Heart-on-a-chip

Abstract Heart diseases, such as myocardial infarction, hypertrophy, and atherosclerosis, are the highest worldwide death cause, being an important focus for new treatments development. Furthermore, half of the drugs retracted from the market in the last 30 years induced heart electrophysiological disfunctions and muscular damage resulting from their side effects. This highlights the limitations of currently used drug testing methods to evaluate the effect of compounds on the heart functionality. Myocardium therapies and cardiotoxicity are currently studied using two-dimensional (2D) static cultures of cardiomyocytes or, alternatively, animal models. 2D cell cultures are oversimplified and fail to reproduce cell orientation as well as cardiac tissue physiology, whereas animal models have demonstrated to be not enough efficient in predicting human responses. Cardiovascular in vitro models are highly desirable due to their relative lower costs, due to their potential to better mimic human physiology by using human cells and due to the societal concerns on animal testing. However, the complex dynamics are a strong limiting factor when aiming to capture the heart main physiological functions in an in vitro model. The conventional 2D cardiovascular in vitro models cannot replicate physiological conditions, which are conditioned by physical stimulations, such as electrical signaling, mechanic strain, or shear stress, that are important factors in setting the alignment, structure, and phenotype of cardiac cells. Microfluidics, and by extension organ-on-chip devices, are highly versatile and potentially suitable to provide continuous media perfusion to cells, allowing to control shear stresses, and to architect specific spatial distributions of different cell types. Furthermore, they can be also easily integrated with other technologies to provide cells with stimulus of different natures such as mechanical or electrical ones.