Fibrin Glue/Fibronectin/Heparin-Based Delivery System of BMP2 Induces Osteogenesis in MC3T3-E1 Cells and Bone Formation in Rat Calvarial Critical-Sized Defects

Abstract

Bone morphogenetic proteins (BMPs) have been used to promote bone formation in many clinical scenarios. However, the BMPs are inherently unstable in vivo and therefore need to be combined with carriers for controlled delivery. In this study, an innovative and efficient fibrin glue/fibronectin/heparin (FG/Fn/Hep)-based delivery system was developed for controlled release of BMP2. The incorporation of heparin can significantly slow the release of BMP2 without substantially affecting the structure and stiffness of the FG/Fn. The BMP2 release from the FG/Fn/Hep-BMP2 hydrogel is largely dominated by hydrogel degradation rather than simple diffusion. In vitro release experiments and MC3T3-E1 cell induction experiments showed that BMP2 can be released steadily and can induce MC3T3-E1 cells to differentiate into osteoblasts efficiently. This process is characterized by the significantly increased expression of calcium deposits, alkaline phosphatase, runt-related transcription factor-2, osteopontin, osteocalcin, and collagen I in comparison with the negative control. In vivo assessments revealed that the FG/Fn/Hep-BMP2 hydrogel significantly promotes bone regeneration in a rat calvarial critical-sized defect model. Our investigation indicates that FG/Fn/Hep-BMP2 hydrogel holds promise to be used as an alternative biomaterial for the repair of bone defects.

Keywords: biomineralization; bone morphogenetic proteins; fibrin glue; fibronectin; heparin.