Microvascular remodeling strategy for skin rejuvenation through microenvironmental reprogramming and appendage restoration.

Skin photoaging, induced by excessive ultraviolet exposure, leads to microvascular and appendage degeneration, extracellular matrix degradation, and cellular senescence. The limited efficacy of current treatments for photoaging is partly due to underlying microvascular dysfunction. This study introduces a microneedle patch incorporating decellularized adipose-derived matrix (DAM) to enhance microvascular remodeling and mitigate photoaging. In vitro studies demonstrate that DAM enhances the function of photoaged endothelial cells via the VEGFA/PI3K/Akt pathway while simultaneously alleviating senescence in both fibroblasts and keratinocytes through intercellular communication. In a UVB-induced photoaged mouse model, DAM promotes angiogenesis, reduces matrix metalloproteinase expression, and stimulates collagen synthesis, ultimately restoring local homeostasis and reversing aging signs. Notably, DAM treatment not only reverses these signs but also regulates the hair follicle cycle, underscoring its dual impact on appendage regeneration and microvascular repair. In conclusion, the integration of DAM into a microneedle patch provides a clinically translatable and minimally invasive platform for addressing photoaging. These findings not only advance the understanding of photoaging mechanisms but also propose a novel microvascular-focused strategy for skin regeneration. Future research will focus on optimizing patch design and establishing standardized DAM quality control protocols, with potential applications in other age-related disorders.