Abstract

Objectives: To evaluate the biostimulatory mechanisms and clinical efficacy of Poly-D,L-Lactic Acid (PDLLA) in treating hair loss driven by hair follicle stem cell (HFSC) dysfunction and dermal papilla cell (DPC) senescence. Introduction: Age-related alopecia is linked to follicular and sebaceous decline caused by cumulative oxidative stress. PDLLA is a biocompatible polymer that induces angiogenesis and tissue regeneration. Its combination with microneedling enhances scalp delivery and maximizes regenerative potential. Results: Preclinically, PDLLA activates Piezo1-mediated mechanotransduction in macrophages, promoting M2 polarization and HGF/IGF-1 secretion. This triggers Wnt/β-catenin signaling to induce HFSC proliferation and prolong the anagen phase. Additionally, PDLLA acts as a "senomorphic," reducing DPC oxidative stress (8-OHdG) and upregulating structural keratins (K35, K85), thereby restoring hair thickness and shine. Clinically, 90% of patients showed Global Aesthetic Improvement Scale (GAIS) improvement at week 12 with no serious adverse events. Conclusion: PDLLA-HA reverses age-associated follicular decline by remodeling the microenvironment and suppressing senescence-associated phenotypes. It represents a promising, well-tolerated regenerative therapy for non-scarring alopecia.