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Principal Investigator: Jose Francisco Huizar
Organization: VA VETERANS ADMINISTRATION HOSPITAL
Fiscal Year: 2024
Funding agency: Veterans Affairs
Cardiovascular disease is the leading cause of death in developed countries. A common treatment for
atherosclerotic cardiovascular disease is placement of an arterial stent. While stent technology has improved
over the years, including the development of drug-eluting stents, failure rates remain high and current
technologies are associated with significant challenges. Thus, there is a great need for new stent technology
that will improve patient outcomes following percutaneous cardiac and peripheral vascular interventions. We
propose to develop an innovative, paradigm-shifting stent technology that will obviate the need for
placement of permanent metal stents in the arterial system for the treatment of severe atherosclerosis.
Specifically, we propose to develop a solid biodegradable stent from a liquid drug-eluting polymer by
photo-polymerizing the stent in the body using a specially designed triple balloon catheter. This
“designer therapy” will be tailored to the contours of the individual artery and coat the entire surface of the
artery, significantly reducing the thrombogenic potential at the site of injury and providing the greatest surface
area for drug delivery. Our biodegradable poly(dodecanediol citrate) (PDDC) stent will deliver nitric oxide
(NO), a vasoprotective molecule that will vasodilate the freshly angioplastied artery, thereby combating elastic
recoil. The custom-formed stent will also promote long-term vascular healing by simultaneously inhibiting
neointimal hyperplasia and platelet adhesion, and stimulating endothelial cell growth. The stent will have
mechanical properties specific for the pulsatile, compliant arterial system. Lastly, the stent will degrade over
time, leaving a healthy, prosthetic-free, polymer-free environment in its place. Thus, our hypothesis is that a
liquid-cast, NO-eluting, biodegradable stent will have a superior patency rate compared to
conventional metal stents following balloon angioplasty by inhibiting thrombosis and neointimal
hyperplasia, and stimulating re-endothelialization. Through our multidisciplinary team of investigators and
industry engineers, we have already demonstrated the feasibility of our project through preliminary data. It is
now time to focus on developing and optimizing the drug releasing capacity of the polymeric stent and
conducting the in vivo preclinical studies necessary to translate this technology to the clinical arena. Thus, the
specific aims of this project are: 1) Develop and optimize a NO-eluting, liquid-cast PDDC stent using
diazeniumdiolate and S-nitrosothiol chemistry; 2) Evaluate and tune the mechanical properties of the NO-
eluting, liquid-cast PDDC stent ex vivo; 3) Examine the safety and efficacy of the NO-eluting, liquid-cast PDDC
stent in vivo. Our novel approach challenges the existing paradigm for arterial stenting and will lead to a
radical departure in the treatment of atherosclerotic occlusive disease. Through our preliminary data, we have
demonstrated the feasibility of this project. Given the burden of atherosclerotic disease in the veteran
population, the studies in this proposal will result in a new technology that will be translated to improved
veteran health.
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