Chitin Derivative-Based Detachable Microneedles for Effective Treatment of Androgenic Alopecia.

Androgenic alopecia (AGA) is the most common type of hair loss in clinical practice, which not only compromises scalp physiology but also induces psychological comorbidities. Despite its high prevalence, current therapeutic interventions for AGA remain constrained by prolonged treatment durations, notable safety risks, and prohibitive expenses. To address these limitations, we engineered detachable microneedles incorporating TEMPO-oxidized chitin derivatives (CD MNs), which demonstrated unprecedented hair regenerative capacity. In C57BL/6j AGA models, CD MNs induced 71.56% ± 14.20% hair regrowth density at day 16 (vs. 32.23% ± 14.55% for 5% minoxidil, the current clinical gold standard). Ex vivo AGA hair follicle exhibited 0.93 ± 0.15 mm hair shaft elongation under chitin derivatives treatment within 5 days, which is comparable to minoxidil. Mechanistic profiling via single-cell RNA sequencing identified CD MNs mediated suppression of lysosomal hydrolases and membrane proteins, indicating autophagy potentiation. Further ex vivo studies confirmed that chitin derivatives promoted hair growth by activating the hair follicle autophagy. Notably, the microneedle system exhibited no detectable dermal or visceral toxicity. To our knowledge, this study is the first to report the anti-AGA activity of chitin derivatives. Our findings established a robust theoretical foundation and preclinical validation for chitin-based biomaterials as next-generation AGA therapies, offering a safe, cost-effective alternative to conventional therapies.