Microneedle‐Assisted Delivery of PEGylated Recombinant Human Fusion Collagen for Androgenetic Alopecia: Preclinical and Pilot Clinical Evidence

Background Androgenetic alopecia (AGA), the most common form of progressive hair loss in men, significantly impairs both physical and psychological well‐being. While traditional research has predominantly focused on cellular components and signaling pathways, the extracellular matrix (ECM)—particularly collagen—is increasingly recognized as playing a dual role: serving as both a structural scaffold and a dynamic signaling reservoir for hair follicles. Consequently, a recombinant fusion collagen that integrates key functional domains of human types III and XVII collagen with hair follicle‐targeting sequences represents a promising strategy for ECM replenishment and functional restoration. Aims This study aimed to evaluate the therapeutic feasibility and underlying mechanisms of microneedle‐assisted delivery of PEGylated recombinant human fusion collagen (PEG‐rhCol‐F) for AGA treatment. Methods The therapeutic efficacy of microneedle‐delivered PEG‐rhCol‐F was first evaluated in a testosterone‐induced AGA mouse model through morphological, histological, and molecular analyzes (Western blotting). Subsequently, a three‐month pilot clinical trial involving 15 AGA patients was conducted. Patients received microneedling combined with a PEG‐rhCol‐F liquid dressing, and treatment outcomes were assessed via trichoscopy. Results In the AGA mouse model, PEG‐rhCol‐F treatment significantly promoted hair regrowth, increased hair follicle count, and facilitated the transition to the anagen phase. Mechanistically, this was associated with the activation of the Wnt/β‐catenin‐VEGF axis. Correspondingly, the clinical trial demonstrated a marked improvement in hair density and diameter from baseline, along with a shift from vellus to terminal hairs. The treatment regimen was well‐tolerated, with only mild, transient adverse reactions (e.g., erythema) observed. Conclusions This pilot study provides initial evidence for the efficacy and safety of microneedle‐assisted PEG‐rhCol‐F delivery for AGA patients. By combining structural ECM repair with functional pathway activation, this dual‐mechanism approach merits further clinical investigation.