IMPROVING WOUND HEALING THROUGH THE USE OF TETRAZINE-MODIFIED ALGINATE
Esmarline J. De Leon-Peralta1, Brian Kwee2, Yevgeny Brudno2, David Mooney2.
1University of Puerto Rico, Mayaguez Campus, Mayaguez, PR, 2Harvard University, Cambridge, MA.
Ischemic diseases, such as myocardial infarction and peripheral arterial disease, are a leading cause of death globally. There has been increasing interest in treating these diseases with factors that induce angiogenesis: the growth of new blood vessels from pre-existing blood vessels. We have recently shown that alginate linked to tetrazine helps induce a greater recovery in blood perfusion compared to unmodified alginate in a murine model of hindlimb ischemia. The objective of this project is to understand how this biomaterial induces recovery in blood perfusion. Our hypothesis is that tetrazine acts directly on endothelial cells to induce angiogenesis and also activates immune cells that are pro-angiogenic. To validate our hypothesis, we have performed in vitro angiogenesis assays to study if tetrazine-modified alginate induces endothelial cell sprouting. Additionally, we have performed histology and immunohistochemistry on ischemic muscles from our in vivo experiments to see if this biomaterial increases blood vessel density, blood vessel remodeling, and the presence of pro-angiogenic immune cells. Our findings may lead to a novel method for treating people with ischemic diseases.