miR-21 promotes osseointegration and mineralization through enhancing both osteogenic and osteoclastic expression
miR-21 promotes osseointegration and mineralization through enhancing both osteogenic and osteoclastic expression
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miR-21 通过增强成骨细胞和破骨细胞的表达来促进骨整合和矿化
DOI：
10.1016/j.msec.2020.110785
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发表时间：
2020-06-01
影响因子：
7.9
通讯作者：
Liu, Changsheng
中科院分区：
文献类型：
--
作者：
Geng, Zhen;Yu, Yuanman;Liu, Changsheng
随着人口老龄化，对骨科植入物的需求持续增加。钛及钛合金作为应用最广泛的骨科材料，取得了很高的成功率。然而，缺乏骨组织整合仍然是手术成功的障碍。在这项研究中，钛表面的酸处理和功能化的miR-21纳米帽通过原位聚合方法。该涂层显示出均匀的miR-21分布和可持续的miR-21释放。体外研究表明，miR-21不仅能促进MSCs向成血管和成骨细胞分化，而且能增强MSCs的成骨活性。此外，体内评价，包括X射线、显微CT、组织学、免疫组织化学、生物力学测试、拉曼和SEM-EDS，表明微粗糙表面可以增加骨-种植体接触，从而改善早期阶段的骨整合。更重要的是，miR-21纳米帽涂层加速了血管化（CD 31的高表达）、骨重建（成骨和破骨细胞相关蛋白的高表达）和骨成熟（高比例的磷灰石），从而显著改善了骨-植入物接触并增强了骨-植入物结合强度（1个月时是Ti的两倍）。这些结果表明，钛基微粗糙表面功能化的miR-21纳米帽在骨科领域有潜在的应用。
The demand for orthopedic implants continues to increase with the aging population. As the most widely used orthopedic materials, titanium and its alloys have achieved high success rates. However, the lack of bone tissue integration remains a barrier to successful operations. In this study, the titanium surface was acid-treated and functionalized with miR-21 nanocapsules via an in situ polymerization method. This coating showed a uniform miR-21 distribution and sustainable miR-21 release. The in vitro studies indicated that miR-21 could not only promote angiogenic and osteogenic differentiation of MSCs but also enhance osteoclastic activity. Additionally, in vivo evaluations, including X-ray, micro-CT, histology, immunohistochemistry, biomechanical testing, Raman and SEM-EDS, demonstrated that the micro-rough surface could increase the bone-implant contact and, thus, improved osseointegration during the early stages. More importantly, the miR-21 nanocapsule coating accelerated vascularization (high expression of CD31), bone remodeling (high expression of both osteogenesis- and osteoclast-related proteins) and bone maturation (high proportion of apatite), resulting in a significantly improved bone-implant contact and enhanced bone-implant bonding strength (twice the Ti at 1 month). These results indicated that a Ti-based micro-rough surface functionalized with miR-21 nanocapsules had potential applications in the orthopedic field.