Composite Hydrogels with the Simultaneous Release of VEGF and MCP-1 for Enhancing Angiogenesis for Bone Tissue Engineering Applications

Abstract

Rapid new microvascular network induction was critical for bone regeneration, which required the spatiotemporal delivery of growth factors and transplantation of endothelial cells. In this study, the linear poly(d,l-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (PLGA-mPEG) block copolymer microspheres were prepared for simultaneously delivering vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1). Then, vascular endothelial cells (VECs) with growth factor loaded microspheres were composited into a star-shaped PLGA-mPEG block copolymer solution. After this, composite hydrogel (microspheres ratio: 5 wt%) was formed by increasing the temperature to 37 °C. The release profiles of VEGF and MCP-1 from composite hydrogels in 30 days were investigated to confirm the different simultaneous delivery systems. The VECs exhibited a good proliferation in the composite hydrogels, which proved that the composite hydrogels had a good cytocompatibility. Furthermore, in vivo animal experiments showed that the vessel density and the mean vessel diameters increased over weeks after the composite hydrogels were implanted into the necrosis site of the rabbit femoral head. The above results suggested that the VECs-laden hydrogel composited with the dual-growth factor simultaneous release system has the potential to enhance angiogenesis in bone tissue engineering.