Although it has been well established that osteogenic differentiation of bone mesenchymal stem cells (bMSCs) as well as osteoclastic differentiation of macrophages can be manipulated by the nanostructure of biomaterial surfaces, the interactions among the effects of the surface on immune cells and bMSCs remained unknown. Therefore, in this study, the osteogenic behaviors and secretion of osteoclastogenesis-related cytokines of human bMSCs on TiO₂ nanotubular (NT) surfaces in conditioned medium (CM) generated by macrophages cultured on the respective NT surfaces (NT-CM) were analyzed. Although bMSCs showed consistent osteogenic behaviors on the NT5 and NT20 surfaces in both standard culture medium and both types of NT-CM, collagen synthesis and extracellular matrix mineralization were partially impeded on the NT20 surface in NT20-CM and bMSC cytokine secretions on the NT20 surface in NT20-CM elicited remarkable multinuclear giant cell and osteoclast formation compared with that observed on the NT5 surface in NT5-CM. After implantation in vivo, mineralized bone formation was significantly delayed around the NT20 implant compared with the NT5 implant, but both surfaces contributed to good bone formation after 12 weeks. The results obtained in this study advance our understanding of the confounding influence of the implant surface nanostructure, macrophage inflammatory response, and osteogenic differentiation of bMSCs as well as the retro-regulative effects of bMSCs on the osteoclastic differentiation of macrophages, and the culture system based on different NT surfaces and CM generated on the respective surfaces may provide a systematic research model for evaluating the performance of endosseous implants as well as a prospective approach for improving implant osseointegration via immune-regulation.

中文翻译：

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响应巨噬细胞介导的炎症反应的sRANKL / OPG / M-CSF的骨间充质干细胞分泌影响纳米结构Ti表面的成骨作用

尽管已经公认可以通过生物材料表面的纳米结构来操纵骨间充质干细胞（bMSCs）的成骨分化以及巨噬细胞的破骨细胞分化，但是该表面对免疫细胞和bMSCs的作用之间的相互作用仍然未知。因此，在这项研究中，人bMSCs在TiO ₂上的成骨行为和破骨细胞生成相关细胞因子的分泌分析了在相应NT表面（NT-CM）上培养的巨噬细胞在条件培养基（CM）中产生的纳米管（NT）表面。尽管bMSCs在两种标准培养基和两种类型的NT-CM中均在NT5和NT20表面上表现出一致的成骨行为，但在NT20-CM的NT20表面上胶原合成和细胞外基质矿化受到部分阻碍，而在NT20表面上的bMSC细胞因子分泌与在NT5-CM中在NT5表面上观察到的相比，NT20-CM中的α-淀粉酶诱导了显着的多核巨细胞和破骨细胞形成。在体内植入后，与NT5植入物相比，NT20植入物周围矿化的骨形成明显延迟，但是12周后两个表面均有助于良好的骨形成。