UC Irvine

The heart is a complex organ whose structure and function are intricately linked at multiple length scales. Though several advancements have been achieved in the field of cardiac tissue engineering, current in vitro cardiac tissues do not fully replicate the structure or function necessary for effective cardiac therapy and cardiotoxicity studies. This is partially due to a deficiency in current understandings of cardiac tissue organization’s potential downstream effects, such as changes in gene expression levels. We developed a novel in vitro tool that can be used to decouple and quantify the contribution of organization and associated downstream effects to tissue function. To do so, cardiac tissues were designed to be organized anisotropically on a local scale and with any desired organization on a global scale. This study’s results showed that if the downstream effects were muted, the relationship between developed force and tissue organization was a surprisingly simple sum of force pseudovectors. Thus, a quantitative tool was developed to predict the generated stress based on organization. Furthermore, it was demonstrated that the tool could be used to estimate the changes in stress production due to downstream effects decoupled from tissue architecture. This has the potential to elucidate properties coupled to tissue architecture, which change force production and pumping function in the diseased heart or stem-cell derived tissues.