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

摘要 使用镁(Mg)的新一代可生物吸收金属支架目前正在开发和测试中。 从临床上看。研究小组受到最近的临床数据的激励，以探索局部变化在 动脉粥样硬化性炎症微环境可使镁合金的生物腐蚀发生相当大的变化。 此外，研究小组还对了解金属的腐蚀产物如何影响新生内膜很感兴趣。 进步。因此，该项目的目标是：i)阐明生理上与动脉粥样硬化有关的 炎性微环境影响镁基材料的腐蚀过程，II)决定 镁腐蚀是否可以在新生内膜的进展中施加可测量的变化，使用先进的 APOE-/-KO小鼠模型的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性炎症细胞(泡沫细胞)，这些细胞 与斑块进展有关，当暴露于临床使用的镁时，将表征其细胞行为 合金(WE43)和其他临床相关的镁合金(AZ31、WE22、ZA41)。然后，团队将确定他们的 通过分泌的反应物种来调节微流控降解环境可以起到相当大的作用 AIM中镁合金腐蚀进程的变化。对于AIMS II和III，研究小组将植入镁合金 在致动脉粥样硬化的APOE/-转基因小鼠中。AIM II将专注于使用基本成像系统，这将允许 用于高分辨率和高灵敏度的原位元素检测。团队将描述两国之间的关系 种植体衍生的微量金属和炎症的原位存在。AIM III将探索全球关系 镁合金、新血管内膜特征和生物变量之间的关系。在这里，镁合金的腐蚀速度在 患病的动物将被描述，并与健康的动物对照进行比较。 总体而言，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会影响 镁合金的腐蚀速度；2)新生内膜的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实现。 这项工作将有助于破解镁支架在临床上的失效机制，有助于生物工程和生物工程技术的发展。 临床医生发现了更耐腐蚀和生物相容的镁合金。

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.