Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Institute for Complex Molecular Systems (ICMS), Eindhoven, The Netherlands.
Tissue Eng Part C Methods. 2021 Mar;27(3):139-151. doi: 10.1089/ten.TEC.2020.0342. Epub 2021 Mar 5.
cardiac modeling has taken great strides in the past decade. While most cell and engineered tissue models have focused on cell and tissue contractile function as readouts, mechanobiological cues from the cell environment that affect this function, such as matrix stiffness or organization, are less well explored. In this study, we review two-dimensional (2D) and three-dimensional (3D) models of cardiac function that allow for systematic manipulation or precise control of mechanobiological cues under simulated (patho)physiological conditions while acquiring multiple readouts of cell and tissue function. We summarize the cell types used in these models and highlight the importance of linking 2D and 3D models to address the multiscale organization and mechanical behavior. Finally, we provide directions on how to advance modeling for cardiac mechanobiology using next generation hydrogels that mimic mechanical and structural environmental features at different length scales and diseased cell types, along with the development of new tissue fabrication and readout techniques. Impact statement Understanding the impact of mechanobiology in cardiac (patho)physiology is essential for developing effective tissue regeneration and drug discovery strategies and requires detailed cause-effect studies. The development of three-dimensional models allows for such studies with high experimental control, while integrating knowledge from complementary cell culture models and studies for this purpose. Complemented by the use of human-induced pluripotent stem cells, with or without predisposed genetic diseases, these models will offer promising outlooks to delineate the impact of mechanobiological cues on human cardiac (patho)physiology in a dish.
在过去的十年中，心脏建模取得了重大进展。虽然大多数细胞和工程组织模型都侧重于细胞和组织收缩功能作为读出指标，但影响该功能的细胞环境中的机械生物学线索，如基质硬度或组织，研究得较少。在这项研究中，我们回顾了二维（2D）和三维（3D）心脏功能模型，这些模型允许在模拟（病理）生理条件下系统地操纵或精确控制机械生物学线索，同时获取细胞和组织功能的多个读出值。我们总结了这些模型中使用的细胞类型，并强调了将 2D 和 3D 模型联系起来以解决多尺度组织和力学行为的重要性。最后，我们提供了如何使用模拟机械和结构环境特征的下一代水凝胶以及开发新的组织制造和读出技术来推进心脏机械生物学建模的方向。 影响说明 了解机械生物学在心脏（病理）生理学中的影响对于开发有效的组织再生和药物发现策略至关重要，需要进行详细的因果研究。三维模型的发展允许进行具有高度实验控制的此类研究，同时整合来自互补细胞培养模型和为此目的进行的研究的知识。结合使用人诱导多能干细胞，无论是否存在预先存在的遗传疾病，这些模型都将为在体外描绘机械生物学线索对人类心脏（病理）生理学的影响提供有希望的前景。
