Enhanced osteogenesis and therapy of osteoporosis using simvastatin loaded hybrid system

Abstract

Postmenopausal osteoporosis is a common chronic dynamic bone disorder, caused by estrogen deficiency. To address this issue, we constructed a controlled drug-release system composed of poly (N-isopropylacrylamide) brush modified mesoporous hydroxyapatite (MHA-SIM-P) loaded with simvastatin (SIM) using an ovariectomised (OVX) rat model. Quantitative alkaline phosphatase activity assay, alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability in vitro. The results showed that the MHA-SIM-P nanoparticles significantly improved the osteogenic differentiation of OVX bone marrow stromal cells (BMSCs) in vitro. In osteoporotic animal model, the therapeutic efficiency for bone defect was evaluated by μCT analysis, tartrate-resistant acid phosphatase, haematoxylin and eosin staining, which showed improved bone formation and less osteoclastic response in OVX rats after surgery for 3 and 6 weeks. This polymer brush modified MHA system provided a sustained release system of hydrophobic SIM to inhibit osteoporosis together with MHA nanoparticle promoting the osteogenesis. Thus, this novel strategy exhibited great potential for promoting osteogenic ability and treating local osteoporotic defects.

Keywords

• Osteogenesis
• Osteoporosis
• Mesoporous hydroxyapatite
• Bone marrow stromal cells
• Drug release