Magnesium and alloying elements on vascular cells health

 描述（由申请人提供）：生物可降解镁（Mg）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镁和合金元素在支架材料中的应用对内皮细胞健康的影响。镁具有生物可降解性和良好的生物相容性等优点。定制镁合金具有消除永久支架材料中晚期再狭窄和血栓形成的高发生率的潜力。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，它仍然是一个空白，在目前的基础上，我们的知识，这些个别镁离子和合金元素如何影响内皮细胞的功能和活动。该建议的中心假设是，镁离子和合金元素将以浓度依赖性方式改变内皮细胞的细胞功能和活性。对合金的健康反应所需的关键内皮细胞终点，包括良好的细胞活力和增殖、未受损的细胞移动性、保留的NO反应以及有限的NADPH氧化酶或线粒体活性氧（ROS）形成。本研究中包括的元素是支架应用中常用的元素，即Mg、Ca、Zn、Al、Zr、Y和戈伊、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力，增殖和ROS和NO释放的影响。目的2是确定这些合金元素对内皮细胞骨架重组、流动性、连接和屏障功能的影响。目的 3是确定这些合金元素如何改变内皮细胞的基因表达谱。总之，所提出的研究是重要和独特的，因为它将有助于回答这样一个问题，即这些合金元素的最大量应该添加到合金中，使得机械和腐蚀性能得到改善，同时它们对内皮细胞的有害影响最小。这将有助于填补现有的ga在我们的知识的安全性和毒性的每一个这些个别元素对内皮细胞，并提供指导，在未来的设计理想的心血管植入物的基础上，这些合金。

 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.