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.

摘要 动脉疾病动脉疾病，如动脉粥样硬化，其特征是动脉壁上的斑块堆积，因此对 血液流动的连续性，由于其对工业化国家健康的巨大影响，具有极大的社会利益，在工业化国家 肥胖率很高。虽然侵入性手术并不可取，但它们往往是确保患者生存的关键。这个 全世界每年有500万个冠状动脉支架植入人体动脉。 有耐心的。这导致了几个严重的副作用的出现。一种无害的生物可吸收金属支架 随着时间的推移，侵蚀可以将与永久支架相关的正常慢性风险降至最低。 由生物可吸收材料制成的支架在完成作为血管的任务后被人体腐蚀和吸收。 支架，使支架动脉恢复正常功能。这一概念可以通过工程实现。 支架保持机械性能和完整性至少4-6个月，然后被分解、代谢和 身体无害的排泄，使给药的血管具有健康的内皮，正常的血管运动和 没有植入物。因此，生物可吸收支架的使用打破了惰性植入物的长期范式，开启了一种独特的 在已经支架的血管节段进行第二次支架手术的机会。更进一步，缩窄的 每10,000名新生儿中就有3-4人患有主动脉，占所有先天性心脏病的5%-10%。有支架的血管 无法与孩子一起成长，导致再狭窄。因此，在婴幼儿中，曾经使用过生物可吸收支架 血管消失后，血管能够自然生长到成年，避免了重复的连续支架扩张手术。 锌(锌)合金优于目前公认的可生物降解聚合物、镁和铁材料，具有近 理想的腐蚀率和可接受的生物相容性。过去几年的研究证明，少量合金化 添加添加剂使强度提高2.5-3倍，腐蚀均匀，为完全可生物吸收的锌铺平了道路。 基座支架。此外，配方的弹性范围(弹性范围=弹性模数/极限抗拉强度) 锌合金含量为0.19-0.27%。这是一个重要的材料参数，描述了弹性后坐的程度 支架置入。这些锌合金的弹性范围值与316L不锈钢(~0.17%)和L605钴合金相当。 铬合金(0.16−0.32%)，优于目前使用的Ti-6Al-4V和Ti-Mo合金(0.72−0.85% 制造永久性支架。为了验证非常有前景的锌合金用于生物可吸收支架的应用， 拟议的研究计划将在腹主动脉腔内进行ApoE/-转基因致动脉粥样硬化的体内测试 评估小鼠的降解行为、新生内膜的厚度和组成，以及在致动脉粥样硬化中的毒性 环境。然后，使用顶级生物相容性合金，研究人员将设计、制作和测试编织支架。 基于以下标准：易于交付、高膨胀率、改进的机械完整性、统一 腐蚀性和理想的使用时间。