Local Delivery of BMP-2 from Poly(lactic-co-glycolic acid) Microspheres Incorporated into Porous Nanofibrous Scaffold for Bone Tissue Regeneration

摘要

The integration of porous scaffold and growth factor is widely accepted as an emerging and powerful strategy for bone tissue regeneration. Herein, we fabricated the polymeric scaffold with macroporous and nanofibrous architecture that composed of poly(L-lactic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) using thermally induced phase separation (TIPS) technique. The bone morphogenetic protein-2 (BMP-2) loaded PLGA microspheres (MS) were prepared and then incorporated into nanofibrous scaffold (NF scaffold) to obtain the BMP-2-loaded composite scaffold (BMP-2@ MS/NF scaffold). The in vitro release behavior of BMP-2 from the composite scaffold showed a sustained release of over 5 weeks. The mouse primary osteoblasts (mOBs) grown on these BMP-2-loaded composite scaffolds showed better adhesion and proliferation than those grown on the scaffolds without BMP-2 loading. Also, the BMP-2-loaded composite scaffolds displayed enhanced in vitro osteogenic differentiation of osteoblasts, as evidenced by the results of alkaline phosphatase (ALP) activity and Alizarin Red S staining. In addition, histology from an in vivo osteogenic potential evaluation from a rat calvarial defect model demonstrated high osteoinductivity of these BMP-2-loaded composite scaffolds. These results suggested that constructed BMP-2-loaded composite scaffold had the potential to be used as a bone implant, whose osteogenic ability was promoted by the prolonged release of BMP-2.