Mil-53(Fe)-Glucose Self-Assembled Complex Enhances Vascularization

This study investigates the role of metal-organic framework (MOF) nanomaterial MIL-53(Fe) in bone tissue vascularization and its underlying mechanisms. MIL-53(Fe) was synthesized via hydrothermal reaction and characterized for morphology, phase composition et al. Its biocompatibility as well as its effect on vascularization induction and endothelial tip cell activation was assessed in vitro. A cranial defect model in SD rats (eight weeks old, ranging from 250 g to 300 g) was used to evaluate the pro-angiogenic efficacy via CD31 immunohistochemistry and H-type vessel immunofluorescence staining. Bulk RNA-seq was used to analyze the potential mechanisms regulating vascular formation. Molecular dynamics simulations verified MIL-53(Fe)-glucose self-assembly. Glycolysis in vascular endothelial cells was assessed using glycolysis assays, such as the Seahorse XFe96 metabolic analyzer. MIL-53(Fe) demonstrated good biocompatibility and enhanced efficacy of endothelial tip cell activation and vessel formation. In vivo, it facilitated bone tissue vascularization and H-type vessel formation. The results of bulk RNA-seq, molecular dynamics simulation, and glycolytic activity detection indicated that MIL-53(Fe), self-assembling with glucose molecules, promoted the glycolytic activity of vascular endothelial cells via the Hippo-YAP pathway, which was further confirmed by in vivo experiments. MIL-53(Fe) enhanced glycolysis and endothelial tip cell activation by regulating the Hippo-YAP pathway. This study provides a novel strategy for the selection of optimal delivery carriers for vascularization in bone regeneration.