摘要In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphate-buffered saline.They also demonstrated prolonged and stable release profiles of Mg2+and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg2+and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.