VEGF-loaded biomimetic scaffolds: a promising approach to improve angiogenesis and osteogenesis in an ischemic environment

Abstract

The treatment of bone defects in an ischemic environment is a huge challenge. Improving angiogenesis, which is regulated by angiogenic growth factors such as vascular endothelial growth factor (VEGF), may have the potential to enhance bone regeneration. This study was conducted to investigate whether VEGF-loaded biomimetic scaffolds could improve angiogenesis and osteogenesis in an ischemic limb. The biomimetic hydroxyapatite–collagen scaffold (HC scaffold) was fabricated by adopting the freeze-drying approach. In the HC-VEGF group, VEGF was incorporated into HC scaffolds. The cytocompatibility of the HC scaffold was evaluated by CCK-8 testing. The release profile of VEGF from the HC-VEGF scaffold was detected by using VEGF ELISA kits. The femoral artery of Sprague-Dawley rats was resected to induce an ischemic environment. HC scaffolds with or without VEGF were implanted into intramuscular pockets in the ischemic limb. Eight weeks after implantation, samples were retrieved for histological and immunohistochemical analysis. The HC scaffolds showed good cytocompatibility according to the results of a CCK-8 test. In vitro, an initial burst release (∼80%) of VEGF was detected during the first 3 days. Angiogenesis and osteogenesis were significantly enhanced in the HC-VEGF group, compared to the control group of HC scaffolds without VEGF. This study provided a very promising approach to enhance angiogenesis and osteogenesis in an ischemic environment by incorporating VEGF into biomimetic bone scaffolds.