Studying Interface Behavior of Blood and Degradable Magnesium Stent

 简介(申请人提供)：动脉粥样硬化是最常见的心脏病类型，也是导致心脏病发作的常见原因。动脉粥样硬化是由沿心脏动脉内壁沉积的斑块引起的，它使动脉变窄，限制血流。支架可以被插入动脉中，以保持动脉畅通。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而导致的再狭窄、晚期血栓形成、永久性物理刺激、有毒金属离子释放、血栓栓塞症和局部慢性炎症。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内提供暂时的机械整合，然后慢慢地被人体吸收。这种支架可以减少晚期支架血栓形成，通过计算机断层扫描或磁共振(镁的密度与骨密度相似)改善病变成像，促进对同一部位的重复治疗(无论是手术还是经皮)，恢复血管运动，避免Struts的侧支阻塞。然而，由于缺乏关于降解金属表面与周围血液和组织之间相互作用的详细信息，这些潜在的重要装置的开发受到阻碍。这项建议是为了研究可生物降解的镁基支架，为下一代支架技术做准备。一种经过适当设计的微流体设备可以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，只需使用少量血液。体外研究将提供有关血液对镁支架临床成功的影响的新知识。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-我们将检验假设，即微流控芯片中的不同剪应力将模拟体内的生理流动条件，并允许一致的定量测量镁的降解，(2)比较模型系统中镁和不锈钢的生理响应-关于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潜力的量化值，(3)为了评估可生物降解的镁的栓塞潜力-我们将检验镁降解产物是可溶的，而不是颗粒，并且不太可能构成血栓风险。这一应用利用了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，并为治疗动脉粥样硬化开辟新的战略。

 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.