Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
Cellular, Molecular and Developmental Biology Program, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
J Tissue Eng Regen Med. 2017 Feb;11(2):342-353. doi: 10.1002/term.1915. Epub 2014 Jun 11.
Mechanical stimulation has been used extensively to improve the function of cardiac engineered tissue, as it mimics the physical environment in which the tissue is situated during normal development. However, previous mechanical stimulation has been carried out under a constant frequency that more closely resembles a diseased heart. The goal of this study was to create a bioreactor system that would allow us to control the mechanical stimulation of engineered cardiac tissue on a cycle-by-cycle basis. This unique system allows us to determine the effects on cardiac construct function of introducing variability to the mechanical stretch. To test our bioreactor system, constructs created from neonatal rat cardiomyocytes entrapped in fibrin hydrogels were stimulated under various regimes for 2 weeks and then assessed for functional outcomes. No differences were observed in the final cell number in each condition, indicating that variability in frequency did not have a negative effect on viability. The forces were higher for all mechanical stimulation groups compared to static controls, although no differences were observed between the mechanically stimulated conditions, indicating that variable frequency on a cycle-by-cycle basis has limited effects on the resulting force. Although differences in the observed twitch force were not observed, differences in the protein expression indicate that variable-frequency mechanical stimulation had an effect on cell-cell coupling and growth pathway activation in the constructs. Thus, this bioreactor system provides a valuable tool for further development and optimization of engineered myocardial tissue as a repair or replacement strategy for patients undergoing heart failure. Copyright © 2014 John Wiley & Sons, Ltd.
机械刺激已被广泛用于改善心脏工程组织的功能，因为它模拟了组织在正常发育过程中所处的物理环境。然而，以前的机械刺激是在一个更接近患病心脏的恒定频率下进行的。本研究的目的是创建一个生物反应器系统，使我们能够在逐个周期的基础上控制对工程心脏组织的机械刺激。这个独特的系统使我们能够确定向机械拉伸引入可变性对心脏构建体功能的影响。为了测试我们的生物反应器系统，将包埋在纤维蛋白水凝胶中的新生大鼠心肌细胞制成的构建体在各种方案下刺激 2 周，然后评估其功能结果。在每种条件下，最终细胞数量没有差异，表明频率的可变性对活力没有负面影响。与静态对照相比，所有机械刺激组的力都更高，尽管在机械刺激条件之间没有观察到差异，表明逐个周期的频率变化对产生的力的影响有限。尽管观察到的抽搐力没有差异，但蛋白质表达的差异表明，可变频率的机械刺激对构建体中的细胞-细胞偶联和生长途径激活有影响。因此，该生物反应器系统为进一步开发和优化作为心力衰竭患者修复或替代策略的工程心肌组织提供了有价值的工具。版权所有©2014 年 John Wiley & Sons, Ltd.
