The dimension of TiO₂ nanotubes (TNTs) ranges from several nanometers to hundreds of nanometers. This variety raises the difficulty of screening suitable nanotube dimension for biomedical applications. Herein, we report the use of a simple one-step bipolar anodization method for fabrication of TNT gradients with diameter range from 30 to 100 nm. The gradient TNTs were successfully applied for high-throughput screening of TNT size effect on cell responses, including cell adhesion, proliferation, and differentiation. Results reveal that no significant difference in adherent cell number could be found within the range of 30–87 nm in both the presence and absence of serum proteins. On the contrary, large nanotubes (with outer diameter >87 nm) profoundly reduce cell adhesion in both the presence and absence of serum proteins, indicating TNT size could affect cell adhesion directly without the adsorbed proteins. The size effect on cell behavior becomes prominent with time that cell proliferation and differentiation decrease with increasing nanotube size. This size effect can be comprehended by protein adsorption and the formation of focal adhesion. Another two sample applications of gradient TNTs demonstrate gradient TNTs are promising for high-throughput screening.

中文翻译：

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梯度TiO ₂纳米管对大鼠间充质干细胞行为的高通量筛选

TiO ₂的尺寸纳米管（TNT）的范围从几纳米到几百纳米。该品种增加了筛选适合生物医学应用的纳米管尺寸的难度。在此，我们报告了使用简单的一步双极阳极氧化方法来制造直径范围为30至100 nm的TNT梯度的方法。梯度TNT已成功应用于TNT大小对细胞反应（包括细胞粘附，增殖和分化）的高通量筛选。结果表明，无论是否存在血清蛋白，在30–87 nm范围内均未发现粘附细胞数量的显着差异。相反，在存在和不存在血清蛋白的情况下，大型纳米管（外径> 87 nm）都会大大减少细胞粘附，表明TNT的大小可能会直接影响细胞粘附，而不会吸附蛋白质。随着时间的流逝，尺寸对细胞行为的影响变得显着，细胞增殖和分化随纳米管尺寸的增加而降低。这种尺寸效应可以通过蛋白质吸附和粘着斑的形成来理解。梯度TNT的另外两个示例应用程序证明，梯度TNT对于高通量筛选很有前景。