Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, P. R. China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
ACS Biomater Sci Eng. 2020 Feb 10;6(2):969-983. doi: 10.1021/acsbiomaterials.9b01717. Epub 2020 Jan 23.
The success of orthopedic implants requires rapid and complete osseointegration which relies on an implant surface with optimal features. To enhance cellular function in response to the implant surface, micro- and nanoscale topography have been suggested as essential. The aim of this study was to identify an optimized Ti nanostructure and to introduce it onto a titanium plasma-sprayed titanium implant (denoted NTPS-Ti) to confer enhanced immunomodulatory properties for optimal osseointegration. To this end, three types of titania nanostructures, namely, nanowires, nanonests, and nanoflakes, were achieved on hydrothermally prepared Ti substrates. The nanowire surface modulated protein conformation and directed integrin binding and specificity in such a way as to augment the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and induce a desirable osteoimmune response of RAW264.7 macrophages. In a coculture system, BMSCs on the optimized micro/nanosurface exerted enhanced effects on nonactivated or lipopolysaccharide-stimulated macrophages, causing them to adopt a less inflammatory macrophage profile. The enhanced immunomodulatory properties of BMSCs grown on NTPS-Ti depended on a ROCK-medicated cyclooxygenase-2 (COX2) pathway to increase prostaglandin E2 (PGE2) production, as evidenced by decreased production of PGE2 and concurrent inhibition of immunomodulatory properties after treatment with ROCK or COX2 inhibitors. evaluation showed that the NTPS-Ti implant resulted in enhanced osseointegration compared with the TPS-Ti and Ti implants. The results obtained in our study may provide a prospective approach for enhancing osseointegration and supporting the application of micro/nanostructured Ti implants.
骨科植入物的成功需要快速且完全的骨整合，这依赖于具有最佳特性的植入物表面。为了增强细胞对植入物表面的功能，已经提出微纳尺度形貌是必不可少的。本研究的目的是确定优化的 Ti 纳米结构，并将其引入钛等离子喷涂钛植入物（表示为 NTPS-Ti）中，以赋予增强的免疫调节特性，从而实现最佳的骨整合。为此，在水热制备的 Ti 基底上实现了三种类型的二氧化钛纳米结构，即纳米线、纳米巢和纳米片。纳米线表面调节蛋白质构象，并以增强整合素结合和特异性的方式引导，从而增强骨髓间充质干细胞（BMSCs）的成骨分化，并诱导 RAW264.7 巨噬细胞产生理想的骨免疫反应。在共培养系统中，优化的微/纳表面上的 BMSCs 对非激活或脂多糖刺激的巨噬细胞施加了增强的作用，使它们采用较少炎症的巨噬细胞表型。BMSCs 在 NTPS-Ti 上生长的增强的免疫调节特性取决于 ROCK 介导的环氧化酶-2（COX2）途径，以增加前列腺素 E2（PGE2）的产生，这表现在使用 ROCK 或 COX2 抑制剂处理后，PGE2 的产生减少和同时抑制免疫调节特性。评价表明，与 TPS-Ti 和 Ti 植入物相比，NTPS-Ti 植入物导致增强的骨整合。我们研究中获得的结果可能为增强骨整合和支持微/纳结构 Ti 植入物的应用提供一种有前景的方法。
