本研究使用軟蝕刻(soft lithography)技術，將微溝槽轉印在聚二甲基矽氧烷(polydimethalsiloxane，PDMS)薄膜上，同心圓的中心至邊緣的溝槽寬度由20 m至1 m遞減，深度維持在0.8 μm，並藉由低溫氬離子電漿改質，將疏水性的PDMS改質為親水性。本研究選用兩種能表現骨分化能力的細胞：骨母細胞(7F2)與類骨細胞(UMR)培養在親、疏水性以及微溝槽結構的表面，探討貼附(attachment)、細胞排列比率(alignment)、延伸度(elongation)、細胞研展面積(spreading)、增生(proliferation)、細胞骨架分佈(cytoskeleton distribution)、細胞硬度(cell stiffness)及細胞分化(cell differentiation)進行分析。實驗結果顯示，骨母細胞與類骨細胞的排列比率、延伸度與細胞骨架的訊號表現隨著溝槽寬度減少而增加，因此兩種細胞皆具有contact guidance的現象。此外，藉由細胞骨架免疫染色顯示，細胞雙極結構(bipolar)所產生的偽足及肌動蛋白絲具有高度方向性並順著溝槽方向生長，且肌動蛋白絲的密度也會隨溝槽寬度變窄而增加。
在細胞的貼附與細胞增生的結果中，儘管在溝槽寬度為1-6 μm時可以提供較大的貼附面積，但溝槽結構卻會阻礙骨母細胞貼附、延展和增生；反之，此類表面卻會促進類骨細胞的貼附、延展及增生。並根據分析細胞的穿透深度的結果，細胞生長在為溝槽結構時的細胞貼附行為，與細胞本身的軟硬度有絕對的關係，也就是說，類骨細胞能夠研伸進溝槽的底部，所以細胞生長在狹窄的溝槽時能夠促進細胞的貼附，相反的，骨母細胞的硬度較高，狹窄的溝槽將會抑制細胞的研展與貼附，而這個結果與分離細胞與基材表面的功相符。此外，骨母細胞的前期骨分化表現會隨著溝槽寬度的減少增加，並且在窄溝槽上的骨母細胞之楊氏系數最大，這個結果證實了狹窄的溝槽基板能夠促進骨分化表現。另一方面，材料表面的潤濕性也會影響材料表面結構對細胞的調節作用，這是因為細胞親和力的增加，細胞很容易辨識並貼附於基材表面地勢，因而在親水性的表面上，細胞的貼附、延展、排列比率及細胞骨架的方向性行為將更加明顯。

In this research, microgrooved topography was transferred to polydimethylsiloxane (PDMS) by using soft lithography method. The width of grooves and ridges varied from 1 μm to 20 μm, while the groove depth was kept about 0.8 μm. By exposing to Argon plasma treatment, PDMS surface changed from hydrophobic into hydrophilic. The two kinds of cells were cultured on the grooved surfaces in this research, including osteoblast-like cells (UMR) and osteoblasts (7F2) which are able to express osteogenic differentiation. The increase in alignment, elongation and the organization of actin filaments with respect to the decrease in groove width indicated that “contact guidance” was found, which appeared in both of UMR and 7F2. On grooved surface, cells adopted bipolar morphology with few lamellipodia and owned highly orientated actin filaments which located along the groove direction. On the other hand, they exhibited meshwork of peripheral actin filament with many lamellipodia when they were cultured on flat surface.
The attachment, spreading and proliferation of 7F2 were retarded by the small groove patterns (1-6 μm) despite this structure could offer a larger specific area. In contrast, narrow grooves promoted the attachment, spreading, and proliferation of UMR. According to the analysis of cell penetration depth, the effect of topography on cells was determined by the cell flexibility. That was, if cells were able to elongate into groove bottom, such as UMR, the narrow grooves would enhance cell attachment and so on. However, for cells with high stiffness, such as 7F2, narrow groove would retard cell spreading and attachment seriously. The results were also identified from the works for cell-PDMS separation.
Furthermore, early osteoblastic differentiation (ALPase) of osteoblast cells was notably enhanced corresponding to the reduction of groove width. The cell stiffness was also enhanced due to the reduction of groove width. This finding confirms that narrow groove patterns are able to promote osteoblasts differentiation. The research outcomes implicate that microgrooved surfaces would promote the orientation and then the differentiation of osteoblasts. On the other hand, the influences of surface wettability were also examined and the results indicate that hydrophilic surface could enhance the effect of groove patterns. Because of the high affinity between cells and hydrophilic surfaces, cultured cells would recognize topographical cues better on grooved PDMS with high wettability.

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