Quantifying the Compressive Force of 3D Cardiac Tissues via Calculating the Volumetric Deformation of Built‐In Elastic Gelatin Microspheres

Abstract Quantifying cardiac contractile force is of paramount important in studying mechanical heart failure and screening therapeutic drugs. However, most existing methods can only measure the in‐plane component of twitch force of cardiomyocytes, such that mismatching the centripetal compressive stress of heart beating in physiology. Here, a non‐destructive method is developed for quantifying the compressive stress and mapping the distribution of the local stress within the 3D cardiac tissues. In detail, elastic gelatin microspheres labeled with fluorescence beads are fabricated by microfluidic chips with high throughput, and they serve as built‐in pressure sensors which are wrapped by cardiomyocytes in 3D tissues. The deformation of microspheres and the displacements of fluorescent beads induced by the contraction of cardiomyocytes are demonstrated to characterize the amount and distribution of the centripetal compressive stress. Further, the method shows a potent capability to locally quantify contractile force variation of 3D cardiac tissues, which is induced by agonist (norepinephrine) and inhibitor (blebbistatin). On the whole, the method significantly improves the 3D measurement of mechanical force in vitro and provides a solution for locally quantifying the compressive stress within engineered cardiac tissues.