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开发一种微流控平台,集成高分辨率微结构生物材料,以研究细胞-材料相互作用。

Development of a microfluidic platform integrating high-resolution microstructured biomaterials to study cell-material interactions.

机构信息

Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, Overijssel, The Netherlands.

出版信息

Lab Chip. 2017 Nov 21;17(23):4134-4147. doi: 10.1039/c7lc00802c.

Abstract

Microfluidic screening platforms offer new possibilities for performing in vitro cell-based assays with higher throughput and in a setting that has the potential to closely mimic the physiological microenvironment. Integrating functional biomaterials into such platforms is a promising approach to obtain a deeper insight into the interactions occurring at the cell-material interface. The success of such an approach is, however, largely dependent on the ability to miniaturize the biomaterials as well as on the choice of the assay used to study the cell-material interactions. In this work, we developed a microfluidic device, the main component of which is made of a widely used biocompatible polymer, polylactic acid (PLA). This device enabled cell culture under different fluidic regimes, including perfusion and diffusion. Through a combination of photolithography, two-photon polymerization and hot embossing, it was possible to microstructure the surface of the cell culture chamber of the device with highly defined geometrical features. Furthermore, using pyramids with different heights and wall microtopographies as an example, adhesion, morphology and distribution of human MG63 osteosarcoma cells were studied. The results showed that both the height of the topographical features and the microstructural properties of their walls affected cell spreading and distribution. This proof-of-concept study shows that the platform developed here is a useful tool for studying interactions between cells and clinically relevant biomaterials under controlled fluidic regimes.

摘要

微流控筛选平台为进行高通量的基于细胞的体外分析提供了新的可能性,并且有可能更接近地模拟生理微环境。将功能生物材料整合到这些平台中是获得对细胞-材料界面相互作用更深入了解的一种很有前途的方法。然而,这种方法的成功在很大程度上取决于将生物材料小型化的能力,以及用于研究细胞-材料相互作用的分析方法的选择。在这项工作中,我们开发了一种微流控设备,其主要部件由一种广泛使用的生物相容性聚合物聚乳酸(PLA)制成。该设备允许在不同的流体状态下进行细胞培养,包括灌注和扩散。通过光刻、双光子聚合和热压印的结合,有可能用高度定义的几何特征微结构化器件的细胞培养室的表面。此外,以不同高度和壁微形貌的金字塔为例,研究了人 MG63 骨肉瘤细胞的粘附、形态和分布。结果表明,形貌特征的高度和其壁的微结构特性都影响细胞的铺展和分布。这项概念验证研究表明,这里开发的平台是在受控流体状态下研究细胞与临床相关生物材料之间相互作用的有用工具。

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