(175ba) From Cell Pairs to Tissue Chips: Multi-Scale In Vitro Models for Screening Engineered Nanomaterial Toxicity

While engineered nanomaterials (ENMs) have emerged as important components of various commercial products, human exposure to ENMs has been associated with negative health outcomes such as cardiovascular diseases. To better understand and quantify the pathophysiological effects of ENM exposure, there is a pressing need to develop in vitro models that faithfully recapitulate the native form and function of cells and tissues. In particular, two platforms developed for screening ENM effects in the cardiovascular space will be presented: 1) geometrically-controlled cell pairs as a reductionist model of the endothelial barrier; and 2) fiber-based cardiac microphysiological devices for contractile stress measurements. These models allow for a multi-scale assessment of the effects of nano-bio interactions at different stages of ENM biodistribution—from the translocation of ENMs across barrier tissues such as the endothelium, to their delivery towards target tissues such as the myocardium. Endothelial cell pairs produced via protein micropatterning allow for a quantitative assessment of ENM-induced changes in multiple cellular-level parameters relevant to vascular barrier integrity, such as cellular morphology, junction protein expression, intercellular gap formation and cytoskeletal network organization. On the other hand, our “chip-based” platform can be used for measuring changes in tissue-level cardiac function, such as contractile stress and beat rate, during ENM exposure. Aligned polydopamine (PDA)/polycaprolactone (PCL) nanofibers were used as a tissue scaffold for this device in order to mimic the 3D architecture of cardiac microenvironments under physiological conditions. An instrumented version of this platform with embedded strain sensors will also be presented, which provides a way to continuously and non-invasively monitor the effects of ENM on cardiac tissue contractility at different time points. Collectively, the in vitro platforms presented herein provide physiologically relevant models of ENM exposure routes towards a more comprehensive evaluation of microvascular and cardiac response profiles to different nanomaterials.