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

基本信息

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
项目类别：
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

项目摘要

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，其特征是动脉壁上积聚斑块，因此疼痛血液流动的连续性，由于其对工业化国家的健康产生巨大影响而具有重大社会意义，其中肥胖率很高，虽然侵入性手术并不可取，但它们通常对于确保患者的生存至关重要。每年全世界有 500 万个冠状动脉支架在人的一生中保留在人体动脉中。这导致了一些无害的生物可吸收金属支架的出现。随着时间的推移，腐蚀消失可以最大限度地减少与永久性支架相关的正常慢性风险。由生物可吸收材料制成的支架在完成其作为血管的任务后被人体腐蚀并吸收支架，让支架动脉恢复正常功能这一概念可以通过工程来实现。支架在分解、代谢和分解之前至少保留 4 - 6 个月的机械性能和完整性被身体无害地排出体外，使施用的血管具有健康的内皮、正常的血管舒缩和因此，生物可吸收支架的使用打破了惰性植入物的长期范式，开辟了独特的途径。在已经架设的血管段上进行第二次支架置入手术的机会。每 10,000 名新生儿中有 3-4 名患有主动脉疾病，占所有先天性心脏病的 5% 至 10%。无法与孩子一起成长，导致再狭窄，因此，在婴儿和儿童中，一旦使用生物可吸收支架。消失后，血管能够自然生长直至成年，避免了连续支架扩张的重复手术。锌（Zn）合金优于目前公认的可生物降解聚合物、镁和铁材料，具有接近理想的腐蚀速率和可接受的生物相容性过去几年的研究证明了轻微的合金化。添加物将强度提高 2.5-3 倍，腐蚀均匀性为完全生物可吸收的 Zn- 铺平了道路。另外，所配制的支架的弹性范围（弹性范围=弹性模量/极限拉伸强度）。锌合金为 0.19 - 0.27% 这是一个重要的材料参数，描述了弹性反冲的程度。这些锌合金的弹性范围值与 316L 不锈钢 (~0.17%) 和 L605 钴相当。铬合金 (0.16−0.32%)，优于目前用于制造的 Ti-6Al-4V 和 Ti-Mo 合金 (0.72−0.85%) 为了验证用于生物可吸收支架应用的非常有前途的锌合金，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小鼠评估其降解行为、新内膜的厚度和组成，以及致动脉粥样硬化的毒性然后，研究人员将使用顶级生物相容性合金设计、制作原型并测试编织支架。基于以下标准：易于交付、高膨胀比、改进的机械完整性、均匀腐蚀和理想的使用寿命。