Studying Interface Behavior of Blood and Degradable Magnesium Stent

 描述（由申请人提供）：动脉粥样硬化是最常见的心脏病类型，也是心脏病发作的常见原因。动脉粥样硬化是由斑块沿心脏动脉内壁沿着沉积引起的，其使动脉变窄并限制血液流动。支架可以插入动脉以保持动脉通畅。然而，与这些永久性金属结构相关的风险包括由于长期内皮功能障碍导致的再狭窄、晚期血栓形成、永久性物理刺激、有毒金属离子释放、血栓栓塞和局部慢性炎症。我们将研究可生物降解金属（镁合金）在支架中的应用。这些合金可以在最初的几个月提供暂时的机械整合，然后慢慢被吸收到体内。这种支架可以减少晚期支架血栓形成，改善计算机断层扫描或磁共振（镁的密度与骨密度相似）的病变成像，促进对同一部位的重复治疗（手术或经皮），恢复血管舒缩和免于支柱造成的侧支阻塞。然而，这些潜在的重要设备的发展受到阻碍，缺乏详细的信息之间的相互作用的降解金属表面和周围的血液和组织。本提案旨在研究可生物降解的镁基支架，为下一代支架技术奠定基础。适当设计的微流体装置可以仅使用少量血液在生理剪切应力范围内同时评估降解镁表面上的血栓形成潜力。体外研究将为支架的临床成功提供血液对镁支架影响的新知识。拟议研究的具体目标如下：（1）为了比较镁基和不锈钢的表面降解行为-我们将测试以下假设：微流体芯片中的不同剪切应力将模拟体内生理流动条件并允许镁降解的一致定量测量，（2）比较模型系统中对镁和不锈钢的生理反应-假设血小板沉积和镁合金腐蚀之间的相关性的新知识将提供血栓形成的定量值，潜在性，（3）评估可生物降解镁的栓塞可能性-我们将检验镁降解产物是可溶性的而不是颗粒，并且不太可能造成栓塞风险的假设。该应用利用了Yeoheung Yun博士在生物材料科学方面的专业知识，将启动支架设计和使用的重大转变，并为动脉粥样硬化的治疗开辟新的策略。

 DESCRIPTION (provided by applicant): 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.