Petronis Sarunas, Gretzer Christina, Kasemo Bengt, Gold Julie
Department of Applied Physics, Chalmers University of Technology, SE 412 96 Gothenburg, Sweden.
J Biomed Mater Res A. 2003 Sep 1;66(3):707-21. doi: 10.1002/jbm.a.10056.
A model system for studying cell-surface interactions, based on microfabricated cell culture substrates, has been developed and is described here. Porous surfaces consisting of interconnecting channels with openings of subcellular dimensions are generated on flat, single crystal, silicon substrates. Channel size (width, depth), distribution, and surface coating can be varied independently and used for systematic investigation of how topographical, chemical, and elastic surface properties influence cell or tissue biological responses. Model porous surfaces have been produced by using two different microfabrication methods. Submicron-sized channels with very high depth-to-width aspect ratios (up to 30) have been made by using electron beam lithography and anisotropic reactive ion etching into single-crystal silicon. Another method uses thick-resist photolithography, which can be used to produce channels wider than 1 microm and with depth-to-width aspect ratios below 20 in an epoxy polymer. Preliminary cell culture tests show that fibroblasts bridge 0.8- to 1.8-microm-wide channels with very few exceptions (i.e., a continuous space below the cell-surface interface is created). It has also been shown that variation of channel periodicity significantly affects fibroblast morphology and attachment density. With this model system, it is possible to load the channels with bioactive substances intended to interact with cells at or near the surface in a time-dependent manner.
基于微加工细胞培养底物开发了一种用于研究细胞表面相互作用的模型系统，本文对此进行了描述。在平坦的单晶硅基板上生成由具有亚细胞尺寸开口的相互连接通道组成的多孔表面。通道尺寸（宽度、深度）、分布和表面涂层可以独立变化，并用于系统研究地形、化学和弹性表面特性如何影响细胞或组织的生物学反应。已通过两种不同的微加工方法制备了模型多孔表面。通过使用电子束光刻和对单晶硅进行各向异性反应离子蚀刻，制造出了具有非常高的深宽比（高达30）的亚微米级通道。另一种方法使用厚抗蚀剂光刻技术，可用于在环氧聚合物中制造宽度大于1微米且深宽比低于20的通道。初步细胞培养测试表明，成纤维细胞跨越0.8至1.8微米宽的通道，极少有例外情况（即细胞表面界面下方形成连续空间）。还表明通道周期性的变化会显著影响成纤维细胞的形态和附着密度。利用该模型系统，可以在通道中加载旨在以时间依赖性方式与表面或表面附近的细胞相互作用的生物活性物质。
