Abstract

Objectives: The study aimed to develop a novel PLA filler (PLA-IC) incorporating microlattice-encapsulated vitamin C and glutathione, and to evaluate its performance compared with conventional PLA. Specifically, it assessed antioxidant stability, collagen induction, and tissue response (including inflammation and neovascularization). The goal was to determine whether modulation of oxidative stress and the local microenvironment could improve the predictability and biological performance of PLA fillers. Introduction: PLA fillers are widely used for their collagen-stimulating effects but are associated with early inflammation, oxidative stress, and variability in tissue remodeling. Degradation of PLA lowers local pH and promotes oxidative stress, impairing fibroblast function and collagen synthesis. Vitamin C and glutathione support collagen formation and redox balance but are unstable in conventional systems. Microlattice encapsulation is proposed as a strategy to stabilize these antioxidants, enabling controlled release and improving the biological environment around PLA particles. Materials / method: PLA-IC was prepared by combining PLA microspheres with microlattice-encapsulated vitamin C and glutathione. Particle morphology was analyzed using SEM and TEM. Antioxidant stability was evaluated via HPLC and DPPH assays over long-term storage (up to 277 days). In vivo, SKH mice received subcutaneous injections of PBS, conventional PLA, or PLA-IC. Volume changes were measured using Primos imaging, and histological analyses (H&E and Masson’s trichrome staining) were performed to assess inflammation, neovascularization, and collagen deposition over 12 weeks. Results: Microlattice encapsulation preserved vitamin C and glutathione stability for up to 277 days and maintained antioxidant activity for 200 days. In vivo, PLA-IC demonstrated significantly greater volume increase than conventional PLA from weeks 4 to 12. Collagen deposition was nearly twofold higher at 12 weeks. Histological analysis showed reduced inflammatory cell infiltration and lower neovascularization in the PLA-IC group, indicating a more controlled and favorable tissue response. Conclusion: PLA-IC exhibited enhanced antioxidant stability, increased collagen formation, improved volume retention, and reduced inflammatory and vascular responses compared with conventional PLA. These findings suggest that microlattice-based antioxidant incorporation can improve both the efficacy and consistency of biostimulatory fillers. PLA-IC shows potential advantages for aesthetic soft-tissue augmentation, although further long-term and clinical studies are required to confirm safety and efficacy.