The Research of Bioactive Glass Functionalized Poly (L-Glutamic Acid) Hydrogels Loaded with VEGF in Bone Defect Repair

<b>Objectives</b>: Critical-size bone defects have been a challenge for clinical treatment, and many studies have been devoted to solving this problem. This study developed an inorganic-organic multi-functional composite hydrogel (PLG-g-TA/VEGF/Sr-BGNPs) for synergistic therapy of bone defects.<br/><b>Methodology</b>: Monodisperse Sr-BGNPs were prepared by sol-gel method, PLG-g-TA polymer was synthesized from L-glutamic acid γ-benzyl ester and then grafted with tyramine, and PLG-g-TA hydrogel was prepared by in situ cross-linking under the action of HRP and H₂O₂. PLG-g-TA/VEGF/Sr-BGNPs composite hydrogels were finally prepared by loading Sr-BGNPs and VEGF. The composite hydrogel was conducted with rBMSCs and HUVECs to explore the osteogenic and angiogenic abilities in vitro. A 5 mm diameter cranial bone defect model was surgically constructed in rats, and the composite hydrogel was implanted in situ to investigate its bone repair performance in vivo.<br/><b>Results:</b> The composite hydrogel could be mineralized to form hydroxyapatite, slow the release of functional ions (Si, Ca, B, and Sr) and VEGF, and maintain the alkaline surrounding environment. In vitro experiments showed that the composite hydrogel could promote the proliferation and osteogenic differentiation of rBMSCs, express the most osteogenesis-related genes and proteins, significantly enhance the tube-forming ability of HUVECs, and effectively inhibit the process of osteoblastic differentiation of RANKL-induced Raw 264.7 and the bone resorption ability of osteoclasts. In vivo, results showed that after the implantation of composite hydrogel, osteogenic and angiogenic biomarkers were upregulated compared with no treatment, and the composite hydrogel could effectively promote the repair of bone defects. Meanwhile, the composite hydrogel showed no apparent adverse effects in vitro and in vivo.<br/><b>Conclusion</b>: The multi-functional composite hydrogel significantly accelerates the bone growth in the hydrogel and bone repair in critical bone defects, thus providing an advanced adjuvant therapy candidate for large-segment bone defects. It is a promising artificial renewable bone grafting biomaterial.