Organ-on-a-chip systems have the potential to revolutionize drug screening and disease modeling through the use of human stem cell-derived cardiomyocytes. The predictive power of these tissue models critically depends on the functional assembly and maturation of human cells that are used as building blocks for organ-on-a-chip systems. To resemble a more adult-like phenotype on these heart-on-a-chip systems, the surrounding micro-environment of individual cardiomyocyte needs to be controlled. Herein, we investigated the impact of four microenvironmental cues: cell seeding density, types and percentages of non-myocyte populations, the types of hydrogels used for tissue inoculation and the electrical conditioning regimes on the structural and functional assembly of human pluripotent stem cell-derived cardiac tissues. Utilizing a novel, plastic and open-access heart-on-a-chip system that is capable of continuous non-invasive monitoring of tissue contractions, we were able to study how different micro-environmental cues affect the assembly of the cardiomyocytes into a functional cardiac tissue. We have defined conditions that resulted in tissues exhibiting hallmarks of the mature human myocardium, such as positive force-frequency relationship and post-rest potentiation.

中文翻译：

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心脏芯片平台中人体心脏组织组装的工程微环境。

通过使用人类干细胞衍生的心肌细胞，器官芯片系统有可能彻底改变药物筛选和疾病建模。这些组织模型的预测能力很大程度上取决于用作芯片器官系统构建块的人类细胞的功能组装和成熟。为了在这些芯片心脏系统上模拟出更接近成人的表型，需要控制单个心肌细胞周围的微环境。在此，我们研究了四种微环境因素的影响：细胞接种密度、非肌细胞群的类型和百分比、用于组织接种的水凝胶类型以及电调节方案对人类多能干细胞衍生的结构和功能组装的影响。心脏组织。利用一种新颖的、塑料的、开放式的心脏芯片系统，该系统能够连续无创地监测组织收缩，我们能够研究不同的微环境因素如何影响心肌细胞组装成功能性心脏。心脏组织。我们已经定义了导致组织表现出成熟人类心肌特征的条件，例如正的力-频率关系和静息后增强。