Silk-Coated Disc Plga Microparticles With Simvastatin Enhance Bone Regeneration

Current bone substitutes lack dual osteoconductive and osteoinductive properties, limiting guided bone regeneration (GBR) efficacy (Zhang et al., Colloids Surf B Biointerfaces, 2021, 199:111560). This study optimized disc-shaped PLGA microparticles (dPLGA) via silk fibroin (SF) coating and simvastatin (SIM) loading to address these limitations. SF-modified SIM-loaded dPLGA (SF-SIM@dPLGA) was synthesized using a double emulsion-solvent evaporation method. In vitro biocompatibility, osteogenic differentiation (ALP/ARS staining, qRT-PCR), and drug release kinetics were evaluated. In vivo cranial defect regeneration in 6-week-old male rats (approved by IRM-DWLL2021121) was assessed via micro-CT, histology (H&E/Masson), and coagulation assays. SF-SIM@dPLGA was synthesized via double emulsion-solvent evaporation and chemical cross-linking. In vitro studies demonstrated enhanced biocompatibility, promoted BMSC adhesion/migration (via scratch assay), and stimulated osteogenic differentiation (ALP/ARS staining, Runx2/Alp/Opn expression). In vivo rat cranial defect models revealed accelerated bone regeneration (micro-CT/histology) and improved hemostasis (plasma recalcification, tail amputation assay), with no adverse effects on major organs (H&E/blood tests). SF-SIM@dPLGA combines the osteoconductive disc-shaped PLGA structure, osteoinductive SIM release, and SF-enhanced biocompatibility/adhesiveness, synergistically promoting bone regeneration. This adhesive hemostatic bone filler demonstrates clinical potential for GBR.