Programming Complex Cellular Alignment in Engineered Cardiac Tissue

Toward more physiological disease models and efficacious therapies for heart failure, researchers aim to recreate the three-dimensional myocardial architecture in engineered tissues using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Here, we report a novel bioprinting method to align heart tissue in arbitrary geometries at high cellular densities. First, we generated a bioink composed of cellularly aligned, contractile cardiac tissues, which we termed anisotropic organ building blocks (aOBBs). Next, the extrusion of this densely compacted bioink caused the aOBBs to orient parallel to the direction of the print path. To demonstrate our spatial control of cardiomyocyte alignment, we generated linear, spiral, and chevron patterned centimeter-scale sheets. In filaments suspended between elastomeric pillars, discrete aOBBs fused into electromechanically synchronous tissue. Cardiac maturation markers and functional values of force and conduction velocity increased overtime. These studies demonstrated the capacity to generate functional heart tissue with arbitrarily complex cellularly alignment at high cellular densities.