Oliveira Mariana B, Mano João F
Department of Chemistry, CICECO - Aveiro Institute of Materials, Aveiro, Portugal.
Methods Mol Biol. 2018;1771:11-26. doi: 10.1007/978-1-4939-7792-5_2.
The use of patterned platforms to print cellular arrays enables the high-throughput study of cell behavior under a multitude of different conditions. This rapid, cost-saving and systematic way of acquiring biologically relevant information has found application in diverse scientific and industrial fields. In an initial stage of development, platforms targeting high-throughput cellular studies were restricted to standard two-dimensional (2D) setups. The design of novel platforms compatible with three-dimensional (3D) cell culture arose after the elucidation of the extreme importance of culturing cells in matrices resembling the native extracellular matrix-cells and cell-cell interactions. This need for biomimetic environments has been established in fields like drug discovery and testing, disease model development, and regenerative medicine. Here, we provide a description of the processing of flat platforms based on wettability contrast, compatible with the high-throughput generation and study of cell response in 3D biomaterials, including cell-laden hydrogels and porous 3D scaffolds. The application of the aforementioned platforms to produce 3D microtissues, which may find application as tissue models for drug screening or as biomimetic building blocks for tissue engineering, is also addressed. In this chapter, a description of the steps for (1) high-throughput platform processing, (2) deposition of cell and biomaterial arrays, and (3) image-based results screening is provided.
使用图案化平台打印细胞阵列能够在多种不同条件下对细胞行为进行高通量研究。这种获取生物学相关信息的快速、节省成本且系统的方法已在不同的科学和工业领域得到应用。在发展的初始阶段,针对高通量细胞研究的平台局限于标准的二维(2D)设置。在阐明了在类似于天然细胞外基质的基质中培养细胞对于细胞与细胞间相互作用的极端重要性之后,出现了与三维(3D)细胞培养兼容的新型平台设计。在药物发现与测试、疾病模型开发以及再生医学等领域,对仿生环境的这种需求已经确立。在此,我们描述基于润湿性对比的平面平台的加工过程,该过程与在3D生物材料(包括载细胞水凝胶和多孔3D支架)中高通量生成和研究细胞反应兼容。还讨论了上述平台在生产3D微组织方面的应用,这些3D微组织可作为药物筛选的组织模型或组织工程的仿生构建块。在本章中,提供了关于(1)高通量平台加工、(2)细胞和生物材料阵列沉积以及(3)基于图像的结果筛选步骤的描述。