Poly(γ-glutamic acid)-thickened PLLA microspheres with enhanced biocompatibility and efficacy in aged mice

Poly(L-lactic acid) (PLLA) microspheres are widely used in aesthetic and regenerative medicine to promote collagen remodeling, but their efficacy and long-term safety lack sufficient experimental data. In this study, a poly(γ-glutamic acid)-thickened PLLA microsphere formulation (PLLA-γ-PGA) was developed, and its biocompatibility and efficacy were evaluated in an aged mice model induced by subcutaneous injection of D-galactose combined with UV irradiation. As a result, PLLA-γ-PGA significantly enhanced dermal fibroblast activation, promoted sustained tissue remodeling and elicited milder inflammatory responses without observable adverse effects, outperforming marketed hyaluronic acid (HA) fillers and PLLA-carboxymethyl cellulose sodium (PLLA-CMC) formulations. These findings present PLLA-γ-PGA as a safe and efficacious regenerative material, providing robust preclinical evidence to support its translational potential for long-term skin rejuvenation.