Biomimetic management of bone healing stages: MOFs induce tunable degradability and enhanced angiogenesis-osteogenesis coupling

K Gai and TR Zhang and ZY Xu and GZ Li and ZH He and SH Meng and YX Shi and YH Zhang and Z Zhu and XB Pei and J Wang and QB Wan and H Cai and YJ Li and JY Chen, CHEMICAL ENGINEERING JOURNAL, 493, 152296 (2024).

DOI: 10.1016/j.cej.2024.152296

Currently, biodegradable biomaterials are extensively used in bone regeneration. Nevertheless, a significant challenge remains in accurately adjusting their degradation rates to match bone healing stages to achieve bone regeneration. Herein, we present a novel biodegradable bone grafts integrated with zeolite imidazole framework8 (ZIF-8) nanocrystals, fabricated via microinjection molding. Apart from the reinforcing effect derived from the in situ fibrillation of PCL in PLGA, nanoscale ZIF-8 is inspiringly demonstrated to control the PLGA degradation. Both molecular dynamic simulation and experimental results indicate that Zn 2 + derived from ZIF-8 nanocrystals acts as a Lewis acid to participate the degradation of PLGA matrix, thus successfully reconciles the contradiction between degradation of matrix and maintenance of reinforcing phase. Moreover, nanometric ZIF-8 modified bone grafts improve the angiogenesis-osteogenesis coupling. In vitro , it directly boosts HIF-1 alpha and capillary -like network formation of endothelial cells (ECs), and RUNX2 and OCN expression in bone marrow mesenchymal stem cells (BMSCs). In vivo , bone grafts with a moderate concentration (0.5 %) of ZIF-8 nanoparticles aid vascularized bone regeneration by tunable biodegradation matching bone healing stages. Further, RNA sequencing shows PLGA/PCL@nZ bone grafts promote angiogenesis-osteogenesis by cooperatively regulating calcium signaling pathway in both ECs and BMSCs. Collectively, this study delineates a groundbreaking bone repair strategy with profound clinical application potential.

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