Sequential delivery of BMP-7 and IGF-I to enhance the osteoinductive property of deproteinized bovine bone

Abstract

As an alternative to autogenous bone grafting, deproteinized bovine bone (DBB) is a widely used scaffold for bone repair. However, it lacks intrinsic osteoinductivity. The aim of this study was to improve the osteoinductivity of DBB for clinical bone repair through sequential delivering bone morphogenetic protein-7 (BMP-7) and insulin-like growth factor-I (IGF-I). By culturing adipose-derived mesenchymal stem cells (ASCs) with different concentrations of BMP-7 and IGF-I, the optimal dose was determined to enhance cell proliferation and osteogenic differentiation. Osteogenic related genes (Runx2, OPN and ALP) were investigated to evaluate the effects of sequential application of growth factors on osteogenic differentiation of ASCs. Then the optimal delivery system with sequential release of BMP-7 and IGF-I was developed on DBB by IGF-I incorporated calcium phosphate (CaP) coating and BMP-7 adsorption (IGF-I inc. & BMP-7 ads.). ASCs were cultivated on the scaffolds to investigate cell adhesion and osteogenic differentiation in vitro. IGF-I inc. & BMP-7 ads. DBB increased the alkaline phosphatase (ALP) activity of ASCs. In vivo, ectopic bone formation was examined using rat models. Osteoid tissue was observed to be greatest in the IGF-I inc. & BMP-7 ads. group compared with the other groups six weeks after implantation. In vitro and in vivo results of this study suggested that sequential release of BMP-7 and IGF-I could enhance the osteoinductive property of DBB.