Biodegradable Elastomers and Resorbable Synthetic Vascular Grafts

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Project Summary Occlusive artery diseases are a leading cause of death worldwide. Only in the U.S., there are approximately 400,000 coronary artery bypasses and 460,000 peripheral artery bypasses performed each year. Autografts are the gold-standard treatment. However, approximately 1/3 of these patients are unable to take this treatment because of limited autologous resources. Nondegradable grafts (e.g., PET and ePTFE) have been alternative to the autografts over the years, but they perform poorly in small arteries (< 6 mm) due to thrombosis, stenosis, and low patency rate. On the other hand, bioresorbable grafts have been proposed for in situ arterial regeneration using the host regenerative capacities. The complications occurred in the nondegradable grafts can be minimized. However, none of the currently existing biodegradable polymers have produced a clinically useful resorbable graft. In this proposal, we seek to synthesize new biodegradable functional polyester elastomers and use to engineer fully resorbable synthetic grafts with tunable degradation, mechanical properties, and hydrophilicity. We expect the fully remodeled grafts can grow along with native arteries, which is particularly important for pediatric patients. There are three main objectives in this proposal. Objective 1: Design, synthesis and characterization of the biodegradable functional polyester elastomers using endogenous and biocompatible monomers. Objective 2: Engineer anti-thrombotic fibrous grafts with tunable degradation and mechanical properties. Objective 3: Evaluation of candidate grafts in rat abdominal aorta interposition models for in situ arterial regeneration. Data from this project will be used to optimize the graft parameters for large animal studies in the future, given a quicker degradation and slower regenerative capacities in large animals. Undergraduate students including underrepresented students will be recruited and trained to conduct research in this project, such as material synthesis and characterizations, graft fabrication and characterizations, cell culture studies, and tissue section, staining and data analyses, among others.