Deciphering the relationship between bioresorbable magnesium alloy corrosion and the inflammatory microenvironment of the neotinima

总结 目前正在开发和测试使用镁（Mg）的新一代生物可吸收金属支架 临床上该研究小组受到最近临床数据的激励，以探索局部变化是否在 动脉粥样硬化炎症微环境可以在镁合金的生物腐蚀中产生相当大的转变。 此外，该团队有兴趣了解金属的腐蚀产物如何影响新生内膜 进展因此，本项目的目标是：I）阐明生理相关的动脉粥样硬化 炎症微环境影响镁基材料的腐蚀进程，和II）确定 镁腐蚀是否可以在新生内膜的进展中产生可测量的变化，使用先进的 在APOE-/- KO小鼠模型中进行元素成像和大规模数据收集。 首先，将运行体外共培养模型，使用关键的动脉粥样硬化炎性细胞（泡沫细胞）， 与斑块进展有关，并将表征其暴露于临床使用的镁时的细胞行为 合金（WE 43）和其他临床相关镁合金（AZ 31、WE 22、ZA 41）。然后，团队将确定他们的 通过分泌的反应性物质调节微流体降解环境可以发挥相当大的作用 目的I中镁合金腐蚀进程的变化。对于目标II和III，团队将植入镁合金 在致动脉粥样硬化的APOE-/-转基因小鼠中。Aim II将专注于使用元素成像系统， 用于高分辨率和高灵敏度的原位元素检测。该团队将描述 原位存在植入物衍生的微量金属和炎症。Aim III将探索全球关系 镁合金、新生内膜特征和生物学变量之间的关系。在这里，镁合金的腐蚀速率在 将描述患病动物并与健康动物对照进行比较。 总的来说，这些目标将使研究小组能够确定1）病变的新生内膜微环境是否影响 镁合金的腐蚀速率，以及2）新生内膜进展是否与镁合金的生物腐蚀有关。这 将通过使用大规模组织学数据收集和降维技术来完成。 这项工作将有助于破译镁支架在临床上的失效机制，并帮助生物工程师和 临床医生发现了更耐腐蚀和生物相容性更好的镁合金。

Summary A new generation of bioresorbable metal stents using magnesium (Mg) is currently being developed and tested clinically. The research team is motivated by recent clinical data to explore whether local changes in the atherosclerotic inflammatory microenvironment can exert a considerable shift in the biocorrosion of Mg alloys. Additionally, the team is interested in understanding how corrosion products from the metals influence neointimal progression. Therefore, the objectives of this project are to: I) clarify how physiologically relevant atherosclerotic inflammatory microenvironments affect the corrosion progression of Mg based materials, and II) determine whether Mg corrosion can exert measurable changes in the progression of the neointima, using advanced elemental imaging and large-scale data collection in an APOE-/- KO mouse model. First, an in vitro co-culture model will be run, using key atherosclerotic inflammatory cells (foam cells) that are implicated in plaque progression and will characterize their cellular behavior when exposed to clinically used Mg alloys (WE43) and other clinically relevant Mg alloys (AZ31, WE22, ZA41). The team will then determine if their modulation of the microfluidic degradation environment via secreted reactive species can exert considerable shifts in the corrosion progression of Mg alloys in Aim I. For Aims II and III, the team will implant the Mg alloys in atherogenic APOE-/- transgenic mice. Aim II will focus on using an elemental imaging system, which will allow for in situ element detection at high resolution and sensitivity. The team will describe the relationship between the in-situ presence of implant derived trace metals and inflammation. Aim III will explore the global relationships between Mg alloys, neointimal characteristics, and biological variables. Here, the corrosion rate of Mg alloys in diseased animals will be described and compared to healthy animal controls. Overall, these aims will allow the team to determine whether 1) diseased neointimal microenvironments influence the corrosion rate of Mg alloys, and 2) if neointimal progression is related to the biocorrosion of Mg alloys. This will be accomplished by using large scale histological data collection, and dimensional reduction techniques. This work will aid in deciphering the failure mechanisms of Mg stents in the clinic and help bioengineers and clinicians identify more corrosion resistant and biocompatible Mg alloys.