To reproduce hemodynamic stress microenvironments of endothelial cells in vitro is of vital significance, by which one could exploit the quantitative impact of hemodynamic stresses on endothelial function and seek innovative approaches to prevent circulatory system diseases. Although microfluidic technology has been regarded as an effective method to create physiological microenvironments, a microfluidic system to precisely reproduce physiological arterial hemodynamic stress microenvironments has not been reported yet. In this paper, a novel microfluidic chip consisting of a cell culture chamber with on-chip afterload components designed by the principle of input impedance to mimic the global hemodynamic behaviors is proposed. An external feedback control system is developed to accurately generate the input pressure waveform. A lumped parameter hemodynamic model (LPHM) is built to represent the input impedance to mimic the on-chip global hemodynamic behaviors. Sensitivity analysis of the model parameters is also elaborated. The performance of reproducing physiological blood pressure and wall shear stress is validated by both numerical characterization and flow experiment. Investigation of intracellular calcium ion dynamics in human umbilical vein endothelial cells is finally conducted to demonstrate the biological applicability of the proposed microfluidic system.

中文翻译：

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一种用于精确再现生理血压和内皮细胞壁剪切应力的微流体系统

体外重现内皮细胞的血流动力学应激微环境具有至关重要的意义，通过它可以利用血液动力学压力对内皮功能的定量影响，并寻求预防循环系统疾病的创新方法。尽管微流控技术已被认为是创造生理微环境的有效方法，但尚未报道能够精确再现生理动脉血流动力学应激微环境的微流控系统。在本文中，提出了一种新型微流控芯片，该芯片由带有片上后载组件的细胞培养室组成，该芯片通过输入阻抗原理设计来模拟全局血流动力学行为。开发了外部反馈控制系统以准确生成输入压力波形。建立了一个集总参数血液动力学模型 (LPHM) 来表示输入阻抗，以模拟片上全局血液动力学行为。还详细阐述了模型参数的敏感性分析。通过数值表征和流动实验验证了再现生理血压和壁剪切应力的性能。最后对人脐静脉内皮细胞中的细胞内钙离子动力学进行研究，以证明所提出的微流体系统的生物学适用性。