Engineered Microtissues for Real-Time Characterization of Cardiomyocyte Function

Abstract

Engineered cardiac tissue models become increasingly important for understanding normal and disease cardiac physiology [1]. Where clinical diagnostic tools usually measure overall function of the heart, cardiac tissue models make it possible to focus on single CMs and their microenvironment. The use of in-vitro cardiac disease models can give more insight in the functionality changes of CMs during disease and thereby speed up the development of new therapies. Therefore, we aim to develop a model for healthy and diseased myocardium to study the effect of diseased microenvironments on the mechanical performance of CMs. The platform consists of 3D engineered microtissues with matrix, CMs and fibroblasts (FBs) on an array of polydimethylsiloxane (PDMS) microposts and allows for real-time characterization of CMs and their surrounding matrix. The design was adapted from Legant et. al. [2] and enables us to measure inhomogeneous tissue forces which may occur if not all cells contract equally. Here we focus on optimization and validation of the platform to measure contraction forces and gain insight in CM mechanical functioning.