Ni–Cu Bimetallic Nanozyme and Minoxidil Co-Loaded Dissolving Microneedles Reshape Hair Follicle Microenvironment for Androgenic Alopecia Treatment

Androgenetic alopecia (AGA) is a prevalent dermatological disorder. Conventional minoxidil (MXD)-based therapies suffer from limitations such as low bioavailability and frequent dosing, necessitating the development of safer and more effective treatment strategies. Herein, we developed a dissolvable microneedle system (NC&MXD MNs) coloaded with nickel–copper nanozymes (NC) and MXD, which remodels the hair follicle microenvironment through synergistic dual-functional reactive oxygen species (ROS) scavenging and mechanostimulation-enhanced angiogenesis. The NC nanozymes demonstrated remarkable SOD-like and CAT-like activities, efficiently decomposing H₂O₂ into O₂, while the microneedles achieved rapid drug release with a transdermal efficiency of 83.4% (penetration depth: 200–300 μm). Moreover, the mechanical stimulation from microneedles promoted angiogenesis and improved local blood flow. In AGA mouse models, NC&MXD MNs enhanced hair regeneration coverage to 93.7% (vs 85.1% for MXD alone), increased Ki67+ cell proliferation by 1.9-fold, and significantly thickened regenerated hair diameter. Additionally, this system reduced ROS levels by 2.3-fold and increased CD31+ vascular density by 40%, markedly improving the microenvironment. The proposed nanozyme-microneedle combinatorial strategy offers a safe, minimally invasive, and highly effective therapeutic approach for AGA.