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.
Highlights
There was an urgent need of engineered-organ transplantation for treating bone-related diseases, such as the bone tumor, osteoporosis, and osteonecrosis of the femoral head (ONFH)
Several reports proved that many soluble growth factors could regulate vasculogenesis and angiogenesis, mainly including the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), platelet-derived growth factor-BB (PDGF-BB), monocyte chemoattractant protein-1 (MCP-1), etc. [7,8,9,10,11]
The simultaneous delivery system for releasing VEGF and MCP-1 could be facilely constructed by using a linear PLGA-mPEG block copolymer microspheres carrier
Summary
There was an urgent need of engineered-organ transplantation for treating bone-related diseases, such as the bone tumor, osteoporosis, and osteonecrosis of the femoral head (ONFH). Sci. 2018, 8, 2438 including angiogenesis and osteogenesis [1,2,3,4]. Thereinto, the ingrowth of new blood vessels was critical for stimulating osteogenesis, and the formed capillary network served as a template for new bone formation [5]. Several reports proved that many soluble growth factors could regulate vasculogenesis and angiogenesis, mainly including the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), platelet-derived growth factor-BB (PDGF-BB), monocyte chemoattractant protein-1 (MCP-1), etc. VEGF was one of the most important growth factors across all stages of neovascularization, mainly through initiating the sprouting of existing blood vessels by mitogenic and chemotactic effects, and facilitating the recruitment of circulating endothelial progenitor cells [9,10]. VEGF was important for maintaining the survival of blood vessels, the data indicated that the withdrawal of VEGF caused vascular collapse and regression [9,10,11]
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