文献类型：期刊文献

英文题名：Tunable and Controlled Release of Cobalt Ions from Metal-Organic Framework Hydrogel Nanocomposites Enhances Bone Regeneration

作者：Sun, Yi[1];Liu, Xuanzhe[1];Zhu, Yu[1];Han, Yue[2];Shen, Junjie[1];Bao, Bingbo[1];Gao, Tao[1];Lin, Junqing[1];Huang, Tengli[1];Xu, Jia[1];Chai, Yimin[1];Zheng, Xianyou[1]

机构：[1]Shanghai Jiao Tong Univ, Dept Orthoped Surg, Peoples Hosp 6, Shanghai 200233, Peoples R China;[2]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai 200237, Peoples R China

年份：2021

卷号：13

期号：49

起止页码：59051

外文期刊名：ACS APPLIED MATERIALS & INTERFACES

收录：;EI(收录号：20215011315717);WOS:【SCI-EXPANDED(收录号:WOS:000752977200078)】；

基金：This research was supported by grants from the National Natural Science Foundation of China (nos. 81930069, 81772338, 81974331, and 81802156) and by the Major Scientific Research and Innovation Project of Shanghai Municipal Education Commission (2019-01-07-00-02E00043).

语种：英文

外文关键词：metal-organic framework; linker doping; cobalt ions; controlled release; bone regeneration

摘要：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 hydrogel has strong therapeutic potential as a desirable Co-ion controlled release system and a powerful proangiogenic/osteogenic agent for the treatment of bone defects.