经导管瓣膜镍钛合金支架镍离子释放体外模拟及细胞毒性评价  

Study on in Vitro Nickel Ion Release and Cytotoxicity Assessment for Transcatheter Aortic Valve Containing Nitinol Stent

作　　者：刘丽[1] 刘丽红[2] 付海洋[1] 柯林楠[1] 胡立刚[2] Liu Li;Liu Lihong;Fu Haiyang;Ke Linnan;Hu Ligang(National Institutes for Food and Drug Control,Beijing 102629,China;State Key Laboratory of Environmental Chemistry and Ecotoxicology,Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China)

机构地区：[1]中国食品药品检定研究院,北京102629 [2]中国科学院生态环境研究中心,环境化学与生态毒理学重点实验室,北京100085

出　　处：《中国药事》2021年第9期1029-1035,共7页Chinese Pharmaceutical Affairs

基　　金：国家重点研发计划(编号2016YFC1102304)。

摘　　要：目的:研究经导管瓣膜镍钛合金支架动态疲劳中镍离子释放及其潜在体外细胞毒性,为该类创新医疗器械产品的临床前安全性评价提供参考,为推动医疗器械创新发展提供技术支撑。方法:以经导管瓣膜镍钛合金支架为研究对象,利用脉动疲劳试验模拟支架临床植入10年的情况(4亿次疲劳测试),研究其动态疲劳过程中镍离子的释放情况,并利用细胞模型评估所释放镍离子的潜在毒性效应。结果:随着镍钛合金支架疲劳试验时间的增加,测试溶液中镍离子浓度增大,测试液中镍离子最大浓度为0.075 mg·L^(-1)。利用不同浓度梯度的镍离子溶液对L929细胞进行细胞毒性试验,当离子浓度为小于等于6.25 mg·L^(-1)时,无体外细胞毒性,当镍离子浓度大于等于12.5 mg·L^(-1)时,有潜在的细胞毒性。结论:经4亿次动态疲劳测试后(模拟临床使用10年)经导管瓣膜支架中镍离子的释放量低于安全限值,无体外细胞毒性。Objective: This study is to investigate the release of nickel ions from TAV(Transcatheter Aortic Valve) and its potential in vitro cytotoxicity during the dynamic fatigue process of transcuttal valvular nickeltitanium alloy stents, so as to provide references for preclinical safety evaluation of innovative medical devices,and to provide technical support for promoting the development of medical devices. Methods: In this study, the pulsatile fatigue test was used to simulate clinical implantation for 10 years(400 million fatigue tests) with the transductal valvular nickel-titanium alloy stent. The release of nickel ions during the dynamic fatigue process of the stent was studied, and the potential toxic effects of the released nickel ions were evaluated by using the cell model. Results: The results showed that the concentration of nickel ion in the test solution increased with the increase of fatigue test time and the maximum concentration of nickel ion in the test solution was 0.075 mg·L^(-1).The cytotoxicity test of L929 cells was carried out by using nickel ion solutions with different concentration gradients. There was no in vitro cytotoxicity when the concentration of nickel ion was less than or equal to 6.25 mg·L^(-1) and potential cytotoxicity was observed when the nickel concentration was equal to 12.5 mg·L^(-1).Conclusion: The release of nickel ion from transcuttal valve stents was lower than the safety limit after 400 million dynamic fatigue tests and there was no cytotoxicity in vitro.

关 键 词：经导管瓣膜 镍钛合金支架 镍离子释放 动态疲劳测试 细胞毒性 风险评估 

分 类 号：R95[医药卫生—药学] R912