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: 10047332
• 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 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10047332
• 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 cells

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。大多数临床支架是由 防腐金属，例如不锈钢。然而，这些支架的终生存在往往达不到以下目的： 预防并发症，包括支架内再狭窄（即动脉再狭窄）和晚期血栓形成（即血栓形成） 凝血）。可以为冠状动脉提供终身治疗的替代品（例如可生物降解材料） 长期以来一直在寻求封锁。这里，提出了一种新型生物可吸收锌（Zn）-锶（Sr）合金作为 有前途的支架候选者。强有力的初步结果证明了这一点的潜力和可行性 提议的研究。据信，锌基支架植入将消除二次手术的需要 并避免与当前永久植入物相关的许多并发症。另外，与其他相比 可降解支架材料，即聚合物或镁 (Mg)、具有正确配置的定制锌合金 更强的强度和延展性、与组织愈合速度相匹配的更慢的降解、非析氢 以及更好的生物相容性。 Zn本身是健康必需元素，合金元素Sr是营养品 元素以及可以显着增强机械和腐蚀性能。该项目的目标 旨在确定新型二元 Zn-Sr 合金的最有效成分并测试其作为 冠状动脉支架材料，在体外和体内，具有三个特定目标。目标 1：制备表面改性 Zn- 锶二元合金可根据拉伸强度、伸长率的可接受值调整材料性能 支架植入物的失效和腐蚀率。植入物通过熔化、滚压和挤压制备， 使用电子显微镜、X 射线研究它们的微观结构、物理和机械性能 衍射法、原子发射光谱法、拉伸和单轴压缩测试、浸没测试和 目标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， 血管干细胞的生长和分化，以及使用体外细胞模型的直接内皮化。目标 3： 使用大鼠动脉评估植入物的腐蚀、安全性以及与体内血管组织的相互作用 植入模型。线材样品将用于模拟支架支柱，其体内性能将 在大鼠血管模型中进行检查。多普勒超声和微型CT将用于监测体内腐蚀 将进行过程和组织学检查以评估炎症和免疫反应。