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

解读生物可吸收镁合金腐蚀与新生细胞炎症微环境之间的关系

• 批准号: 10580115
• 负责人: Roger J. Guillory
• 金额: $ 17.48万
• 依托单位: MICHIGAN TECHNOLOGICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2023-08-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10580115
• 关键词: Acceleration; Address; Affect; Alloys; Animal Diseases; Aorta; ApoE knockout mouse; Arterial Fatty Streak; Attention; Biodistribution; Biological; Biomedical Engineering; Blood Vessels; Cells; Characteristics; Cholesterol; Clinic; Clinical; Clinical Data; Clinical Research; Coculture Techniques; Control Animal; Coronary Arteriosclerosis; Corrosion; Data Collection; Detection; Development; Dimensions; Disease; Disease Progression; Drug or chemical Tissue Distribution; Elements; Endothelium; Engineering; Environment; Exposure to; Failure; Foam Cells; Future; Generations; Histologic; Hyperplasia; Image; Implant; In Situ; In Vitro; Individual; Inflammation; Inflammatory; Knockout Mice; Macrophage; Magnesium; Measurable; Mediating; Metals; Microfluidics; Modeling; Mus; Patients; Physiological; Plasma; Process; Production; Reactive Nitrogen Species; Reactive Oxygen Species; Research; Resistance; Resolution; Running; Signal Transduction; Stents; Techniques; Technology; Testing; Tissues; Toxic effect; Trace metal; Transgenic Mice; Work; absorption; biomaterial compatibility; bioresorption; cell behavior; clinically relevant; cytotoxicity; design; imaging system; improved; in vivo; interest; large scale data; metallicity; mouse model; neointima formation; next generation; prevent; response; risk minimization; soft tissue; tissue repair

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.

概括 目前正在开发和测试新一代使用镁（MG）的生物渗透金属支架（MG） 临床。研究团队的动机是最近的临床数据，以探索当地的变化是否在 动脉粥样硬化的炎症微环境可以在MG合金的生物腐蚀中发生相当大的转变。 此外，该团队有兴趣了解金属的腐蚀产品如何影响新内膜 进展。因此，该项目的目标是：i）澄清生理上相关的动脉粥样硬化 炎性微环境影响基于MG的材料的腐蚀进展，ii）确定 MG腐蚀是否可以使用先进的 APOE - / - KO鼠标模型中的元素成像和大规模数据收集。 首先，将使用关键的动脉粥样硬化炎症细胞（泡沫细胞）进行体外共培养模型 与牙菌斑的进展有关，并在暴露于临床使用Mg时表征其细胞行为 合金（WE43）和其他临床相关的MG合金（AZ31，WE22，ZA41）。然后，团队将确定他们的 通过分泌的反应性物种对微流体降解环境的调节可以发挥相当大的作用 目标II II和III中的MG合金的腐蚀进展转移，团队将植入MG合金 在动脉粥样硬化 - / - 转基因小鼠中。 AIM II将专注于使用元素成像系统，这将允许 用于高分辨率和灵敏度的原位元素检测。团队将描述 植入物衍生的痕量金属和炎症的原位存在。 AIM III将探索全球关系 MG合金，新内膜特性和生物变量之间。在这里，MG合金的腐蚀速率 将描述患病动物并将其与健康的动物对照进行比较。 总体而言，这些目标将使团队能够确定1）患病的新内膜微环境影响 MG合金的腐蚀速率和2）如果新内膜进展与MG合金的生物腐蚀有关。这 将通过使用大规模的组织学数据收集和尺寸还原技术来完成。 这项工作将有助于解释诊所中MG支架的故障机制，并帮助生物工程师和 临床医生确定了更多的耐腐蚀性和生物相容性的MG合金。