Novel Bioresorbable Vascular Scaffolds with Uniform Biodegradation

具有均匀生物降解性的新型生物可吸收血管支架

• 批准号: 10930188
• 负责人: Jaroslaw W Drelich
• 金额: $ 46.17万
• 依托单位: MICHIGAN TECHNOLOGICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10930188
• 关键词: Acceleration; Address; Adult; Alloys; Anti-Inflammatory Agents; Aortic coarctation; Apolipoprotein E; Arteries; Atherosclerosis; Behavior; Benchmarking; Biodegradation; Birth; Blood Vessels; Blood flow; Cells; Characteristics; Child; Chromium; Chronic; Clinical; Coagulation Process; Cobalt; Congenital Heart Defects; Coronary; Corrosion; Crystallography; Developed Countries; Diameter; Dilatation - action; Disease; Elasticity; Elements; Endothelium; Engineering; Ensure; Environment; Excretory function; Exhibits; Family suidae; Fatigue; Formulation; Fracture; Geometry; Grain; Health; Human; Image; Implant; In Vitro; Infant; Inflammatory; Iron; Lasers; Lesion; Liquid substance; Literature; Location; Magnesium; Mechanics; Metabolic Clearance Rate; Metals; Minor; Modulus; Mus; Obesity; Patients; Pattern; Periodicity; Pharmaceutical Preparations; Phase; Physiological; Pilot Projects; Porosity; Predisposition; Procedures; Process; Property; Radial; Repeat Surgery; Research; Research Personnel; Resistance; Risk; Risk Reduction; Services; Shapes; Smooth Muscle Myocytes; Stainless Steel; Stents; Stress; Structure; Techniques; Technology; Tensile Strength; Testing; Texture; Thick; Thinness; Thrombosis; Time; Toxic effect; Transgenic Organisms; Vascular Diseases; Zinc; abdominal aorta; absorption; biodegradable polymer; biomaterial compatibility; density; design; experience; flexibility; iliac artery; improved; in vitro testing; in vivo evaluation; innovation; interest; manufacture; mechanical properties; metallicity; mouse model; notch protein; novel; pressure; programs; prototype; restenosis; scaffold; side effect; vasomotion

Summary Artery disease, such as atherosclerosis characterized by a build-up of plaque on arterial walls, so detrimental to the continuity of blood flow, is of great societal interest due to its drastic impact on health in industrialized nations, where obesity rates are high. While invasive procedures are not desirable, they are often crucial to ensuring patient survival. The 5 million coronary stents administered world-wide each year remain present in the human artery for the lifetime of the patient. This has resulted in the emergence of several serious side effects. A bioresorbable metal stent that harmlessly erodes away over time could minimize the normal chronic risks associated with permanent stents. Stents made of bioresorbable materials are corroded and absorbed by the body after completing their task as vascular scaffolding, allowing the stented arteries to restore their normal function. The concept may be achieved by engineering stents that retain mechanical properties and integrity for at least 4 - 6 months before being broken down, metabolized, and harmlessly excreted by the body, leaving the administrated vessel with a healthy endothelium, normal vasomotion and free of implant. Therefore, the use of bioresorbable stents breaks the long paradigm of inert implants and opens a unique opportunity for a second stenting procedure in already scaffolded segments of the blood vessels. Further, coarctation of the aorta occurs in 3-4 in 10,000 births and accounts for 5 to 10 percent of all congenital heart defects. The stented vessel is unable to grow with the child, leading to restenosis. Therefore, in infants and children, once the bioresorbable stent disappears, the vessel is able to naturally grow until adulthood, avoiding repeated surgeries for serial stent dilatation. Zinc (Zn) alloys are superior to currently accepted biodegradable polymers, magnesium and iron materials, with a near- ideal corrosion rate and acceptable biocompatibility. The research in the last few years proves that minor alloying additions to enhance both the strength by 2.5-3 times and corrosion uniformity paves the way to a fully bioresorbable Zn- based stent. Additionally, the elastic ranges (elastic range = elastic modulus/ultimate tensile strength) for the formulated Zn alloys are 0.19 - 0.27%. This is an important material parameter that describes the extent of elastic recoil following stent deployment. These Zn alloys elastic range values are on par with 316L stainless steel (~0.17%) and L605 cobalt- chromium alloys (0.16−0.32%) and are superior to Ti-6Al-4V and Ti-Mo alloys (0.72−0.85%) currently used for manufacturing permanent stents. To validate the very promising Zn alloys for bioresorbable stent applications, the proposed research program will conduct in vivo testing in the abdominal aorta lumen of ApoE -/- transgenic atherogenic mice to evaluate their degradation behavior, thickness and make-up of neointima, and toxicity in an atherogenic environment. Then, using the top biocompatible alloys, researchers will design, prototype, and test braided scaffolds based on the following criteria: ease of deliverability, a high expansion ratio, improved mechanical integrity, uniform corrosion, and desirable service time.

概括 动脉疾病，例如动脉粥样硬化，其特征是在动脉壁上积聚斑块，因此对 血流的连续性，由于对工业化国家的健康影响的巨大影响，具有极大的社会利益。 肥胖率很高。尽管侵入性程序并不可取，但它们通常对于确保患者生存至关重要。这 每年在全球范围内管理的500万个冠状动脉支架在人类动脉中仍然存在 病人。这导致出现了几种严重的副作用。无害 随着时间的流逝，侵蚀可以最大程度地减少与永久支架相关的正常慢性风险。 由生物可用材料制成的支架在完成任务后被身体腐蚀和吸收 脚手架，使支架动脉恢复其正常功能。该概念可以通过工程来实现 在分解，代谢和 人体无害超越，使行政船具有健康的内皮，正常的血管症和 没有植入物。因此，生物可吸收支架的使用破坏了惰性int液的长长范式，并打开了独特的 在已经脚手架的血管段中进行第二个支架程序的机会。此外，缩合 主动脉在10,000个出生中发生3-4，占所有先天性心脏缺陷的5％至10％。支架的船只 无法与孩子一起成长，导致再狭窄。因此，在婴儿和儿童中，一旦生物可吸收支架 消失，容器能够自然生长直到成年，避免了连续支架扩张的反复手术。 锌（Zn）合金优于当前可接受的可生物降解聚合物，镁和铁材料，几乎 理想的腐蚀速率和可接受的生物相容性。最近几年的研究证明了较小的合金 增加了强度的增加2.5-3次，腐蚀均匀性为完全生物吸收的Zn-铺平了道路 基于支架。此外，弹性范围（弹性范围=弹性模量/终极拉伸强度） Zn合金为0.19-0.27％。这是一个重要的材料参数，描述了弹性后坐力的程度 支架部署。这些Zn合金弹性范围值与316升不锈钢（约0.17％）和L605钴 - 铬合金（0.16-0.32％）优于TI-6AL-4V和TI-MO合金（0.72-0.85％） 制造永久支架。为了验证可生物可吸收支架应用的有希望的Zn合金， 拟议的研究计划将在APOE的腹主动脉腔中进行体内测试 - / - 转基因动脉粥样硬化 小鼠评估其降解行为，厚度和新内膜的构成以及动脉粥样硬化中的毒性 环境。然后，使用顶部生物相容性合金，研究人员将设计，原型和测试编织的脚手架 基于以下标准：易于交付，高膨胀比，改善的机械完整性，均匀 腐蚀和理想的服务时间。