Abstract
Androgenic alopecia (AGA), the most common form of progressive hair loss in both males and females, significantly impacts patients' quality of life and confidence. Current therapies, such as minoxidil, are limited by poor patient compliance and low transdermal bioavailability, highlighting the need for more effective treatments. In this study, we identified collagen XVII (COL17) as a key player in AGA-like model pathogenesis, observing its significant downregulation in a testosterone-induced AGA-like mouse model. This reduction was accompanied by abnormal hair follicle morphology, decreased proliferation and impaired angiogenesis. To address this, we developed recombinant human COL17 fragment (800-1300 aa) (rhCOL17p) expressed and purified from E. coli, which demonstrated dose-dependent enhancement of dermal papilla cell adhesion, migration and proliferation in vitro. To overcome transdermal delivery challenges, we designed a dissolving microneedle (MN) patch using hyaluronic acid as a matrix. The rhCOL17p-MN achieved 96% skin penetration and sustained release of 96% within 28 h in vitro, with residual fluorescence detectable in mouse skin for up to 6 days. In vivo, the 4-mg/ml rhCOL17p-MN achieved a mean hair coverage of ∼97% by Day 14, which was statistically equivalent to the efficacy of 5% minoxidil, with increased follicle density, anagen-phase transition and CD31+ vascularization. Histological analysis revealed restored follicle structure and upregulated β-catenin+ and SRY-box gene 9 (SOX9+), indicating activation of stem cell and proliferative signaling pathways. The rhCOL17p-MN also demonstrated low hemolysis (<0.5%) and robust mechanical stability (≥0.2 N/needle), confirming its safety and feasibility. These findings establish COL17 downregulation as a critical mechanism in AGA and demonstrate that MN-delivered rhCOL17p promotes hair regeneration through multi-pathway regulation, offers preclinical evidence supporting its potential as a candidate strategy for further investigation in AGA-related research.