Biodegradable Metal Stent Alloys for Vascular Applications

用于血管应用的可生物降解金属支架合金

• 批准号: 10643743
• 负责人: Jeremy Goldman
• 金额: $ 73万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-12 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643743
• 关键词: Alloys; Anticoagulants; Arteries; Biocompatible Materials; Biodegradation; Biological; Blood Cells; Blood Platelets; Blood Vessels; Blood coagulation; Cardiac; Cardiovascular Diseases; Cell physiology; Chromium; Clinical; Cobalt; Copper; Corrosion; Data; Devices; Dimensions; Elements; Environment; Enzyme Precursors; Equipment Malfunction; Exhibits; Failure; Goals; Grain; Heart Diseases; Hydroxides; Implant; In Vitro; Inflammatory Response; Ions; Iron; Legal patent; Life; Magnesium; Mechanics; Metals; Modeling; Modification; Morbidity - disease rate; Oxides; Patients; Performance; Peripheral; Persons; Pharmaceutical Preparations; Polymers; Preclinical Testing; Process; Property; Stainless Steel; Stents; Structure; Sulfides; Surface; Surface Properties; Techniques; Technology; Testing; Thrombosis; Time; Translations; Vascular Diseases; Vascular System; Work; Zinc; biodegradable polymer; biomaterial compatibility; bioresorption; design; hemocompatibility; improved; in vivo; interest; manufacture; mechanical properties; metallicity; monocyte; mortality; nanosized; neutrophil; nitinol; nonhuman primate; preclinical study; prevent; response; restenosis; scaffold; thrombogenesis; thromboinflammation

PROJECT SUMMARY Cardiovascular disease remains the leading cause of morbidity and mortality in the US, despite decades of advancements in treatment, including stent coatings and anti-platelet therapies. The improvements in stent material technology progressed from bare metal stainless steel, cobalt-chromium, and nitinol (high thrombogenicity and high restenosis) to drug eluting polymer coated metals (lowered restenosis, but thrombogenic) to biodegradable polymers (potential to decrease restenosis, but still thrombogenic). Despite these incremental advances, thrombosis and in-stent restenosis all remain significant clinical obstacles, limiting the life-saving potential of stent applications in cardiac and peripheral arteries and requiring life-long prescription of anticoagulant and antiplatelet therapies for patients. Recently, biodegradable metals have garnered interest for stent applications to reduce thrombosis and restenosis. Biodegradable metal vascular stents must have sufficient mechanical strength to maintain an open lumen for at least 6 months, must be non-thrombogenic, prevent restenosis, and degrade between 6 months and 2 years, while maintaining cytocompatibility. Biodegradable metal stents bioresorb through corrosion by which the metal is converted to a more stable form, such as its oxide, hydroxide or sulphide state. Initial studies of biodegradable metals like iron (Fe), magnesium (Mg), and zinc (Zn) have shown promise in terms of mechanical properties and degradation rates. Importantly, the degradation products of these metals are biocompatible ions which contribute to cell functions. A single metal does not meet the requirements of a biodegradable metallic stent, yet metallic alloys and optimization of materials processing techniques can satisfy the stringent requirements. We have established the ability to design, manufacture, and test alloys with up to 5 metal alloying elements based on zinc and magnesium. Through our proposed work, the impact of critical processing steps (e.g., hot extrusion, cold drawing) on material properties, particularly microstructure, biodegradation rate, and biodegradation uniformity, will be determined. We will quantify the biological responses of pure and alloyed biodegradable metals to determine their performance in the vascular system, particularly emphasizing thrombosis, restenosis, and inflammatory responses to the alloyed metals and their degraded ions. In the present proposal, our goal is to develop biodegradable metal alloys that meet the strict mechanical and biologic requirements of vascular stents. The overall objective of this project is to identify alloying elements and material processing requirements for biodegradable metal materials that can suppress local thrombo-inflammatory responses by (1) developing and characterizing the mechanical, material, and surface properties of biodegradable metal alloys and (2) establishing the biocompatibility of biodegradable metals for vascular stent applications. Successful completion of this R01 will result in identification of biodegradable metal alloys that meet the mechanical and biological requirements of vascular stents, and set the stage for long-term pre-clinical testing.

项目摘要 尽管数十年 治疗方面的进步，包括支架涂层和抗血小板疗法。支架的改进 材料技术从裸露的金属不锈钢，钴 - 铬和奈蒂醇（高）发展（高 血栓形成性和高还原病）至洗脱聚合物涂层金属（降低再狭窄，但 血栓形成）到可生物降解的聚合物（可能降低再狭窄，但仍具有血栓形成）。尽管 这些增量的进步，血栓形成和内部再狭窄都保持着巨大的临床障碍，限制了 支架在心脏和外围动脉中施加寿命的潜力，并需要终身处方 患者的抗凝剂和抗血小板疗法的疗法。最近，可生物降解的金属引起了人们的兴趣 用于减少血栓形成和再狭窄的支架应用。可生物降解的金属血管支架必须具有 足够的机械强度保持开放式管腔至少6个月，必须是非表现的， 预防再狭窄，并在6个月至2年之间降解，同时保持细胞相容性。 可生物降解的金属支架通过腐蚀将金属转化为更稳定的形式的腐蚀， 例如其氧化物，氢氧化物或硫化物状态。对铁（FE），镁等可生物降解金属的初步研究 （MG）和锌（Zn）在机械性能和降解速率方面表现出了希望。重要的是， 这些金属的降解产物是有助于细胞功能的生物相容性离子。一种金属 不符合可生物降解的金属支架的要求，但金属合金和材料的优化 处理技术可以满足严格的要求。我们已经建立了设计的能力， 生产和基于锌和镁的最多5个金属合金元件的合金测试合金。通过我们的 拟议的工作，关键处理步骤（例如，热挤出，冷图）对材料特性的影响， 将确定微观结构，生物降解率和生物降解均匀性。我们将 量化纯和合金可生物降解金属的生物学反应，以确定其性能 血管系统，尤其强调血栓形成，再狭窄和对合金的炎症反应 金属及其降解离子。在本提案中，我们的目标是开发可生物降解的金属合金 满足血管支架的严格机械和生物学要求。该项目的总体目标是 确定可生物降解金属材料的合金元素和材料处理要求 通过（1）开发和表征机械，材料， 可生物降解金属合金的表面特性以及（2）建立可生物降解的生物相容性 血管支架应用的金属。成功完成此R01将导致确定 符合血管支架机械和生物学要求的可生物降解金属合金，并将 长期临床前测试的阶段。