Atherosclerosis is the most common type of heart disease and a common cause of heart attacks. Atherosclerosis is caused by plaque deposition along the inner walls of the arteries of the heart, which narrows the arteries and restricts blood flow. Stents can be inserted into arteries to keep them open. However, risks associated with these permanent metal structures include restenosis because of long-term endothelial dysfunction, late thrombosis, permanent physical irritation, toxic metal ion release, thromboembolism, and local chronic inflammation. We will investigate the use of biodegradable metals (magnesium alloys) in stents. These alloys can provide temporary mechanical integration for the first few months and then be slowly absorbed into the body. Such stents can reduce late stent thrombosis, improved lesion imaging with computed tomography or magnetic resonance (the density of magnesium is similar with the density of bone), facilitation of repeat treatments (either surgical or percutaneous) to the same site, restoration of vasomotion and freedom from side-branch obstruction by struts. However, development of these potentially important devices is hampered by the lack of detailed information concerning the interaction between the degrading metal surface and the surrounding blood and tissue. This proposal is to study biodegradable magnesium-based stents for the next generation of stenting technology. A properly engineered microfluidic device can simultaneously assess thrombogenic potential on a degrading magnesium surface over the range of physiological shear stresses using only a small volume of blood. In vitro studies will provide new knowledge on the effects of blood on magnesium stents for clinical success of stents.
The specific aims of the proposed studies follow; (1) to compare the surface degradation behavior of magnesium-based and stainless steel - we will test the hypothesis that varying shear stress in microfluidic chips will mimic in vivo physiological flow conditions and allow consistent quantitative measurement of magnesium degradation, (2) to compare physiological response to magnesium and stainless steel in the model system - the hypothesis that new knowledge of correlation between platelet deposition and the corrosion of magnesium alloys will provide quantitative value for thrombogenic potential, (3) to assess embolism potential of biodegradable magnesium - we will test the hypothesis that magnesium degradation products are soluble, rather than particulate, and unlikely to pose an embolism risk. This application, which leverages Dr. Yeoheung Yun's expertise in biomaterial science, will initiate a major shift in stent design and use, and open up new strategies for the treatment of atherosclerosis.
Tubular metal inserts, or stents, are the major treatment for atherosclerosis, a significant cause of heart attack. However, current stent technology is associated with long-term endothelial dysfunction, restenosis, late thrombosis, toxic metal ion release, thromboembolism and local chronic inflammation. This project will investigate the in vivo behavior of various magnesium alloys, with the goal of developing biodegradable metal stents that will mitigate many of these complications.
