Biohybrid Thin Film Models of Cardiac Output

Microphysiological systems (MPS) have recently emerged as a powerful set of tools for modeling cardiac diseases <i>in vitro</i>. Composed of both synthetic and cellular material components, these devices use tissue engineering to mimic the native microenvironment of the heart, thus allowing researchers to recapitulate both healthy and disease cellular phenotypes. This includes systems such as muscular thin films (MTFs) cantilevers, which have previously been used to model features such as cellular contractility and calcium propagation. MPS represent an important steppingstone in improving therapeutic testing, as they can help provide mechanistic insights into disease modeling, while providing reproducible metrics of cardiac performance. The hope is that by building more realistic <i>in vitro</i> models, these types of systems can help bridge the gap between laboratory and clinical testing, leading to improved clinical outcomes. However, traditionally it has been difficult to obtain similar metrics from both <i>in vitro</i> and <i>in vivo </i>studies, especially in a high throughput manner. For the heart, this includes cardiac output, which serves as a key clinical metric for assessing the health of the heart. To address this challenge, here we demonstrate how existing MTF platforms can be adapted to serve as a simplified model of the left ventricle’s native myocardium, <i>In vivo</i>, the left ventricle’s myofibril architecture is organized in helically, creating a twist-based mechanism to efficiently pump blood to the remainder of the body. To model this process, here we formed an angled tissue engineered cantilever model which could efficiently pump the surrounding fluid media. Envisioning that these thin films represent a transmural section of ventricular endocardium, we then measured the net flux of media occurring transverse to the longitudinal axis of the cantilever. By measuring the resulting fluid flows using particle imaging velocimetry (PIV), we then quantified how much thrust these biohybrid systems were capable of generating, using this as a basic analog to cardiac output. As the resulting cardiac outputs were angle dependent, we then used both computational simulation, and experimental testing to determine which angles produced the maximal output. Overall, by incorporating fluid-dynamics with a previously known high throughput screening model (<i>e.g</i>. MTFs), this study can help bridge the gap between clinical and <i>in vitro</i> measurements. while suggesting that angled tissue engineered thin films may serve as a simplified platform for studying key features of cardiac health and disease in the laboratory.