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首页> 外文期刊>Biomaterials Science >Induction of hepatocyte functional protein expression by submicronano-patterning substrates to mimic in vivo structures
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Induction of hepatocyte functional protein expression by submicronano-patterning substrates to mimic in vivo structures

机译:亚微米/纳米图案底物诱导肝细胞功能蛋白表达以模拟体内结构

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摘要

To investigate the influence of bio-inspired metallic superficial topography on the cellular behaviour of a hepatocyte cell line, TiO_2 nanopatterns with diversified shapes and heterotropic lateral dimensions were fabricated using electron beam lithography and atomic layer deposition. The dimensional uniformity and shape diversity of the nanopatterns were confirmed using scanning electron microscopy and atomic force microscopy. These topographical nanocues provide good tools for controlling and regulating multiple hepatocellular functions. The expressions of functional proteins such as albumin, transferrin and cytochrome P450 were tested as functional markers. In addition, the change in cellular orientation, cell alignment and native extracellular matrix (ECM) assembly induced by these well-defined nanotopographies were observed. Twelve hours after cell seeding, TiO_2 nanogratings with a lateral dimension of 240 nm showed a higher degree of functional protein expression compared to other nanotopographical substrates and a flat surface. These findings suggest that the TiO_2 surface resembles a hierarchically-extended collagen nanofibrillar surface and could be recognized by hepatocytes, allowing the proper cytoskeletal orientation and cellular integrity. This TiO_2 nanopattern with a specific shape and dimension (240 nm) might therefore emulate ECM biophysical cues, and the intrinsic topography of TiO_2 surfaces might evoke enhanced cellular responses. These unique surfaces could be further exploited for tissue engineering and bioreactor technology.
机译:为了研究生物启发的金属表面形貌对肝细胞系细胞行为的影响,采用电子束光刻和原子层沉积技术制备了具有多种形状和各向同性横向尺寸的TiO_2纳米图案。使用扫描电子显微镜和原子力显微镜确认了纳米图案的尺寸均匀性和形状多样性。这些地形纳米提示为控制和调节多种肝细胞功能提供了良好的工具。测试功能蛋白如白蛋白,转铁蛋白和细胞色素P450的表达作为功能标记。此外,观察到由这些定义良好的纳米形貌引起的细胞定向,细胞排列和天然细胞外基质(ECM)装配的变化。细胞接种后十二小时,与其他纳米形貌基底和平坦表面相比,横向尺寸为240 nm的TiO_2纳米光栅显示出更高程度的功能蛋白表达。这些发现表明,TiO_2表面类似于分层延伸的胶原蛋白纳米原纤维表面,并且可以被肝细胞识别,从而允许适当的细胞骨架取向和细胞完整性。因此,具有特定形状和尺寸(240 nm)的TiO_2纳米图案可能会模仿ECM生物物理线索,并且TiO_2表面的固有形貌可能引起增强的细胞反应。这些独特的表面可进一步用于组织工程和生物反应器技术。

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