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用于模拟心脏微环境的生物反应器的设计与验证:一种结合周期性拉伸、电刺激和持续灌注的系统。

Design and validation of a bioreactor for simulating the cardiac niche: a system incorporating cyclic stretch, electrical stimulation, and constant perfusion.

机构信息

Department of Pharmacology and Toxicology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany.

出版信息

Tissue Eng Part A. 2013 Feb;19(3-4):403-14. doi: 10.1089/ten.TEA.2012.0135. Epub 2012 Dec 10.

Abstract

To simulate the cardiac niche, a bioreactor system was designed and constructed to incorporate cyclic stretch, rhythmic electrical stimulation, and constant perfusion. The homogeneity of surface strain distribution across the cell culture substrate was confirmed with ARAMIS deformation analysis. The proliferation marker, Ki-67, detected in human umbilical vein endothelial cells and 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide cytotoxicity assay performed on human atrial fibroblasts confirmed biocompatibility of this novel device. Cyclic stretch treatment for 24 h resulted in the perpendicular alignment of human atrial fibroblasts. An electrical stimulation system containing carbon electrodes was characterized by electrochemical impedance spectroscopy and charge injection/recovery studies, which indicated that increased corrosive reactions were associated with a higher input voltage and prolonged pulse duration. Field stimulation delivered through this system could induce rhythmic contractions in adult rat ventricular myocytes, with contractile characteristics similar to those paced in a standard field stimulation chamber. In conclusion, this bioreactor provides a novel tool to study the interaction between physical stimulation and cardiac cell physiology.

摘要

为了模拟心脏微环境,设计并构建了一个生物反应器系统,以实现周期性拉伸、节律性电刺激和持续灌注。通过 ARAMIS 变形分析证实了细胞培养基底表面应变分布的均一性。人脐静脉内皮细胞中的增殖标志物 Ki-67 和 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐细胞毒性测定证实了该新型装置的生物相容性。周期性拉伸处理 24 小时导致人心房成纤维细胞呈垂直排列。含有碳电极的电刺激系统通过电化学阻抗谱和电荷注入/恢复研究进行了表征,这表明增加的腐蚀性反应与更高的输入电压和更长的脉冲持续时间有关。通过该系统进行的场刺激可以诱导成年大鼠心室肌细胞产生有节奏的收缩,其收缩特性与在标准场刺激室中起搏的收缩特性相似。总之,该生物反应器为研究物理刺激与心脏细胞生理学之间的相互作用提供了一种新工具。

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