Cardiac tissue engineering has a potential to provide functional, synchronously contractile tissue constructs for heart repair, and for studies of development and disease using in vivo–like yet controllable in vitro settings. In both cases, the utilization of bioreactors capable of providing biomimetic culture environments is instrumental for supporting cell differentiation and functional assembly. In the present study, neonatal rat heart cells were cultured on highly porous collagen scaffolds in bioreactors with electrical field stimulation. A hallmark of excitable tissues such as myocardium is the ability to propagate electrical impulses. We utilized the method of optical mapping to measure the electrical impulse propagation. The average conduction velocity recorded for the stimulated constructs (14.4 ± 4.1 cm/s) was significantly higher than that of the nonstimulated constructs (8.6 ± 2.3 cm/s, p = 0.003). The measured electrical propagation properties correlated to the contractile behavior and the compositions of tissue constructs. Electrical stimulation during culture significantly improved amplitude of contractions, tissue morphology, and connexin-43 expression compared to the nonsimulated controls. These data provide evidence that electrical stimulation during bioreactor cultivation can improve electrical signal propagation in engineered cardiac constructs.
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机译:心脏组织工程学有潜力提供功能性,可同步收缩的组织构造物,以进行心脏修复,以及使用体内样但可控的体外设置研究发育和疾病。在这两种情况下,利用能够提供仿生培养环境的生物反应器有助于支持细胞分化和功能组装。在本研究中,新生大鼠心脏细胞在具有电场刺激的生物反应器中的高度多孔胶原支架上培养。诸如心肌等可兴奋组织的标志是具有传播电脉冲的能力。我们利用光学映射的方法来测量电脉冲传播。刺激的构造物记录的平均传导速度(14.4±4.1 cm / s)明显高于未刺激的构造物的平均传导速度(8.6±2.3 cm / s,p = 0.003)。测得的电传播特性与组织结构的收缩行为和组成相关。与非模拟对照组相比,培养期间的电刺激显着改善了收缩幅度,组织形态和连接蛋白43表达。这些数据提供了证据,表明生物反应器培养过程中的电刺激可以改善工程心脏结构中的电信号传播。
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