People are continuously exposed to a variety of potentially toxic chemicals present in the environment, while unintentional combinations with drugs may result in synergistic effects. In this context, there is a growing demand for standardised devices and protocols to assess the toxicity of compounds and their mixtures to support robust procedures for risk assessment. On the other hand, 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 components of in vitro platforms for cardiotoxicity testing.

The ALTERNATIVE project aims at developing an innovative in vitro platform to detect the cardiotoxicity of chemicals and their mixtures. In detail, a three-dimensional (3D) bioengineered human myocardial tissue has been developed and cultured in an integrated and sensorised microfluidic bioreactor system.

The myocardial tissue model was designed in the form of a biphasic scaffold based on a 3D-printed construct and a photo-responsive Gelatin-Methacryloyl (GelMA) hydrogel, working as a structural/mechanical framework and cell carrier for cell homing, respectively. The construct's forming material was a custom-made poly(ester urethane) (PUR) showing elastomeric-like properties. The PUR 3D structure was microfabricated by melt-extrusion additive manufacturing and functionalised with fibronectin through plasma treatment. Conversely, the GelMA hydrogel (5%w/v) was loaded with human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) and human coronary artery endothelial cells (HCAECs) (80:20 ratio) and then used to infiltrate the 3D matrices. Cells showed good viability in the construct and a significant modulation of cardiac genes associated with cardiac structure, cell interactions, metabolism and maturation.

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.