and treat abnormal follicle proliferation caused by UVB rays and exhibited potential to repair lipid glands. Overall, our results demonstrate the potential of G/O-NGDs for the treatment of UVB-induced skin damage., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)