Iron-based metal–organic framework as a dual cooperative release system for enhanced vascularization and bone regeneration

Vascularization and bone regeneration are closely related in the process of bone remodeling, and designing a bioactive scaffold with pro-angiogenic and osteogenic properties may accelerate the repair of bone defects. In this work, an iron-based metal–organic framework (MIL-88) was developed as a carrier for loading a pro-angiogenic small molecular drug (dimethyloxallyl glycine, DMOG), and then embedded into the PLGA nanofibrous scaffolds to repair cranial defects in rats. Imaging and histological evaluation indicated that PLGA/MIL@D scaffold markedly enhanced vascularization and bone regeneration in vivo. Moreover, in vitro assay showed that co-delivery system significantly promoted angiogenesis by stimulating endothelial cell migration, tube formation, and enhanced osteogenesis by promoting expression of osteoblast related proteins. In addition, PLGA/MIL@D scaffold promotes angiogenesis by activating the hypoxia-inducible factor-1 (HIF-1)/vascular endothelial growth factor (VEGF) signaling pathway. Altogether, this bioactive PLGA/MIL@D scaffold can combine angiogenesis with osteogenesis, and will be a bright strategy for the repair of bone defects.