Controlled release of simvastatin using a biodegradable polymer for bone healing application

Extensive bone defects arising from trauma, disease, congenital abnormalities, or impaired fracture healing remain a major challenge in orthopaedics, as their size often surpasses the intrinsic regenerative capacity of bone, necessitating grafts, biomaterial scaffolds, or advanced regenerative approaches for effective structural and functional restoration. In this study, a simvastatin-loaded poly(lactic acid) (PLA)-based polymer matrix has been developed for localized and sustained drug delivery. Unlike previously reported simvastatin-loaded PLA formulations, this study presents a porous biodegradable PLA scaffold whose physicochemical characteristics, crystallization behaviour, thermo-mechanical and rheological properties are systematically correlated with sustained simvastatin release, osteoblast proliferation, and long-term regeneration of critical-sized bone defects in a rabbit model, demonstrating its potential as a multifunctional implantable bone graft substitute. The system provides temporary structural support, controlled simvastatin release (85.7% after 72 h), and enhanced osteogenic activity through MG63 cell proliferation for effective repair of critical bone defects. In vitro investigations further revealed that the system maintains remarkable cytocompatibility toward normal 3T3-L1 fibroblast cells (∼99 ± 3% viability at 20 µg mL^-1@72 h), while significantly enhancing MG63 osteoblastic cell proliferation (∼95 ± 6% viability). In vivo evaluation demonstrated that the implanted scaffold exhibited progressive biodegradation, extensive osteoid deposition, cellular infiltration, and complete replacement of the scaffold by newly regenerated bone tissue within 20 weeks. It is found that the scaffold achieved complete cortical bridging of the critical-sized ulnar defect. The experimental groups showed no evidence of severe inflammation, thereby providing objective evidence for the scaffold's in vivo performance.