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.