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 balloon angioplasty followed by the placement of a metal stent can alleviate the symptoms of the disease by restoring blood flow through blocked arteries. However, these therapies are plagued by relatively high restenosis rates, which have been attributed to the permanent presence of the stent and malapposition due to improper matching of stent size to the artery’s dimensions. 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), are made from polymers such as poly(L lactide) that are known to cause oxidative tissue damage, a process that exacerbates inflammation, and are not completely visible to the physician performing the procedure. 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 in order 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 2-3 times larger than that of bare metal stents, leads to high incidence of thrombosis in small-diameter arteries (&lt; 2.5 mm), limiting the wide spread use of these devices due to their large profile. The Ameer and Sun research laboratories have been recently developing the concept of personalized BVSs by formulating a liquid citrate-based biomaterial to work as an “ink” for a 3D printing technique referred to as micro continuous liquid interface production (microCLIP). The objective of this research proposal is to develop a biomaterial ink (B-InkTM) formulation that will enable the printing of a low profile, drug-eluting, biocompatible and mechanically functional BVS that can be fully visualized in vivo using standard non-invasive clinical imaging modalities. The specific aims are to: 1) Fabricate and characterize, in vitro and in a rat stented abdominal aorta model, 3D-printed, low profile radiopaque BVSs, 2) Investigate the feasibility of incorporating anti-restenotic drugs into the B-inkTM formulation to fabricate drug-eluting BVS using microCLIP, and 3) Assess the safety and efficacy of 3D-printed BVSs in rabbit and coronary artery disease swine preclinical models.
|Effective start/end date||1/1/19 → 12/31/22|
- National Heart, Lung, and Blood Institute (R01HL141933-01A1)