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 carrier for cell homing, respectively.

The construct's forming material was a custom-made poly(ester urethane) (PU) with elastomeric-like mechanical properties. The PU was microfabricated into a 3D structure by melt-extrusion additive manufacturing, and the construct was functionalised with an extracellular matrix protein (fibronectin) by plasma treatment.

The hydrogel was obtained by irradiating methacryloyl gelatin (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 cardiac tissue. 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).

ACKNOWLEDGEMENTS: This work was supported by the European Union’s Horizon 2020 research and innovation program (grant# 101037090). The content of this abstract reflects only the author’s view, and the Commission is not responsible for any use that may be made of the information it contains.