异质金属对医用镁金属及其植入物腐蚀降解行为的影响与调控机制研究

The current studies on biodegradable magnesium and its alloys are focusing on the self-degradation behaviors along with the control methods. However, it is highly possible that the magnesium implants are used clinically together with other different metals, such as titanium alloys. As a result, the galvanic corrosion will probably occur due to a huge potential difference between magnesium and other metal, and then the degradation behavior of magnesium will be changed accordingly. Unfortunately, until now no report can be found about the galvanic corrosion of biodegradable magnesium coupled with other metallic implants in the physiological environment, thus there show some risk in the clinical applications of magnesium implant devices. Therefore, in the present study the effect and mechanism of other metals on biodegradable Mg and its implants will be researched systematically. By means of the metals widely used in clinics (such as titanium alloy) and the biodegradable magnesium metals (such as high purity magnesium), the influences of compositions and microstructures of magnesium metals on the galvanic effects will be studied in vitro, aiming to select those magnesium metals with the lowest galvanic corrosion trend. Then the corrosion patterns of magnesium under different structures of galvanic couples (e.g. distance of galvanic couples, and surface area ratios) are detected to obtain the control mechanism of weight loss, strength deterioration and facture failure of magnesium implants during degradation. Finally, the in vivo galvanic degradation behavior of magnesium will be researched by implanting devices (e.g. screws) made of magnesium and other metal together into some different animals, obtaining the law of degradation and failure mechanism of Mg implants in vivo, in order to provide the scientific proofs to guarantee safety of biodegradable magnesium applications in surgeries.

针对生物医用可降解镁金属材料的研究都着重关注镁合金本身的降解行为和调控方法，但镁医疗器械极有可能面临与其他异种金属植入物共同存在的情况，这些异质金属与镁的电位差巨大，可能产生电偶腐蚀效应，从而深刻改变镁的降解行为与机制，但这方面研究目前还是空白，给镁植入物的安全有效性带来巨大风险。因此，本项目拟系统开展异质金属对医用镁金属及其植入物的腐蚀降解行为与调控机制的研究。以临床常用的多种金属（如：钛合金等）和可降解吸收的镁金属（如：高纯镁等）为对象，研究其化学成分、显微组织结构对电偶腐蚀倾向的影响，优选出具有较低电偶腐蚀敏感性的医用镁材料；研究电偶对的间距、表面积比值等结构特征对镁的腐蚀降解性能影响规律，掌握其质量丢失、力学衰减和断裂失效的有效调控途径；并通过骨钉等多种镁金属与异质金属器械在动物体内的共同植入实验，获得在动物体内的腐蚀降解和失效规律，为镁金属及其植入物的临床安全使用提供科学依据。

可降解镁金属在骨科和介入血管支架的临床应用已经开展，未来实际临床应用中存在镁金属植入医疗器械与异质金属（如钛合金、不锈钢等）器械共同植入的情况，面临因电偶腐蚀效应可能大大加速镁的腐蚀降解的问题，但目前还没有这方面的深入的研究，这对镁植入物安全使用带来巨大风险。本项目针对这一问题系统地开展了研究工作。.首先，将医用高纯镁分别与三种异质金属（镁合金AZ91、不锈钢316L和纯钛TA2）直接接触共同浸泡在PBS模拟溶液中，研究异质金属对镁的质量损失、力学性能以及微区形态的影响。研究发现高纯镁在与三种异质金属连接后，腐蚀速率较单独浸泡都有明显提升（316L组＞TA2组＞AZ91组＞单独浸泡），主要与两种金属的自腐蚀电位差相关。高纯镁试样在引入异质金属后，在腐蚀速率明显提升的同时，随着腐蚀时间推移，腐蚀速率逐渐减缓。将浸泡4d的镁样品进行力学性能测试，发现单独浸泡衰减到144.112MPa，与AZ91连接后衰减到110.855MPa，与TA2连接后衰减到81.225MPa，与316L连接后衰减到93.813MPa，力学衰减程度与腐蚀加剧程度基本一致。.其次，开展了动物体内植入实验研究，对异质金属影响医用镁植入物的腐蚀规律进行了进一步验证。研究将高纯镁螺钉与纯钛螺钉分别间距5mm和10mm植入大鼠股骨中，通过micro-CT结果发现异质金属植入8周可以加速高纯镁金属降解，并减少新生骨生成。因此，镁与异质金属共同植入时保持一定的距离对于保持镁金属的机械和生物学特性至关重要。.第三，运用异质金属加速镁腐蚀的规律，促进镁可控释放更多氢气起到抗肿瘤的作用。将医用镁与钛连接以后，与肿瘤细胞共培养，发现不同条件下的氢气释放速率对肿瘤细胞生长有着不同程度的抑制效果。这对未来发展具有良好抗肿瘤功能的医用镁金属植入物具有重要启发。.总之，经过本项目的系统研究，发现了体内及体外异质金属作用下医用镁的腐蚀降解行为的巨大变化，得到了异质金属作用下医用镁的力学衰减的量化曲线，为相关镁金属植入物的临床安全有效使用奠定了一定的科学基础。