<p>Critical bone defects continue to pose a critical challenge in clinical settings. Facilitating rapid and thorough vascularization during bone regeneration is advantageous for the repair of substantial bone defects. Presently, the application of carriers to deliver pharmacological agents or growth factors to bone deficiency areas is an effective strategy for promoting vascularization within bone tissue, with the selection of appropriate carriers being of paramount importance. Because of its unique breathing characteristics and flexible framework structure, metal-organic framework (MOF) materials MIL-53(Fe), make promising nanocarrier for delivery applications. This work aimed to investigate the role of MIL-53(Fe) in the neovascularization of bone regeneration and the possible molecular mechanisms. The results validated that MIL-53(Fe) has excellent dispersion stability and biocompatibility. Angiogenic sprouting requires the activation of endothelial tip cells. By increasing the glycolytic activity of endothelial cells through self-assembling glucose, the nanocarrier MIL-53(Fe) markedly increased endothelial tip cell activation and boosted angiogenesis, ultimately encouraging bone repair. Through the Hippo/Yes-associated protein (YAP) pathway, the MIL-53(Fe)@Glucose complex was demonstrated to increase glycolytic activity and enhance activation of tip cell phenotype. This study demonstrated that the nanocarrier MIL-53(Fe) serves as an effective strategy for promoting rapid and sufficient angiogenesis during bone regeneration.</p> Graphical abstract <p></p>