(B-68) A Novel Heart-on-a-chip Model to Study Ischemic Injury

Introduction:: : Cardiovascular disease (CVD) remains the leading cause of death worldwide and the primary cause of CVD-related death is myocardial infarction (MI). Patients who experience a moderate-to-severe MI will eventually progress to heart failure where only transplantation is an effective treatment. The development of in-vitro models of MI could aid in the discovery and testing of novel therapeutics to treat MI; however, current 3D in-vitro models of MI do not display the range of injury present in-vivo (e.g. healthy, borderzone and infarct) and also lack in-line, non-invasive techniques for monitoring disease progression within the chip. Here, we demonstrate a heart-on-a-chip with a gradient of tissue health and sensors to monitor the functional effects of ischemic injury on cardiomyocytes (CMs).


Materials and Methods:: Our microfluidic chip was created via laser-cutting of gas-impermeable acrylic. Neonatal rat CMs were cultured in a GelMA hydrogel and a hypoxic gradient was created by altering medium flow to one of two channels on either side of the tissue. The heart-on-a-chip model was embedded with a multielectrode array to monitor the electrophysiological responses during hypoxia and reperfusion.


Results, Conclusions, and Discussions:: The development of a gradient of oxygen across the tissue was confirmed with HIF1a staining. Long-term culture of cardiac cells after reperfusion to assess tissue remodeling via label-free non-linear microscopy and functional changes via the bioelectronic interface is ongoing. The development of such a model holds great promise to replace animal studies with a highly-controlled platform to study disease progression and expedite preclinical studies on novel therapeutic strategies.


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