Long-Term Biostimulatory Efficacy of Polycaprolactone Facial Fillers: A Two-Year Quantitative Assessment of Neocollagenesis Using Second-Harmonic Generation Microscopy

BACKGROUND: Polycaprolactone (PCL) microsphere-based facial fillers are used for aesthetic enhancements but understanding their long-term biostimulatory efficacy in inducing neocollagenesis requires precise, quantitative structural evaluation. OBJECTIVES: To investigate and quantitatively assess the long-term efficacy of PCL facial fillers (e.g., Ellansé-S) in driving collagen regeneration and structural remodeling. METHODS: Using a two-year subcutaneous rabbit model (n=30), the study integrated advanced second harmonic generation (SHG) microscopy for high-resolution imaging. Automated image analysis software (CT-FIRE V3.0 and CurveAlign V5.0) was used to quantify collagen density, alignment, and structural parameters. RESULTS: Sustained neocollagenesis was demonstrated throughout the 24-month period, marked by significant increases in collagen fiber density and network maturation (improved fiber alignment). Compared with tissue without implanted material, the density of the collagen fiber network increased by 79.2% at 12 months, after which it began to decline. This result was consistent with clinical observations. Crucially, the structure and organization of the regenerated collagen did not differ significantly from native tissue. CONCLUSIONS: PCL fillers provide immediate volumization along with durable, physiologically integrated tissue regeneration, proving sustained neocollagenesis over a two-year period.