One‐Pot Facile Encapsulation of Dimethyloxallyl Glycine by Nanoscale Zeolitic Imidazolate Frameworks‐8 for Enhancing Vascularized Bone Regeneration

Abstract In the process of bone tissue regeneration, regulation of osteogenesis–angiogenesis coupling is of great importance. Therefore, dimethyloxallyl glycine (DMOG) is loaded by nanoscale zeolitic imidazolate frameworks‐8 (ZIF‐8) to obtain a drug‐loading system that can promote osteogenesis–angiogenesis coupling. Characterization of the drug‐loading nanoparticles (DMOG@ZIF‐8) reveals that DMOG is successfully loaded into ZIF‐8 by two different methods, and the DMOG@ZIF‐8 is prepared using the one‐pot method (OD@ZIF‐8) achieves higher loading efficiency and longer release time than those prepared using the post‐loading method (PD@ZIF‐8). In vitro studies found that DMOG@ZIF‐8 significantly enhances the migration, tube formation, and angiogenesis‐related protein secretion of human umbilical vein endothelial cells as well as the extracellular matrix mineralization, alkaline phosphatase activity, and osteogenesis‐related protein secretion of bone marrow mesenchymal stem cells. Moreover, OD@ZIF‐8 nanoparticles are more efficient than PD@ZIF‐8 nanoparticles in induction of osteogenesis–angiogenesis coupling. Then, in vivo cranial critical defect model shows that the addition of OD@ZIF‐8 significantly promotes vascularized bone formation as indicated by the results including microcomputed tomographic, histological and immunofluorescence staining, and so on. Taken together, loading ZIF‐8 with DMOG may be a promising solution for critical‐sized bone defect reconstruction and the one‐pot method is preferred in the preparation of such drug‐loading system.