PROJECT SUMMARY Approximately every 40 seconds, someone will suffer a myocardial infarction (MI) in the US. While mortality due to acute MI has decreased over the past two decades, long-term consequences and comorbidities associated with chronic MI are increasing. In many cases, post-MI left ventricular (LV) remodeling manifests as progressive changes in LV structure and function. This remodeling initiates a degenerative cycle in which altered myocardial wall mechanics around the infarcted region cause the heart to mechanically compensate, resultantly placing still more strain on the infarct. Consequently, LV remodeling is the cause of approximately 70% of all heart failure (HF) cases, which kill approximately 100,000 Americans each year. Current treatments for chronic MI, HF, and LV remodeling include pharmacological treatments such as ACE-inhibitors and β- blockers, external mechanical ventricular assist devices (VADs), or invasive coronary revascularization procedures. These interventions are highly invasive and/or stopgap remedies, requiring continuous local modulation of the myocardial mechanics at the infarct. This proposal leverages auxetic materials, which counterintuitively get thicker rather than thin when stretched, to provide a means of restoring pumping function to the infarcted region of the heart. By fixing an auxetic ventricular support device (auxVSD) to the expanding, infarcted tissue, I plan to harness the energy currently wasted in the nonbeating infarct to instead stretch and expand an auxVSD, which would in turn stiffen and press against the myocardium, contributing to the ejection of blood during systole. Aim 1 will focus on the design, fabrication, and testing of potential auxetic structures and materials. Mechanical simulations will be used to identify auxetic structures that possess a favorable combination of displacement and force due to the auxetic effect. Concurrently, physical models will be fabricated for in vitro mechanical testing to inform the real-world feasibility of the simulations as well as provide preliminary information regarding the expected performance of an auxVSD in an in vivo animal model. In Aim 2 the efficacy of an auxVSD will be tested in an animal model of chronic MI and LV expansion to demonstrate its improvement of cardiac function through the dynamic modulation of myocardial mechanics in the infarcted region. Overall, this project design is both translational and highly-cross disciplinary in nature. Furthermore, improved understanding of the tissue- and organ-level changes associated with the onset and progression of MI will guide and validate this research through advanced cardiac imaging. These studies will not only provide a platform for rigorous multi-disciplinary integrated training in biomedical device design, mechanisms of cardiac disease, computational modeling, and translational imaging, but will also catapult a career that is focused on developing novel, technology-driven therapeutic ...