Cardiac fibrosis is a disease state characterized by excessive collagenous matrix accumulation within the myocardium that can lead to ventricular dilation and systolic failure. Current treatment options are severely lacking due in part to the poor understanding of the complexity of molecular pathways involved in cardiac fibrosis. To close this gap, in vitro model systems that recapitulate the defining features of the fibrotic cellular environment are in need. Type I collagen, a major cardiac extracellular matrix protein and the defining component of fibrotic depositions, is an attractive choice for a fibrosis model, but demonstrates poor mechanical strength due to solubility limits. However, plastic compression of collagen matrices is shown to significantly increase its mechanical properties. Here, confined compression of oligomeric, type I collagen matrices is utilized to resemble defining hallmarks seen in fibrotic tissue such as increased collagen content, fibril thickness, and bulk compressive modulus. Cardiomyocytes seeded on compressed matrices show a strong beating abrogation as observed in cardiac fibrosis. Gene expression analysis of selected fibrosis markers indicates fibrotic activation and cardiomyocyte maturation with regard to the existing literature. With these results, a promising first step toward a facile heart‐on‐chip model is presented to study cardiac fibrosis.

中文翻译：

---

I型胶原基质的致密化作为心脏纤维化的模型

心脏纤维化是一种疾病状态，其特征在于心肌内过多的胶原蛋白基质蓄积，可导致心室扩张和收缩衰竭。由于缺乏对涉及心脏纤维化的分子途径的复杂性的了解，目前严重缺乏当前的治疗选择。为了弥合这一差距，需要体外模型系统来概括纤维化细胞环境的定义特征。I型胶原蛋白是心脏主要的细胞外基质蛋白，是纤维化沉积的重要组成部分，是纤维化模型的诱人选择，但由于溶解度限制，其机械强度很低。然而，胶原蛋白基质的塑性压缩显示出显着增加其机械性能。在这里，低聚体的压缩，I型胶原蛋白基质被用来类似于在纤维化组织中看到的标志性特征，例如增加的胶原蛋白含量，原纤维厚度和体积压缩模量。如在心脏纤维化中所观察到的，接种在压缩基质上的心肌细胞显示出强烈的搏动性消除。相对于现有文献，所选纤维化标记物的基因表达分析表明纤维化激活和心肌细胞成熟。有了这些结果，提出了一个有希望的，迈向简便的心脏芯片模型的第一步，以研究心脏纤维化。相对于现有文献，所选纤维化标记物的基因表达分析表明纤维化激活和心肌细胞成熟。有了这些结果，提出了一个有希望的，迈向简便的心脏芯片模型的第一步，以研究心脏纤维化。相对于现有文献，所选纤维化标记物的基因表达分析表明纤维化激活和心肌细胞成熟。有了这些结果，提出了一个有希望的，迈向简便的心脏芯片模型的第一步，以研究心脏纤维化。