3D printing of structural bionic and functionalized hydrogels for the construction of macroscale human cardiac tissues.

Abstract

Capturing the intricate structural, mechanical, and electrophysiological properties of the native heart in models is crucial for achieving efficient physiological pumping function; however, current approaches have shown limited success in replicating these features essential for producing tissue models on complex geometries that accurately mimic full cardiac function. Here, we present a novel hydrogel ink formulation combining a conductive, biocompatible ionic liquid with a photosensitive poly(vinyl alcohol)-based hydrogel, enabling 3D printing of biomechanically compatible heart valves and 3D tissue engineering scaffolds. These scaffolds mimic the helical and circumferential alignments characteristic of the ventricular and atrial muscle layers, respectively, and incorporate a hollow auxetic structure to achieve mechanical anisotropy. The precision of the printed double-sided grooved patterns provides microscale geometric cues, facilitating the self-organization and maturation of human cardiomyocytes into anisotropic muscular tissues in vitro. This approach enables the biofabrication of tissue-engineered ventricles and atria, with helically and circumferentially aligned models exhibiting biomimetic twisting, rolling dynamics, and electrophysiological properties. The resulting 3D-printed multichambered heart models-including both four-chambered and two-chambered configurations with integrated cardiac chambers, vessels, and valves-demonstrate anisotropic electrophysiological and contractile behaviors. This work establishes a scalable platform for engineering electromechanically coupled cardiac tissues, advancing in vitro organ modeling and providing a foundation for future regenerative applications.