Heart-On-A-Chip Platform For Assessing Toxicity Of Air Pollution Related Nanoparticles

Accumulating evidence indicates that air pollution contributes to serious and fatal damage to the cardiovascular system, yet the mechanisms that drive air pollution associated cardiovascular disease and dysfunction remain unclear. In an effort to create a more predictive in vitro model, a 3D platform, known as integrated vasculature for assessing dynamic events is used, that supports the combination of dense human induced pluripotent stem cell derived cardiac tissue and vascular interface, to unravel the impact of nanoscale air pollution on endothelial cells and cardiac tissue. Air pollution relevant nanoparticles (CuO, SiO2) and a control (Au) are used to predict the toxic effects on the cardiovascular system under perfusion. It is demonstrated that CuO nanoparticles are highly toxic, as they are able to translocate into the cardiac tissue and induce electrical and contractile dysfunction through generation of reactive oxygen species and subsequently lead to disruption of cardiac troponin T and secretion of biomarkers associated with cardiac injury (B-type natriuretic peptide, N-terminated pro-hormone BNP, and Troponin I). SiO2, on the other hand, causes the secretion of pro-inflammatory cytokines, and modulates the intracellular Ca2+ handling. This microengineering approach may offer new opportunities to more accurately model cardiovascular responses to nm-sized air pollution.