Injectable temperature-sensitive hydrogel with VEGF loaded microspheres for vascularization and bone regeneration of femoral head necrosis

Abstract

The formation of neovascularization inside the bone scaffold could enhance and accelerate the regeneration of large bone defects in femoral head necrosis, the angiogenic growth factors are predominantly expressed during the early phase for a reestablishment of the vascularity. In this paper, the injectable temperature-sensitive star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (PLGA-mPEG) block copolymer was developed, during the sol-gel transition process, the vascular endothelial growth factor (VEGF) loaded linear PLGA-mPEG block copolymer microspheres and vascular endothelial cells (VECs) were composited into to form hydrogels. The release of VEGF from hydrogel was delayed compared to that from microspheres. The fluorescent imaging confirmed that VECs had a good proliferation into the hydrogels. The hydrogels were injected into necrosis site of the femoral head, the vessels were observed for 2 weeks, the vessels density and mean vessels diameters increased in next 4–6 weeks, followed by increasing new bone formation. These results suggested that injectable VEGF loaded microspheres/hydrogels composites could be applied for vascularization and bone regeneration of femoral head necrosis.