Recent advances in microarray 3D bioprinting for high-throughput spheroid and tissue culture and analysis.
Recent advances in microarray 3D bioprinting for high-throughput spheroid and tissue culture and analysis.
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DOI：
10.1042/ebc20200150
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发表时间：
2021-08-10
影响因子：
6.4
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体外三维（3D）细胞培养已被证明比细胞单层的二维（2D）培养更具有生理学相关性，因此在评估化合物的功效和毒性方面更具预测性。已经开发了几种3D细胞培养技术，包括球体和多细胞组织培养。细胞球状体已经由在超低附着（ultralow attachment，贴壁）孔板和悬滴板中培养的单个或多个细胞类型产生。通常，细胞球状体在相对短的培养时间内，在不存在细胞外基质（ECM）的情况下，通过重力驱动的自聚集形成，因此在分层结构中具有有限的自组织能力。另一方面，包括源自多能干细胞和成体干细胞（a.k.a.生物打印组织构建体（例如，“类器官”）和3D生物打印组织构建体需要仿生水凝胶或ECM，并且由于细胞在分化和成熟过程中的自发自组织而显示出高度有序的结构。在这篇简短的综述文章中，我们总结了球体和多细胞组织培养的传统方法及其技术挑战，并介绍了如何使用基于液滴的微型3D生物打印（“微阵列3D生物打印”）来提高测定通量和重现性，以进行高通量，预测性的化合物筛选。介绍了几种平台，包括微柱芯片和384柱板，用于通过微阵列3D生物打印促进微型球体和组织培养。我们排除了微生理系统（MPS）在这篇文章中，虽然他们是重要的组织模型，以模拟多器官相互作用。
Three-dimensional (3D) cell culture in vitro has proven to be more physiologically relevant than two-dimensional (2D) culture of cell monolayers, thus more predictive in assessing efficacy and toxicity of compounds. There have been several 3D cell culture techniques developed, which include spheroid and multicellular tissue cultures. Cell spheroids have been generated from single or multiple cell types cultured in ultralow attachment (ULA) well plates and hanging droplet plates. In general, cell spheroids are formed in a relatively short period of culture, in the absence of extracellular matrices (ECMs), via gravity-driven self-aggregation, thus having limited ability to self-organization in layered structure. On the other hand, multicellular tissue cultures including miniature tissues derived from pluripotent stem cells and adult stem cells (a.k.a. ‘organoids’) and 3D bioprinted tissue constructs require biomimetic hydrogels or ECMs and show highly ordered structure due to spontaneous self-organization of cells during differentiation and maturation processes. In this short review article, we summarize traditional methods of spheroid and multicellular tissue cultures as well as their technical challenges, and introduce how droplet-based, miniature 3D bioprinting (‘microarray 3D bioprinting’) can be used to improve assay throughput and reproducibility for high-throughput, predictive screening of compounds. Several platforms including a micropillar chip and a 384-pillar plate developed to facilitate miniature spheroid and tissue cultures via microarray 3D bioprinting are introduced. We excluded microphysiological systems (MPSs) in this article although they are important tissue models to simulate multiorgan interactions.