Porous Chitosan/Nano-Hydroxyapatite Composite Scaffolds Incorporating Simvastatin-Loaded PLGA Microspheres for Bone Repair

Abstract

The combination of bone tissue scaffolds with osteogenic induction factors is an effective strategy to facilitate bone healing processes. Here, chitosan (CS)/nano-hydroxyapatite (HA) scaffolds containing simvastatin (SIM)-loaded PLGA microspheres were fabricated by combining a freeze-drying technique with a modified water-oil-water emulsion method. The CS/HA weight ratio of 1:2 was selected by analyzing the effect of HA content on the micro-architecture, mechanical strength, and biocompatibility of the scaffold. Drug release kinetics showed that the SIM encapsulated in the scaffold was released in a sustained manner for up to 30 days. In vitro bioactivity study in rat bone marrow-derived mesenchymal stem cells showed that the SIM-loaded scaffolds had a strong ability in accelerating cell proliferation and inducing osteogenic differentiation. Moreover, an in vivo experiment using a rat calvarial defect model also documented that the SIM-loaded scaffolds had a remarkable effect on bone-promoting regeneration. The results of this study suggest that the SIM-loaded CS/HA scaffold is feasible and effective in bone repair and thus may provide a promising route for the treatment of critical-sized bone defects.