Hierarchically released biomimetic scaffold incorporating VEGF, bFGF, and BMP2 synergistically promotes angiogenesis and bone regeneration
Nan Wang, Zongxin Li, Xiaoyu Shen, Yaopeng Zhang, Xiang Yao, Yiyang Wang, Jie Hu, Ming Zheng, Qiang Zhou, Jixing Ye
Abstract
Existing bone biomaterials inadequately simulate the intricate natural bone healing signal cascade. This study integrated vascularization and bone formation with a multi-growth factor delivery system to emulate the angiogenesis and osteogenesis signal cascade during bone repair. It was observed that VEGF (vascular endothelial growth factor) primarily stimulated the proliferation, migration, and tube formation of HUVECs (human umbilical vein endothelial cells), while not influencing BMP2 (bone morphogenetic protein 2) induced osteogenic differentiation of MSCs (mesenchymal stem cells). On the other hand, pretreatment of MSCs with low concentration bFGF (basic fibroblast growth factor) for 1 day and subsequent addition of BMP2 enhanced BMP2-induced osteogenic differentiation via regulation of the PI3K/Akt-GSK3β-β-catenin pathway and β-catenin expression and nuclear translocation. Based on these findings, a hierarchically released biomimetic scaffold composed of GelMA (Gelatin methacrylate) microspheres and silk fibroin composite material was fabricated, featuring early release of VEGF and bFGF and sustained release of BMP2. In vivo, osteogenesis and bone repair experiments demonstrated enhanced angiogenesis, osteogenesis, and bone repair capacity of this hierarchically released biomimetic scaffold, indicating promising clinical applications for bone defect repair.