Living Probiotic Microneedles Coordinate Antiandrogen and Nitric Oxide Therapy for Androgenetic Alopecia.

Androgenetic alopecia (AGA) is characterized by follicular miniaturization mediated by androgens along with chronic inflammatory and vascular disturbances. These alterations suggest broader dysregulation involving endocrine pathways, immune activity, and vascular function. Current therapies such as finasteride and minoxidil provide limited and often transient improvement because they target only single components of this multifactorial process. In this study, we developed a living probiotic-based microneedle system that integrates nitric oxide-generating Weissella cibaria (WC) with clascoterone (Cla)-loaded polymeric nanoparticles to enable coordinated modulation of androgen signaling and local tissue repair. The dissolvable microneedles deliver viable WC and Cla directly into the dermis, where WC-derived nitric oxide enhances endothelial activation and promotes an anti-inflammatory macrophage phenotype, while Cla protects dermal papilla cells from dihydrotestosterone-induced suppression. In vitro, the platform mitigated androgen-related cytotoxicity, supported endothelial migration, and reduced inflammatory cytokine secretion. In a testosterone-induced mouse model, treatment accelerated entry into anagen, improved hair density, enhanced vascular regeneration, and attenuated perifollicular inflammation. These findings indicate that the combined probiotic and drug delivery strategy achieves restoration of the hair follicle microenvironment together with androgen blockade and represents a promising minimally invasive approach for the treatment of AGA.