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

描述（由申请人提供）：预计到2015年将有1.33亿美国人超过45岁，这是心脏病发病率增加的年龄。许多人需要支架（通过血管成形术将小金属网套植入未堵塞的动脉）。这个价值数十亿美元的行业，全球有超过200万患者，其中15%使用镍钛诺（NiTi Alloy）支架，最近销售额下降，部分原因是在相对简单的动脉阻塞的稳定患者中，每年约有1000人中有2人形成血栓。血栓形成是药物洗脱支架内突然形成的血块。因此，美国食品和药物管理局（Food and Drug administration）、美国心脏协会（American Heart Association）等机构呼吁研发新一代支架，采用新的设计和不同的合金，使其更灵活，更能适应动脉。因此，镍钛诺作为生物材料的未来取决于更好地理解镍钛诺表面如何保持稳定和惰性，同时保持灵活性和可加工性的机制。此外，镍钛诺表面的镍富集及其浸出必须加以控制，因为它对肝脏和肾脏具有致癌性和有害作用。镍也会导致坏死。因此，我建议对镍钛诺（Ni51Ti49）1-xTax系三元合金在0-20原子% Ta范围内进行标准的美国试验与材料学会（ASTM）动电位和恒电位腐蚀试验，评价其在生物介质中的耐蚀性。作为三元元素添加到niti合金中，已被证明具有x射线可见性、稳定性、耐腐蚀性和其他有益效果。电感耦合等离子体分析将用于监测Ni在生物介质中的释放。生物相容性将通过观察细胞在材料表面的生长情况来评估，并探索血液相容性[血小板扩散，蛋白质吸附，细胞增殖，炎症介质等]。镍钛诺表面将使用XRD， DSC， EPMA，拉曼光谱，SEM等进行表征。我认为，这项应用研究工作可以提高NiTi在冠状动脉和外周动脉中的体内安全性和性能，以及合金遭受极端腐蚀性的身体通道，最终导致先进的Nitinol合金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