Schneider Oliver, Moruzzi Alessia, Fuchs Stefanie, Grobel Alina, Schulze Henrike S, Mayr Torsten, Loskill Peter
Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, Germany.
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
Mater Today Bio. 2022 May 7;15:100280. doi: 10.1016/j.mtbio.2022.100280. eCollection 2022 Jun.
Over the last decade, Organ-on-Chip (OoC) emerged as a promising technology for advanced models, recapitulating key physiological cues. OoC approaches tailored for cardiac tissue engineering resulted in a variety of platforms, some of which integrate stimulation or probing capabilities. Due to manual handling processes, however, a large-scale standardized and robust tissue generation, applicable in an industrial setting, is still out of reach. Here, we present a novel cell injection and tissue generation concept relying on spheroids, which can be produced in large quantities and uniform size from induced pluripotent stem cell-derived human cardiomyocytes. Hydrostatic flow transports and accumulates spheroids in dogbone-shaped tissue chambers, which subsequently fuse and form aligned, contracting cardiac muscle fibers. Furthermore, we demonstrate electrical stimulation capabilities by utilizing fluidic media connectors as electrodes and provide the blueprint of a low-cost, open-source, scriptable pulse generator. We report on a novel integration strategy of optical O sensor spots into resin-based microfluidic systems, enabling determination of O partial pressures. Finally, a proof-of-concept demonstrating electrical stimulation combined with monitoring of metabolic activity in cardiac tissues is provided. The developed system thus opens the door for advanced OoCs integrating biophysical stimulation as well as probing capabilities and serves as a blueprint for the facile and robust generation of high density microtissues in microfluidic modules amenable to scaling-up and automation.
在过去十年中，芯片器官（OoC）作为一种用于先进模型的有前途的技术出现，可概括关键生理线索。为心脏组织工程量身定制的OoC方法产生了多种平台，其中一些集成了刺激或探测功能。然而，由于手动处理过程，在工业环境中适用的大规模标准化且稳健的组织生成仍然无法实现。在此，我们提出一种依赖球体的新型细胞注射和组织生成概念，该球体可由诱导多能干细胞衍生的人类心肌细胞大量生产且尺寸均匀。静水压流将球体运输并聚集在狗骨形组织腔室中，随后球体融合并形成排列整齐、收缩的心肌纤维。此外，我们通过利用流体介质连接器作为电极展示了电刺激能力，并提供了一种低成本、开源、可编写脚本的脉冲发生器的蓝图。我们报告了一种将光学氧传感器点集成到基于树脂的微流控系统中的新型策略，能够测定氧分压。最后，提供了一个概念验证，展示了心脏组织中的电刺激与代谢活性监测相结合。因此，所开发的系统为集成生物物理刺激以及探测功能的先进OoC打开了大门，并为在适合扩大规模和自动化的微流控模块中轻松、稳健地生成高密度微组织提供了蓝图。
