Microneedle based adipose derived stem cells‐derived extracellular vesicles therapy ameliorates UV‐induced photoaging in SKH‐1 mice

Abstract Extracellular vesicles from adipose derived stem cells (ADSCs‐EVs) have shown immunomodulation and anti‐photoaging effects; however, the skin barrier prevents their absorption via skin. Meanwhile, microneedle (MN) is a widely used and minimally invasive tool for dermal delivery of drugs, it also has neocollagenesis effect by creating tiny injuries and initiating wound healing process. To investigate the effect of MN combined with ADSCs‐EVs on skin aging, photoaging in SKH‐1 mice was induced by chronic exposure to ultraviolet radiation. Then the mice were treated following a split‐dorsal scheme, in which one side had MN alone or MN + EVs treatment and the other side was left untreated. For the side treated with MN alone or MN + EVs, the epidermal thickness was decreased and the skin barrier function was enhanced compared with the untreated side. However, MN + EVs group showed the least wrinkles, the highest collagen density and the most organized collagen fibers among the three groups. The level of CD11b + cell infiltration was lower in MN + EVs group than that in the MN group at 3 day after the treatment. These results indicated that MN treatment alone could improve epidermal structure and function of photoaging skin, and a combination with ADSCs‐EVs would accelerate the restoration of inflammation caused by MN and improve the content of collagen. In all, this study indicated that a combination of MN and topical applied ADSCs‐EVs was a feasible and safe strategy to ameliorate photoaging, providing a new avenue for safe administration of EVs.