Magnesium and alloying elements on vascular cells health

 描述(申请人提供)：可生物降解的镁(镁)基合金是骨科和心血管支架应用中最有前途的生物材料之一。本研究的目的是探讨支架支架中常用的镁及合金元素对内皮细胞健康的影响。与传统生物材料相比，镁具有生物可降解性和良好的生物相容性等优点。量身定制的镁合金有可能消除永久支架材料的高晚期再狭窄和血栓形成。此外，一些镁基支架目前正在进行临床试验，结果令人鼓舞。然而，关于这些镁离子和合金元素是如何影响内皮细胞功能和活性的，这仍然是我们目前知识基础上的一个空白。这一建议的中心假设是，镁离子和合金元素将以浓度依赖的方式改变内皮细胞的功能和活性。对合金的健康反应所需的关键内皮细胞终点，包括良好的细胞存活率和增殖、不受损害的细胞迁移率、保存无反应以及限制NADPH氧化酶或线粒体活性氧物种(ROS)的形成。本研究中包括的元素是那些在支架应用中常用的元素，即镁、钙、锌、铝、锆、Y、和Ge、ND和Gd。目的1是确定这些单独的合金元素对内皮细胞的活性、增殖、ROS和NO释放的影响。目的2是确定这些单独的合金元素对内皮细胞的细胞骨架重组、移动性、连接和屏障功能的影响。目标 3是确定这些合金元素如何改变内皮细胞的基因表达谱。综上所述，这项拟议的研究具有重要而独特的意义，因为它将有助于回答这些合金元素的最大添加量是多少，以便在改善机械和腐蚀性能的同时，将其对内皮细胞的有害影响降至最低。这将有助于填补现有的关于这些单独元素对内皮细胞的安全性和毒性的知识，并为未来基于这些合金的理想心血管植入物的设计提供指导。

 DESCRIPTION (provided by applicant): Biodegradable magnesium (Mg)-based alloys are one of the most promising biomaterials for orthopedic and cardiovascular stent applications. The objective of this proposal is to investigate the effects of Mg and alloying elements commonly used in stent scaffolds on endothelial cells' health. Mg possesses many advantages over conventional biomaterials, such as biodegradability and good biocompatibility. Tailored Mg alloys have the potential for eliminating high rate of late restenosis and thrombogenesis in permanent stent materials. Moreover, some Mg-based stents are currently under clinical trials with encouraging outcomes. However, it still remains as a gap in the current base of our knowledge on how these individual Mg ion and alloying elements affect endothelial cell functions and activities. The central hypothesis of this proposal is that Mg ion and alloying elements will alter the cellular functions and activities of endothelial cells in a concentration dependent manner. Critical endothelial cell endpoints that are needed for a healthy response to alloys including good cell viability and proliferation, unimpaired cell mobility, preserved NO responses, and limited NADPH oxidase or mitochondrial reactive oxygen species (ROS) formation. The elements included in this study are those commonly used in stent applications, namely, Mg, Ca, Zn, Al, Zr, Y, and Gy, Nd, and Gd. Aim 1 is to determine the effects of these individual alloying elements on the viability, proliferation, and ROS and NO release of endothelial cells. Aim 2 is to determine the effects of these individual alloying elements on the cytoskeletal reorganization, mobility, and junctions and barrier function of endothelial cells. Aim 3 is to determine how each of these alloying elements alters the gene expression profile of endothelial cells. Taken together, the proposed study is significant and unique because it will help answer the question what is the maximum amount of these alloying elements should be added into the alloy such that mechanical and corrosion properties are improved while their deleterious effects on endothelial cells are minimal. It will contribute to filling the existing ga in our knowledge about the safety and toxicity of each of these individual elements on endothelial cells, and provide guidance in future design of ideal cardiovascular implants based on these alloys.