Repair of rat calvarial bone defects by controlled release of rhBMP-2 from an injectable bone regeneration composite

Abstract

The objective of the present study was to enhance the regeneration ability of an injectable bone regeneration composite (IBRC) by the controlled release of recombinant human bone morphogenetic protein-2 (rhBMP-2). The IBRC comprised nano-hydroxyapatite/collagen (nHAC) particles in an alginate hydrogel carrier. First, bovine serum albumin (BSA) as a model protein was released from IBRC to evaluate its release rules. The results suggested that IBRC is a good controlled release carrier for BSA in the range 5-75 µg/ml. In the in vitro study the rhBMP-2 released from IBRC was determined by an enzyme-linked immunosorbent assay specific for rhBMP-2. The bioactivity of the released rhBMP-2 was evaluated through differentiated function of marrow mesenchymal stem cells (MSCs), as measured by alkaline phosphatase activity. The results of an in vitro study confirmed that rhBMP-2 released continuously for 21 days, and its bioactivity was well preserved during this period. The bone formation ability was assessed using a rat calvarial defect model of critical size. Micro-computed tomography (micro-CT) and histological analysis demonstrated that the IBRC had good bone formation ability, which was promoted through rhBMP-2 released from IBRC/rhBMP-2. In vitro and in vivo studies suggested that the present system is a potential bone critical defect repair material for clinical applications.