Tunable and Controlled Release of Cobalt Ions from Metal–Organic Framework Hydrogel Nanocomposites Enhances Bone Regeneration

作者：Yi Sun, Xuanzhe Liu, Yu Zhu, Yue Han, Junjie Shen, Bingbo Bao, Tao Gao, Junqing Lin, Tengli Huang, Jia Xu, Yimin Chai, Xianyou Zheng · 发表于：ACS Applied Materials & Interfaces · 年份：2021 · DOI：10.1021/acsami.1c16300 · 被引用次数：80 · 研究领域：Nanoplatforms for cancer theranostics、Bone Tissue Engineering Materials、Mesenchymal stem cell research

Cobalt (Co) ions, which can mimic hypoxia to promote angiogenesis, exhibit great potential for bone repair. However, a key point for the use of Co ions is that their release profile should be controllable and, more importantly, suitable for the bone regeneration process. Here, 2-ethylimidazole (eIm) was introduced into zeolitic imidazolate framework-67 (ZIF-67) to slow down Co-ion release and fabricate eIm-doped ZIF-67 (eIm/ZIF-67), which was combined into gelatin methacrylate (GelMA) to obtain an in situ photo-cross-linking nanocomposite hydrogel as a tunable Co-ion controlled release system. A tunable and controlled release of Co ions from the nanocomposite hydrogel was achieved by variation of linker composition, and GelMA with 75% eIm/ZIF-67 (with 75% eIm in the precursor solutions) could maintain a 21-day sustained release of Co ions, which is matched with early-stage angiogenesis during the bone formation process. Our in vitro study also showed that the GelMA@eIm/ZIF-67 hydrogel could reduce cytotoxicity and effectively promote the angiogenic activity of human umbilical vein endothelial cells (HUVECs) and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Moreover, an in vivo rat calvarial defect model demonstrated that the GelMA@eIm/ZIF-67 hydrogel exhibited remarkably enhanced bone formation and neovascularization abilities and had good biocompatibility as shown in organ histopathological examinations. Therefore, this novel nanocomposite hydroge...