I-Wire Heart-on-a-Chip II: Biomechanical analysis of contractile, three-dimensional cardiomyocyte tissue constructs.
I-Wire Heart-on-a-Chip II: Biomechanical analysis of contractile, three-dimensional cardiomyocyte tissue constructs.
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DOI：
10.1016/j.actbio.2016.11.010
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发表时间：
2017-01-15
影响因子：
9.7
通讯作者：
Merryman WD
中科院分区：
文献类型：
--
作者：
Schroer AK;Shotwell MS;Sidorov VY;Wikswo JP;Merryman WD
该伴随研究采用改良的Hill肌肉力学模型对“I-Wire”平台进行生物力学分析，该模型允许进一步表征结构功能和对扰动的反应。I-Wire工程化心脏组织构建体（ECTC）是一种研究生长性收缩期间心脏细胞力学的新型实验平台。虽然被动生物材料通常表现出非线性和耗散行为，但活性组织等效物（如ECTC）也消耗代谢能量来执行机械功，这在量化其特性方面提出了额外的挑战。I-Wire模型在治疗前、治疗期间和治疗后使用对增加施加张力的被动机械响应来测量结构的固有应力和抗拉伸性。blebbistatin和异丙肾上腺素都降低了预应力和结构刚度;然而，blebbistatin治疗消除了随后的力产生潜力，而异丙肾上腺素增强了这一特性。我们证明，所描述的模型可以复制这些结构的内在变化的力产生潜力的反应，增加频率的刺激和减少起始长度。该分析提供了I-Wire平台的有用数学模型，增加了可从器械中获得的参数数量，并可作为非线性活性生物材料定量表征的证明。我们预计，I-Wire结构的这种定量分析将证明在用于心脏再生医学之前对鉴定患者特异性心肌细胞和成纤维细胞有用。
This companion study presents the biomechanical analysis of the “I-Wire” platform using a modified Hill model of muscle mechanics that allows for further characterization of construct function and response to perturbation. The I-Wire engineered cardiac tissue construct (ECTC) is a novel experimental platform to investigate cardiac cell mechanics during auxotonic contraction. Whereas passive biomaterials often exhibit nonlinear and dissipative behavior, active tissue equivalents, such as ECTCs, also expend metabolic energy to perform mechanical work that presents additional challenges in quantifying their properties. The I-Wire model uses the passive mechanical response to increasing applied tension to measure the inherent stress and resistance to stretch of the construct before, during, and after treatments. Both blebbistatin and isoproterenol reduced prestress and construct stiffness; however, blebbistatin treatment abolished subsequent force-generating potential while isoproterenol enhanced this property. We demonstrate that the described model can replicate the response of these constructs to intrinsic changes in force-generating potential in response to both increasing frequency of stimulation and decreasing starting length. This analysis provides a useful mathematical model of the I-Wire platform, increases the number of parameters that can be derived from the device, and serves as a demonstration of quantitative characterization of nonlinear, active biomaterials. We anticipate that this quantitative analysis of I-Wire constructs will prove useful for qualifying patient-specific cardiomyocytes and fibroblasts prior to their utilization for cardiac regenerative medicine.