Curcumin-primed milk-derived extracellular vesicles remodel hair follicle microenvironment for the treatment of androgenetic alopecia.

Androgenetic alopecia (AGA) is a globally prevalent condition, with limited treatment options and significant adverse effects associated with existing therapies. The primary pathogenic mechanisms of AGA involve androgen-mediated regulatory pathways, molecular alterations affecting hair regeneration, and inflammation in the perifollicular microenvironment. In this study, we first investigated the topical application of testosterone with varied doses for AGA mouse model induction, in which the High-dose group exhibited the most robust model development and provided a more comprehensive set of criteria for successful AGA model establishment. Then, curcumin-primed milk-derived extracellular vesicles (Cur-mEVs) were fabricated for the therapy of AGA with the in-house developed mouse model described above. It was demonstrated that Cur-mEVs remodeled the hair follicle microenvironment, evidenced by the activation of the Wnt/β-catenin signaling pathway, downregulation of transforming growth factor beta 1 expression and alleviation of perifollicular inflammation. These effects collectively regulated the hair follicle cycle and promoted hair regeneration. Overall, our results highlighted a promising therapeutic approach for AGA with potential translational possibilities.