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4659 |
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Thursday, May 12, 2016, Room 3E 2:40 PM Medical Industry |
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Synergistic effect of macro/nano-topography on cytoskeletal distribution leading to improved cell differentiation through ROCK-related signaling pathway |
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Kai Li / Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai Houhua Pan* / Shanghai Institute of Ceramics, Chinese Academy of Sciences, China Youtao Xie/ Shanghai Institute of Ceramics, Chinese Academy of Sciences, China Xuebin Zheng/ Shanghai Institute of Ceramics, Chinese Academy of Sciences, China Tingting Tang/ Shanghai Ninth Peoples Hospital, Shanghai JiaoTong University School of Medicine, China |
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Plasma sprayed titanium coating (TPS) with rough macroporous structure is one of the modification technology commonly used on orthopedic implants. However, owing to the passive bioactivity of Ti, problems still exist when considering the poor early cell responses. Nano-textured surface has been considered as a effective approach to inducing osteogenesis, which has also been utilized for the further bioactive improvement of TPS. However, less attention has been paid to the detailed process of cell-surface interaction on macro/nano surfaces and the following intracellular signaling pathway. In our study, focus has been put on the correlation between cell adhesion behaviors and cell differentiation performance on different surfaces especially the detailed signalling pathway. Nanowire titanium (NT) has been produced by hydrothermal method and introduced onto TPS to obtain the hierarchical macropore/nanowire structure (NTPS). In general, nanowire was beneficial for filopodia generation and cell spreading, while TPS surface could induce the cells to adapt to the rough macroporous topography but poor spreading could be found. Synergistic effect was obtained on hierarchical NTPS surface, with better cell spreading attributed to nanotexture and multi-dimentional cytoskeleton distribution brought by rough macroporous structure. Accordingly, NTPS contributes most to cell differentiation. For the detailed mechanism, western blotting results showed moderate Rho-associated kinase (ROCK) activity on NT and TPS but highest on NTPS. FAK and ERK, were then examined and maximum expression were also observed on NTPS. The following ROCK inhibition down-regulated FAK and ERK expression as well as impeded cell differentiation and difference between all groups diminished. Further FAK inhibition also caused reduced ERK activity and suppressed cell differentiation. It can be concluded that the best performance of NTPS in promoting cell differentiation attributes to the synergistic effect of macro/nano-topography on cytoskeletal distribution, which leads to highest ROCK activity and following downstream FAK-ERK signalling pathway. |