Enhancement of osteoinduction by continual simvastatin release from poly(lactic-co-glycolic...

Simvastatin is considered as a stimulator for bone formation. However, the half-life for simvastatin is generally 2 hours, which means, it is difficult to maintain biologically active simvastatin in vivo. To overcome this limitation, we created a system to slowly release simvastatin in vitro and in vivo. We constructed a poly(lactic-co-glycolic acid)/hydroxyapatite nano-fibrous scaffold to carry simvastatin. Releasing assays showed that simvastatin was released from poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin quickly within - 15 days, and small amounts continued to be released through day 56 (experiments terminated). MTT assays demonstrated that both poly(lactic-co-glycolic acid)/hydroxyapatite and poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin promoted MC3T3-E1 cell proliferation. However, Alkaline phosphatase assays showed that only poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold significantly promoted the osteogenic differentiation of MC3T3-E1 cells in vitro on day 14. To further test in vivo, we created calvaria bone defect models and implanted either poly(lactic-co-glycolic acid)/hydroxyapatite or poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin. After 4 or 8 weeks post-implantation, the results indicated that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold induced bone formation more efficiently than poly(lactic-co-glycolic acid)/hydroxyapatite alone. Our data demonstrates that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin has the potential to aid in healing bone defects and promoting bone regeneration in the future although we still need to optimize this complex to efficiently promote bone regeneration.