A Microfabricated Platform to Measure and Manipulate the Mechanics of Engineered Cardiac Microtissues

Cardiac tissue engineering is currently limited by the incapacity to test the wide range of parameters that might impact the engineered tissue in a high throughput and combinatorial manner. Here we used microelectromechanical systems (MEMS) technology to generate arrays of cardiac microtissues (CMTs) embedded within three-dimensional micropatterned matrices. Microcantilevers constrain CMT contraction and report generated forces. We demonstrate the ability to routinely produce ∼200 CMTs per million cardiac cells whose spontaneous contraction frequency, duration, and forces can be tracked. Independently varying the mechanical stiffness of the cantilevers and collagen matrix revealed that the CMT contractility increased with boundary or matrix rigidity. We also show that the combination of electrical stimulation and auxotonic load strongly improve both the structure and the function of the CMTs. Finally, we demonstrate the suitability of our technique for high throughput monitoring of drug-induced changes in spontaneous frequency or contractility in CMTs.