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.
A common treatment for severe atherosclerotic cardiovascular disease is endovascular 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. 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 custom-formed stent will prevent thrombosis and restenosis while simultaneously promoting endothelialization and long-term vascular health. Given the burden of atherosclerotic cardiovascular disease in the veteran population, the studies in this proposal will result in a novel technology that will significantly improve veteran health.
