Tuesday, February 7, 2023
2/7/2023
PROJECT SUMMARY Atherosclerotic coronary artery disease (CAD) and peripheral artery disease (PAD) are responsible for significant morbidity, mortality, and high healthcare costs in the USA. This problem will continue to grow due to the diabetes epidemic as people with diabetes are at increased risk of developing atherosclerosis and less likely to have favorable treatment outcomes. Endovascular therapies such as placement of a metal stent that has been dilated by a balloon will open the blockage and restore blood flow. However, these therapies are plagued by relatively high restenosis rates, which have been attributed to the permanent presence of the stent. Polymeric bioresorbable vascular scaffolds (BVSs) have emerged as a potential solution to these problems by providing initial support to prevent recoil and slowly degrading to restore vasomotion and eliminate residual foreign materials that may contribute to restenosis. However, polymeric BVSs are difficult to fabricate (making them costly with limited design control) and are made from polymers such as poly(L-lactide) that are thrombogenic and cause oxidative tissue damage resulting in exacerbated inflammation. In addition, as in the case of the FDA-approved BVS Absorb GT1 from Abbott Vascular, the strut thickness has to be greater than 150 µm for the scaffold to have sufficient strength to prevent vessel recoil and to accommodate a polymer coating that contains an anti-restenotic drug to prevent stent re-occlusion. Clinical studies suggest that this strut thickness, which is 2 times larger than that of bare metal stents, leads to a high incidence of thrombosis in small-diameter arteries (<2.5 mm) and major adverse cardiac events, limiting the wide spread use of these devices due to their large profile. The Ameer and Sun research teams have been developing a liquid citrate- based biomaterial (CBB) that is compatible with a 3D printing technique referred to as micro continuous liquid interface production (µCLIP). CBBs, which are degradable, have been shown to be thromboresistant and antioxidant. These properties are desirable for vascular stents. The objective of this research proposal is to develop a low-profile, drug-eluting, biocompatible and mechanically functional citrate-based BVS. We hypothesize that a low-profile citrate-based BVS fabricated via µCLIP will perform better than the large-profile Absorb GT1 BVS in vivo. The specific aims are to: 1) Characterize, in vitro and in vivo in a rabbit model, low- profile drug-eluting BVSs fabricated using µCLIP, and 2) Assess the safety and efficacy of 3D-printed, drug- eluting BVSs in atherosclerotic swine with metabolic syndrome. Specifically, we will investigate the patency, biocompatibility, and resorption of the BVS in coronary arteries of the Ossabaw miniature pig, which recapitulates human coronary atherosclerosis and metabolic syndrome.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
