Injectable PEG-PCL-PEG Copolymers for Skin Rejuvenation: In Vitro Cell Studies to in Vivo Collagen Induction

In this study, we designed an injectable skin-rejuvenating formulation based on polyethylene glycol-polycaprolactone-polyethylene glycol (PEG-PCL-PEG) copolymers to provide a synergistic combination of biocompatibility, antioxidative capacity, and regenerative potential. Through the systematic optimization of the precursor molar ratio and molecular weight, well-defined PEG-PCL-PEG copolymers were synthesized and structurally characterized using gel permeation chromatography (GPC), proton nuclear magnetic resonance (¹H-NMR), and Fourier transform infrared (FT-IR) spectroscopy. An optimized precipitation and drying protocol effectively reduced residual solvents, as confirmed by gas chromatography (GC). Idebenone was incorporated as an antioxidant to prevent skin aging, while hyaluronic acid (HA), L-arginine, and glycerin were included to promote collagen regeneration. In vitro assays demonstrated that idebenone-loaded samples exhibited prolonged intracellular antioxidant activity with low cytotoxicity. The collagen-promoting formulation, containing HA, glycerin, and L-arginine, enhanced the expression of transforming growth factor-β (TGF-β) and type III collagen (COL3) while suppressing inflammatory genes, suggesting a favorable environment for extracellular matrix remodeling. In vivo evaluation corroborated these outcomes, showing angiogenesis, collagen reorganization, and progressive dermal thickness. Histological analysis further confirmed sustained matrix regeneration and tissue integration. These results highlight the potential of PEG-PCL-PEG-based injectables as a multifunctional platform for collagen regeneration, offering a promising strategy for both cosmetic and clinical applications.