Biomaterials for Cardiac Regeneration

About This Grant

1 PROJECT SUMMARY (30 lines) 2 3 The objective of this proposal is to investigate the ability of an injectable polypeptide scaffold to 4 improve patient outcomes after myocardial infarction. This is motivated by the evidence that 5 cardiovascular disease is the leading cause of death in the world, with an estimated $127 billion 6 in healthcare costs annually in the United States. The pathologic remodeling induced by 7 cardiovascular disease, and specifically myocardial ischemia, can progress to heart failure in 1 in 8 3 patients, which may lead to devastating functional disability. The gold standard treatment for 9 myocardial ischemia is coronary artery bypass grafting (CABG) and percutaneous coronary 10 intervention (PCI). These modalities function by restoring blood flow to ischemic areas as 11 promptly as possible to limit the extent of the damage. However, they do nothing to address the 12 pathologic remodeling process that has already started to unfold with the initial insult. While PCI 13 and CABG are important to offset further functional decline, innovative treatment modalities are 14 needed to inhibit and reverse pathologic remodeling once it has already begun. Motivated by this 15 clear clinical need, we will investigate the applicability of partially ordered polypeptides (POPs) to 16 improve outcomes after myocardial infarction. POPs are a unique biomaterial that transition from 17 an injectable liquid at room temperature to a physically crosslinked, porous network at body 18 temperature. POPs are highly biocompatible, integrate into surrounding tissue, and initiate 19 remodeling, cell infiltration, and neovascularization. Further, their ability to phase transition at 20 body temperature allows for easy handling and integration in the operating room, as well as a 21 scalable manufacturing process that has the capability to be a clinically translatable product. Our 22 central goal will be to demonstrate that POPs are uniquely suited to provide the needed 23 mechanical support and well vascularized microenvironment essential for successful repair and 24 reversal of pathologic remodeling in cardiomyocytes. Our strategy will include tailoring POPs to 25 the correct porous microarchitecture and mechanical properties for their application in the heart. 26 We will then investigate the ability of POPs to augment outcomes following myocardial ischemia 27 in murine models of myocardial infarction. Functional and histological testing will be performed 28 and compared to controls. If this proposal is successful, it will provide an essential foundation to 29 commence large animal testing and translation into clinical settings. Therefore, the application of 30 POPs to this disease process has the potential to have a transformative impact on the lives of 31 patients who have undergone myocardial infarction by preserving cardiac function, and thus 32 reducing long term morbidity and mortality.