Despite being a highly efficacious treatment for coronary and peripheral artery disease, the use of arterial stents has clinically significant limitations. Stent restenosis secondary to neointimal hyperplasia and stent thrombosis due to delayed arterial healing remain the primary limitations. The neointimal response has been dramatically reduced by drug-eluting stents (DES). However, the antiproliferative agents eluted by DES delay re-endothelialization and impair endothelial function. To overcome these challenges, we have developed a novel liquid cast nitric oxide (NO)-eluting biodegradable stent. The overall goal of this proposal is to study this novel NO-eluting biodegradable stent using our specialty triple-balloon catheter in vivo. We hypothesize that this technology will safely reduce stent restenosis and thrombosis compared to conventional stent platforms. Accordingly, our specific aims are to: 1) determine the optimal conditions to polymerize the NO-eluting liquid stent in vivo in a porcine iliac artery injury model using our specialty catheter~ 2) assess the hemodynamic and biologic compatibility of the NO-eluting liquid stent compared to DES and bare metal stents (BMS) ~ and 3) assess the efficacy of the NO-eluting liquid stent in reducing restenosis and stent thrombosis compared to DES and BMS. Our biodegradable poly (diol citrate) stent will deliver NO, a vasoprotective molecule that will vasodilate the freshly angioplastied artery thereby combating elastic recoil, and simultaneously promote long-term vascular healing by inhibiting neointimal hyperplasia, platelet adhesion, and stimulating endothelial cell growth. We have already demonstrated the biocompatibility of our polymer in vivo, optimized our NO-eluting polymer for photo-polymerization ex vivo, demonstrated sufficient and customizable mechanical stent properties, successfully cast stents in porcine arteries ex vivo, and developed and assembled multiple prototype triple balloon catheters with industry engineers. It is now time to evaluate this innovative stent technology in a preclinical animal model in vivo. This stent technology has the potential to overcome the shortcomings of existing commercially available metal stents as well as preformed biodegradable stents. Thus, development of this novel and innovative therapy will directly challenge the existing paradigm of using permanent metal stents to treat severe atherosclerosis and could have a large impact on patient care.

Public Health Relevance

The development of a drug-eluting biodegradable liquid cast arterial stent will lead to a radical departure in the treatment of atherosclerosis. To our knowledge, this is the first proposal to create a biodegradable arterial stent that forms in the body from a liquid prepolymer and is tailored to the patient's individual anatomy. Given the widespread nature of atherosclerosis, and the prevalence of arterial stenting, this innovative translational research has the potential to impact millions of Americans and has tremendous relevance to public health as it will change the way we think about promoting arterial health following vascular interventions.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL118976-02
Application #
8695111
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Meadows, Tawanna
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60611