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开发微流控模型,以研究不同机械循环支持装置对脉动的内皮反应。

Development of microfluidic models to study endothelial responses to pulsatility with different mechanical circulatory support devices.

机构信息

School of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian 116024, Liaoning Province, P. R. China.

School of Mechanical Engineering, Dalian University of Technology, Dalian 116024, Liaoning Province, P. R. China.

出版信息

Analyst. 2024 Jun 24;149(13):3661-3672. doi: 10.1039/d4an00507d.

DOI:10.1039/d4an00507d
PMID:38819086
Abstract

Continuous-flow ventricular assist devices (CFVAD) and counterpulsation devices (CPD) are used to treat heart failure (HF). CFVAD can diminish pulsatility, but pulsatile modes have been implemented to increase vascular pulsatility. The effects of CFVAD in a pulsatile mode and CPD support on the function of endothelial cells (ECs) are yet to be investigated. In this study, two microfluidic models for culturing ECs are proposed to reproduce blood pressure (BP) and wall shear stress (WSS) on the arterial endothelium while using these medical devices. The layout and parameters of the two microfluidic systems were optimized based on the principle of hemodynamic similarity to efficiently simulate physiological conditions. Moreover, the unique design of the double-pump and double afterload systems could successfully reproduce the working mode of CPDs in an microfluidic system. The performance of the two systems was verified by numerical simulations and experiments. BP and WSS under HF, CFVAD in pulsatile modes, and CPD were reproduced accurately in the systems, and these induced signals improved the expression of Ca, NO, and reactive oxygen species in ECs, proving that CPD may be effective in normalizing endothelial function and replacing CFVAD to a certain extent to treat non-severe HF. This method offers an important tool for the study of cell mechanobiology and a key experimental basis for exploring the potential value of mechanical circulatory support devices in reducing adverse events and improving outcomes in the treatment of HF in the future.

摘要

连续流心室辅助装置 (CFVAD) 和反搏装置 (CPD) 用于治疗心力衰竭 (HF)。CFVAD 可以降低脉动性,但已经实施了脉动模式以增加血管脉动性。CFVAD 在脉动模式下和 CPD 支持对内皮细胞 (EC) 功能的影响尚未得到研究。在这项研究中,提出了两种用于培养 EC 的微流控模型,以在使用这些医疗设备的同时再现动脉内皮上的血压 (BP) 和壁切应力 (WSS)。两种微流控系统的布局和参数基于血液动力学相似性原理进行了优化,以有效地模拟生理条件。此外,双泵和双后负荷系统的独特设计可以成功地在微流控系统中再现 CPD 的工作模式。通过数值模拟和实验验证了两个系统的性能。在系统中准确再现了 HF 下的 BP 和 WSS、CFVAD 的脉动模式和 CPD,这些诱导信号提高了 EC 中 Ca、NO 和活性氧的表达,证明 CPD 可能有效规范内皮功能,并在一定程度上替代 CFVAD 来治疗非严重 HF。该方法为细胞机械生物学研究提供了重要工具,并为探索机械循环支持装置在减少 HF 治疗中不良事件和改善结果方面的潜在价值提供了关键的实验基础。

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