Bioengineered Human Cardiac Ventricular Model with Transmural Helical Remodeling

The heart's helical myocardial architecture enables efficient contraction by generating a twisting motion to eject blood. However, few existing approaches can replicate the complex structure-function relationships that govern cardiac performance at the macroscopic organ level. Here, we present a human 3D ventricular model with helical transmural architecture, engineered using multilayered, patterned cardiac sheets assembled on a 3D-printed conical mold. Tissue-engineered ventricles with cardiomyocytes pre-aligned parallel or perpendicular to the long axis exhibited enhanced contractile pressures and maximum capture rates compared to tissue constructs with angled or randomly oriented cells. Notably, the inner layers of perpendicular sheets underwent spontaneous realignment over 4 days, adopting a parallel orientation and forming a physiologically relevant helical transmural structure, whereas minimal remodeling was observed in parallel or angled sheets. Finite element analysis of engineered ventricles revealed that circumferential alignment induces the highest perpendicular shear stress at the inner layer, while longitudinal alignment generates the highest parallel stress, suggesting that cells remodel to reduce local shear stress. By enabling dynamic remodeling of organized cardiac sheets within a physiologically relevant 3D geometry, our platform demonstrates how mechanical cues guide transmural reorientation and tissue remodeling, and elucidates the mechanobiology underlying myocardial structure-function relationships.