Generation of functional cardiac microtissues in a beating heart-on-a-chip.

With the increasing attention on cardiovascular disorders and the current inability of pre-clinical models to accurately predict human physiology, the need for advanced and reliable heart in vitro models is paramount. Microfabrication technologies provide potential solutions in the organs-on-chip systems: microengineered devices where cell cultures can be hosted and cultured to develop three-dimensional models or microtissues with high similarity to human physiology. We here described the fabrication and operation procedures for a beating heart-on-a-chip. The device features a culture region for a 3D cardiac microtissue and a system for applying tuned mechanical stimulation during culture to improve cardiac development. We additionally describe procedures for characterizing tissue maturation via immunofluorescence and functional evaluations of microtissue contractility.