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使用针式打印机“微观绘画装置”进行 3D 人类心脏组织芯片的生物打印及其心脏毒性分析。

Bioprinting 3D human cardiac tissue chips using the pin type printer 'microscopic painting device' and analysis for cardiotoxicity.

机构信息

NTN Corporation, 1578 Higashikaiduka, Iwata, Japan.

Building Block Science Joint Research Chair, Graduate School of Frontier Biosciences,Osaka University, 1-3 Yamadaoka, Suita 565-0871, Japan.

出版信息

Biomed Mater. 2021 Feb 24;16(2):025017. doi: 10.1088/1748-605X/abdbde.

Abstract

In this study, three-dimensional (3D) cardiac tissue constructed using the pin type bioprinter 'microscopic painting device' and layer-by-layer cell coating technique was confirmed to have drug responsiveness by three different analytical methods for cardiotoxicity assay. Recently, increasing attention has been focused on biofabrication to create biomimetic 3D tissue. Although various tissues can be produced in vitro, there are many issues surrounding the stability and reproducibility of the preparation of 3D tissues. Thus, although many bioprinters have been developed, none can efficiently, reproducibly and precisely produce small 3D tissues (μm-mm order) such as spheroids, which are most commonly used in drug development. The 3D cardiac tissue chips were successfully constructed with a similar number of cells as conventional 2D tissue using a pin type bioprinter, and corresponding drug-induced cardiotoxicities were obtained with known compounds that induce cardiotoxicity. The 3D cardiac tissue chips displayed uniform cell density and completely synchronized electrophysiological properties as compared to 2D tissue. The 3D tissues constructed using a pin type bioprinter as a biofabrication device would be promising tools for cardiotoxicity assay as they are capable of obtaining stable and reproducible data, which cannot be obtained by 2D tissue.

摘要

在这项研究中,使用针型生物打印机“微观绘画装置”和逐层细胞涂层技术构建的三维(3D)心脏组织通过三种不同的细胞毒性分析方法证实具有药物反应性。最近,人们越来越关注生物制造来创建仿生 3D 组织。尽管可以在体外生成各种组织,但 3D 组织的制备在稳定性和重现性方面存在许多问题。因此,尽管已经开发出许多生物打印机,但没有一种能够高效、可重复且精确地生产小 3D 组织(μm-mm 级),如最常用于药物开发的球体。使用针型生物打印机成功构建了具有与传统 2D 组织相似数量细胞的 3D 心脏组织芯片,并获得了已知可引起心脏毒性的化合物的相应药物诱导的心脏毒性。与 2D 组织相比,3D 心脏组织芯片显示出均匀的细胞密度和完全同步的电生理特性。作为生物制造设备的针型生物打印机构建的 3D 组织将是心脏毒性测定的有前途的工具,因为它们能够获得稳定和可重复的数据,而这些数据是 2D 组织无法获得的。

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