Novel surface-modified bioresorbable zinc-based stent materials

新型表面改性生物可吸收锌基支架材料

• 批准号: 9935151
• 负责人: Yadong Wang
• 金额: $ 45.61万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9935151
• 关键词: Adhesions; Alloys; Arteries; Benchmarking; Biocompatible Materials; Blood Platelets; Blood Vessels; Cardiovascular system; Cell Survival; Cell model; Characteristics; Clinical; Coagulation Process; Coronary; Coronary heart disease; Corrosion; Data; Differentiation and Growth; Doppler Ultrasound; Effectiveness; Electron Microscopy; Elements; Endothelium; Engineering; Evolution; Exhibits; Failure; Fluorides; Generations; Goals; Health; Hemolysis; Histologic; Immersion; Immune response; Implant; In Vitro; Industrialization; Inflammation; Inflammatory Response; Iron; Lead; Life; Magnesium; Mechanics; Metals; Methodology; Modeling; Modification; Natural regeneration; Operative Surgical Procedures; Outcome; Patients; Performance; Pilot Projects; Polymers; Process; Property; Proteins; Rattus; Recovery; Resistance; Roentgen Rays; Safety; Sampling; Stainless Steel; Stents; Strontium; Surface; Survival Rate; Tensile Strength; Testing; Thrombosis; Tissues; Zinc; absorption; base; biomaterial compatibility; cell growth; design; ductile; emission spectrometry; experience; falls; healing; hemocompatibility; implantation; improved; in vivo; in vivo monitoring; mechanical properties; medical implant; melting; microCT; next generation; novel; nutrition; physical property; prevent; restenosis; stem cell growth

Approximately 5 million coronary stents are implanted world-wide each year. Most clinical stents are made of anti-corrosion metals such as stainless steels. Life-long presence of these stents, however, often falls short in preventing complications including in-stent restenosis (i.e. re-narrowing of arteries) and late thrombosis (i.e. clotting). Alternatives (e.g. biodegradable materials) that could deliver the life-long treatment for coronary blockade have long been sought. Here, a novel bioresorbable zinc (Zn)-strontium (Sr) alloy is proposed as a promising candidate for stent. Strong preliminary results demonstrated the potential and feasibility of this proposed study. It is believed that the Zn-based stent implants will eliminate the need for secondary surgeries and avoid many complications associated with current permanent implants. In addition, compared with other degradable stent materials, i.e., polymers or magnesium (Mg), tailored Zn alloys with right configuration offer stronger strength and ductility, slower degradation matching the pace of tissue healing, non-hydrogen evolution and better biocompatibility. Zn itself is an essential element for health while alloying element Sr is a nutrition element as well and can significantly enhance the mechanical and corrosion properties. The goals of this project are to determine the most effective compositions of novel binary Zn-Sr alloys and test their effectiveness as a coronary stent material, both in vitro and in vivo, in three specific aims. Aim 1: Prepare surface modified Zn- Sr binary alloys to tailor the material properties to accepted values of tensile strength, elongation to failure, and corrosion rate as stent implants. Implants are prepared by melting, rolling and extruding, and their microstructure, physical and mechanical properties are studied using electron microscopy, X-ray diffractometory, atomic emission spectrometry, tensile and uniaxial compression tests, immersion tests, and electrochemical tests, etc. Aim 2: Evaluate the biocompatibility of implants in vitro systematically. Implants will be examined on protein absorption, hemocompatibility, primary vascular cell viability and growth, vascular stem cell growth and differentiation, and direct endothelialization using in vitro cellular models. Aim 3: Evaluate implants corrosion, safety and interactions with vascular tissues in vivo using a rat arterial implantation model. Wire samples will be used to mimic the stent struts and their in vivo performances will be examined in a rat vascular model. Doppler ultrasound and microCT will be used to monitor the in vivo corrosion process, and histological examination will be performed to assess the inflammation and immune response.

全世界每年大约植入500万个冠状动脉支架。大多数临床支架由 不锈钢等抗腐蚀金属。然而，这些支架的终身存在通常福尔斯不足， 预防包括支架内再狭窄（即动脉再狭窄）和晚期血栓形成（即， 凝血）。可为冠状动脉疾病提供终身治疗的替代品（例如，可生物降解材料） 长期以来一直寻求封锁。在此，提出了一种新的生物可吸收的锌（Zn）-锶（Sr）合金， 有希望的支架候选者。强有力的初步结果证明了这一潜力和可行性 建议的研究。据信，锌基支架植入物将消除二次手术的需要 并且避免了与当前永久性植入物相关的许多并发症。此外，与其他 可降解支架材料，即，聚合物或镁（Mg），定制的锌合金与正确的配置提供 更强的强度和延展性，与组织愈合速度相匹配的较慢降解，无氢析出 和更好的生物相容性。锌本身是人体健康的必需元素，而合金元素锶是一种营养元素 元素，并可以显着提高机械和腐蚀性能。本项目的目标 确定新型二元Zn-Sr合金的最有效成分，并测试其作为一种 冠状动脉支架材料，在体外和体内，在三个特定的目标。目的1：制备表面改性的Zn- Sr二元合金，以将材料性能调整到可接受的抗拉强度、伸长率、 失效和腐蚀率。植入物通过熔融、辊压和挤出制备， 用电子显微镜、X射线衍射仪、扫描电镜、透射电镜、扫描电镜、 衍射、原子发射光谱、拉伸和单轴压缩试验、浸泡试验，以及 目的2：系统评价植入物的体外生物相容性。 将检查植入物的蛋白质吸收、血液相容性、原代血管细胞活力和生长， 血管干细胞生长和分化，以及使用体外细胞模型的直接内皮化。目标三： 使用大鼠动脉评价植入物的腐蚀性、安全性和与体内血管组织的相互作用 植入模型将使用导丝样品模拟支架支柱，并评估其体内性能 在大鼠血管模型中检查。多普勒超声和microCT将用于监测体内腐蚀 将进行组织学检查以评估炎症和免疫应答。