Enhanced Biocompatibility of NiTi (NITINOL) via Surface Treatment and Alloying

描述(由申请人提供)：据预测，到2015年，45岁以上的美国人将达到1.33亿人，这是心脏病发病率增加的记录年龄。许多将需要支架(通过血管成形术将小金属网套植入通畅的动脉)。这个价值数十亿美元的行业在全球拥有200多万患者，其中15%使用镍钛合金支架，最近销售额下降，部分原因是相对简单的动脉阻塞的稳定患者每年每1000人中有2人发生血栓。血栓形成是药物洗脱支架内形成的一种突然的血液凝块。因此，美国食品和药物管理局、美国心脏协会和其他机构正在呼吁新一代支架、新设计和不同的合金，这些支架更灵活，对动脉的适应性更强。因此，镍钛作为生物材料的未来取决于对镍钛表面稳定和惰性的机制的更好理解，同时保持灵活性和可加工性。此外，由于镍的致癌性和对肝脏和肾脏的有害影响，必须控制镍的浓缩和从镍醇表面的浸出。镍也会导致坏死。因此，我建议在0-20原子%Ta范围内对NiInol(Ni51Ti49)1-xTax三元合金进行美国材料试验学会(ASTM)标准的动电位和恒电位腐蚀试验，以评价其在生物介质中的耐蚀性。在镍钛合金中添加三元元素Ta，已被证明具有X射线可见性、稳定性、耐腐蚀性等有益效果。电感耦合等离子体分析将用于监测生物介质中镍的释放。生物相容性将通过观察材料表面细胞的生长和探索血液相容性[血小板扩散、蛋白质吸附、细胞增殖、炎症介质等]来评估。镍钛合金的表面将用X射线衍射仪、差示扫描量热仪、电子探针、拉曼光谱、扫描电子显微镜等进行表征。我认为，这项应用研究工作可以改善镍钛合金的体内安全性和性能，因为它用于冠状动脉和外周动脉，以及用于合金遭受极端腐蚀的人体通道，最终导致先进镍钛合金的更广泛有效的医疗用途。

DESCRIPTION (provided by applicant): It is projected that by 2015 there will be 133 million Americans over 45, the age at which the increased incidence of heart diseases is documented. Many will require stents (small metal-mesh sleeves implanted in unclogged arteries by angioplasty). This multi-billion dollar industry, with over 2 million patients worldwide, 15% of whom use Nitinol (a NiTi Alloy) stents, has experienced a decline in sales recently, due in part to Thrombosis in about two out of 1000 per year in stable patients with relatively simple artery blockage. Thrombosis is a sudden blood clot that forms inside drug-eluting stents. As a result, the Food and Drug Adminstration, the American Heart Association, and others are calling for a new generation of stents, new designs and different alloys that are more flexible and more adaptable to the arteries. The future of Nitinol as a biomaterial therefore depends on a better understanding of mechanisms by which Nitinol surface can be rendered stable and inert, yet retain flexibility and machinability. Additionally, Ni enrichment and its leaching from the Nitinol surface must be controlled due to its carcinogenicity and deleterious effects in the liver and kidney. Ni also causes necrosis. Therefore, I propose to conduct standard American Society of Testing and Materials (ASTM) potentiodynamic and potentiostatic corrosion tests on the ternary alloys of Nitinol (Ni51Ti49)1-xTax system in the range of 0-20 atomic % Ta to evaluate the corrosion resistance in biological media. Ta, added as a ternary element in the NiTi-alloys, has been proven to impart X-ray visibility, stability, corrosion resistance and other beneficial effects. Inductively Coupled Plasma Analysis will be used to monitor Ni release in biological media. Biocompatibility will be assessed by observing the growth of cells on the material's surface and exploring blood compatibility [platelet spreading, protein adsorption, cell proliferation, inflammatory mediators, etc.] The Nitinol surfaces will be characterized using XRD, DSC, EPMA, Raman Spectroscopy, SEM, etc. I am of the opinion that this applied research effort could improve upon the in-vivo safety and performance profile of NiTi as used in coronary and peripheral arteries, as well as in bodily passageways where the alloy is subjected to corrosivity extremes, ultimately resulting in the even more widespread efficacious medical use of advanced Nitinol alloys