細胞在奈米/次微米溝槽表面的行為研究

利用細胞周圍微環境的物理因素，例如材料表面地形，調控細胞的生長和分化行為對於生醫裝置、人體植入物、和組織工程的應用具有重要的影響。物理刺激，例如細胞貼附在具有溝槽的表面，已經證實對於細胞表現具有不同生物程度的影響。本論文的目地為瞭解不同尺寸的微/奈米溝槽表面地形，對於骨骼肌肉細胞、心肌細胞、與間葉幹細胞生長與分化的影響。結果顯示，微/奈米溝槽表面對於三種細胞的排列有顯著的影響，其主要受到溝槽深度的支配，而並非寬度。骨骼肌肉細胞在溝槽表面產生順延後，肌小管融合指數比在平坦表面高，推斷是由於平行排列的骨骼肌肉細胞增加了頭尾相接的機會，進而促進融合行為。而將溝槽表面接枝胜肽後，不但產生平行的肌小管，也提升了整體肌小管融合指數。心肌細胞在溝槽表面產生順延後，細胞的收縮速率較平坦表面高，推斷是由於平行排列的心肌細胞收縮的方向較一致，力量不會互相抵銷導致。而將溝槽表面轉印在較柔軟的材料上，可以延長心肌細胞的收縮功能，證明地形與材料硬度均很重要。間葉幹細胞在微/奈米溝槽表面產生順延後，生長速率和硬骨分化的程度並沒有顯著的改變。但是，對於早期肌肉分化與脂肪分化，在溝槽表面均要比在平坦表面要高。化學的因子與物理的溝槽地形均會對間業幹細胞的分化產生影響，但前者的效應可能更大。本研究證實，微/奈米溝槽表面改變了細胞貼附行為、細胞型態、細胞分化、與細胞的功能。本研究的結果，希望能對於生醫材料的設計、細胞生理學、與組織工程的發展有所幫助。

關鍵字

微/奈米溝槽地形；平行排列；骨骼肌肉；心肌；間葉幹細胞；硬骨/脂肪/肌肉分化

並列摘要

Directing mammalian cell behavior using biophysical cues such as topography in the extracellular microenvironment is crucial for the successes in the biomedical devices, implants, and tissue engineering. It has been suggested that groove/ridge topography modulate cellular behaviors in different biological level. The goal of this dissertation is to understand the effect of nano/submicron grooved surface on the behaviors of skeletal myoblasts, cardiomyocytes, and rat mesenchymal stem cells (rMSCs). Nano/submicron grooved surfaces affect focal adhesion, cell alignment, and function of cell in a remarkable manner, dominating by the depth of groove. Myogenic index of aligned skeletal myoblasts is enhanced on the grooved surfaces compared to the flat control, due to increase in the end-to-end fusion. Peptide conjugation further enhances the myogenic index and meantime morphologically parallel myotubes. The contractile function of aligned cardiomyocytes is upregulated on the grooved surface compared to the flat control, because the anisotropic morphology facilitates synchronous contraction of cardiomyocytes. The rigidity of substrate also affects the contraction of cardiomyocytes. Grooved surfaces have minor effect on cell proliferation and osteogenesis of rMSCs compared to the flat control, while these surfaces enhance the early myogenesis and adipogenesis of rMSCs. Chemical factor and topographic cue both affect the rMSCs differentiation, while the former plays a more momentous role. Taken together, nano/submicron grooved surface modulated focal adhesion and cell morphology anisotropically, depending on the feature size, which in turn changes the differentiation and functionality of cells in a cell-type dependent manner.

並列關鍵字

grooved topography ； anisotropic ； alignment ； stem cells ； differentiation

參考文獻

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國際替代計量

細胞在奈米/次微米溝槽表面的行為研究

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