基于微流控芯片的镁合金降解与血管内皮重建交互作用的研究

Biomedical magnesium (Mg) alloy as a new type biodegradable stent material to support blood vessels shows a promissing application prospect. The degradation of Mg alloy and endothelial reconstruction restrict and interact with each other. However, the above problems are investigated in a single factor, two-dimensional and static way by most of the existing research. Here, we will aim to reconstruct accurate and controllable vascular microenvironment in vitro with microfluidic chip technology, and mimic its physical and biochemical factors. The degradation behaviors of Mg alloy under the synergistic action of multiple parameters will be studied, and the dynamic degradation model as well as degradation mechanism of Mg alloy will be established and analysis. Furthermore, the key factors that affect the degradation behaviors of Mg alloy will be revealed so as to control its degradation process precisely. We will also study the effect of Mg alloy degradation on vascular endothelial reconstruction and explore the cellular and molecular mechanisms of tissue regeneration. Meanwhile, the interaction between Mg alloy and vascular endothelium as well as its regulation mechanism will be elucidated, and the safety of materials and the effectiveness of vascular repair and functional reconstruction will be established. Overall, the relevant material and biological informations during the process of dynamic degradation of Mg alloy and vascular endothelial reconstruction canl be in-situ monitored and on-line analyzed, which provides a new perspective and method for studying the restenosis and its regulation mechanism.

生物医用镁合金作为新型可降解血管支架材料具有良好的应用前景。镁合金降解与血管内皮重建之间因交互作用而彼此影响、相互制约，现有技术与方法大多只能通过单因素、二维以及静态的方式对上述问题进行研究。本项目将利用微流控芯片技术，在体外重建精确、可控的血管微环境，模拟血管环境中的物理及生化因素，研究多参数协同作用下的镁合金降解行为，建立镁合金动态降解模型并解析其降解机制，揭示影响镁合金降解行为的关键因素，实现对镁合金降解过程的精确控制；同时研究镁合金降解对血管内皮重建过程的影响，探索组织再生的细胞、分子机制，阐明镁合金降解与血管内皮重建的交互作用规律及其调控机制，建立材料安全性以及血管修复与功能重建的有效性评价。本项目的开展，将实现对镁合金的动态降解及血管内皮重建过程中相关材料学和生物学信息的原位监测和在线分析，为研究支架内再狭窄机理及其调控机制提供新的探索视角和研究手段。

镁及其合金具有良好的力学性能、可降解性和生物相容性，是一种革命性的医用金属材料。相对于传统医用金属材料，镁及其合金的应用更新了传统的将医用金属作为生物惰性材料使用的思想，巧妙地利用其降解性能实现了其作为短期植入物的应用。如何使镁合金植入物以可控方式实现其组织重建与修复功能，提高宿主细胞响应及组织生长速率、血管网络快速形成能力，缩短组织再生、修复与重建周期，是目前阶段镁合金器械研发与应用的关键问题。本项目通过有限元建模分析的方法，结合先进的微流控技术，对镁合金血管夹及可回收血管支架的结构进行了优化设计，并设计了一种用于闭合大穿孔的内窥镜多击发夹子施加器系统，研究了镁合金的体外降解行为、细胞相容性及血液相容性，建立了材料设计-性能调控-器件开发之间的关系，为开发性能可控的镁合金植入器械、促进其临床应用提供了新的思路和更高效的技术手段。