A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical‐Size Bone Regeneration

Abstract Critical‐size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic–organic multifunctional composite hydrogel denoted as PLG‐g‐TA/VEGF/Sr‐BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis‐related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube‐forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa‐B ligand (RANKL)‐induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel‐associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large‐segment bone defects.