Bifunctional sodium hyaluronate microneedle patches integrating 5α-reductase and ROS regulation for boosted hair regeneration.

Androgenetic alopecia (AGA) - induced progressive hair loss is a worldwide phenomenon primarily attributed to excessive dihydrotestosterone (DHT) and reactive oxygen species (ROS) within hair follicles. This leads to follicle atrophy and eventual loss, posing a significant challenge for hair regeneration in affected individuals. Herein, we designed a bifunctional sodium hyaluronate microneedle patch as an in situ medical intervention, incorporating glycyrrhizin-loaded dutasteride (GL-DUT) micelles as the 5α-reductase inhibitor to reduce DHT levels and mesoporous polydopamine nanoparticles (MPDA NPs) as the ROS scavenger. Dermal papilla cells (DPCs) were used as a representative model to evaluate the dual regulatory effects of GL-DUT micelles and MPDA NPs. The GL-DUT micelles effectively inhibited type 2 5α-reductase activity within hair follicle cells. At the same time, MPDA NPs efficiently reduced excessive ROS, thereby mitigating the conversion of testosterone to DHT and preventing hair follicle miniaturization. Furthermore, the bifunctional microneedle patch (D/M-MNs) demonstrated successful DHT inhibition and ROS elimination in vitro and in vivo, enhancing DPCs activity and significantly accelerating hair growth with good biocompatibility. These findings introduce a novel strategy for promoting rapid hair regeneration by inhibiting DHT in situ and eliminating ROS, offering a promising translational treatment for hair regeneration.