3D printed PU/GelMA biphasic scaffold for detecting the cardiotoxicity of chemicals.

Humans are exposed to potentially toxic chemicals present in the environment and unintentional combinations with drugs may result in synergistic effects. Cardiotoxicity is not a separate endpoint in current toxicology studies, although several chemicals have shown cardiotoxic properties. In view of these observations, 3D bioengineered cardiac tissue models are promising elements of in vitro platforms for cardiotoxicity testing. Here we present a myocardial tissue model, designed in the form of a biphasic scaffold based on a 3D-printed construct and a photo-responsive hydrogel, working as structural/mechanical framework and cell carrier for cell homing, respectively. The construct's forming material is a custom-made poly(ester urethane) (PU) which demonstrated elastomeric-like properties. The PU was microfabricated into a 3D structure by melt-extrusion additive manufacturing, and the construct was functionalised with an ECM protein (fibronectin) by plasma treatment. The hydrogel was obtained by irradiating GelMA solutions under cell-friendly conditions. Different GelMA concentrations were exploited to tune the mechanical properties of gels and simulate the aging process of the native tissues. The gel was seeded with human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) and human coronary artery endothelial cells (HCAECs). Cells showed viability, contraction ability and modulation of cardiac genes (CX43, ACTN2, and BNP).