Abstract 713: Engineering Complex Tissue Mechanical Environment for Cardiac Microtissues Derived From Human Induced Pluripotent Stem Cells

Abstract

Previous studies of hiPSC-based cardiac tissue models mainly focused on uniform tissue mechanical environment, which is not sufficient to recapitulate the complex and heterogeneous tissue mechanical environment that would lead to cardiac contractile dysfunction. To create a 3D cardiac tissue model with nonuniform mechanical environment, we have developed state-of-art laser-based 3D bioprinting technology to fabricate “mechanical hybrid” scaffolds comprised of layers of parallel aligned high-aspect-ratio (100:1) fibers.We fabricated the double-hybrid (DH) scaffolds with “1:1 thin-thick” design by positioning the thin fibers (5 μm, low stiffness) next to the thick fiber (10 μm, high stiffness) to create a mismatch region in the center ( Fig. A ). The entire microtissue had to self-balance the force generation between high and low stiffness for synchronized contraction ( Fig. B ). This resulted in tissue hypertrophy at the high stiffness side with larger tissue cross-section comparing to low stiffness side ( Fig. C ). We also determined the local contractile velocities from each segment of the microtissues at different spatial locations, which showed a trend of exponential decay on the contractile velocities from edge to center ( Fig. D ). The difference in the decay rate between thick side of the DH scaffolds (DH-K) and thin side of the DH scaffolds (DH-N) indicated the contractile imbalance on the two sides of the entire microtissues. We also calculated the force output of the cardiac microtissues on DH-K side, which showed a HCM-like diastolic dysfunction comparing to the force output from single scaffolds with thick fibers ( Fig. E ).