Low-Profile 3D-Printed Radiopaque Bioresorbable Vascular Scaffolds

薄型 3D 打印不透射线生物可吸收血管支架

• 批准号: 10093122
• 负责人: Guillermo Antonio Ameer
• 金额: $ 76.57万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10093122
• 关键词: 3D Print; Antioxidants; Arteries; Atherosclerosis; Biocompatible Materials; Biology; Blood Vessels; Blood flow; Caliber; Cardiac; Cardiology; Cardiovascular system; Citrates; Clinical Research; Coagulation Process; Coronary Arteriosclerosis; Coronary artery; Devices; Diabetes Mellitus; Dimensions; Drug Delivery Systems; Endothelium; Epidemic; Event; FDA approved; Family suidae; Formulation; Health Care Costs; Human; Image; In Vitro; Incidence; Inflammation; Ink; Liquid substance; Mechanics; Metabolic syndrome; Metals; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patients; Peripheral arterial disease; Pharmaceutical Preparations; Polymers; Procedures; Production; Property; Research; Research Proposals; Residual state; Risk; SDZ RAD; Safety; Science; Stents; Techniques; Technology; The Sun; Thick; Thrombosis; Time; Tissues; Treatment outcome; Withdrawal; base; biodegradable polymer; biomaterial compatibility; cost; design; diabetic; drug standard; hemocompatibility; iliac artery; improved outcome; in vivo; mechanical properties; mortality; multidisciplinary; porcine model; prevent; restenosis; scaffold; thrombogenesis; vasomotion

PROJECT SUMMARY Atherosclerotic coronary artery disease (CAD) and peripheral artery disease (PAD) are responsible for significant morbidity, mortality, and high healthcare costs in the USA. This problem will continue to grow due to the diabetes epidemic as people with diabetes are at increased risk of developing atherosclerosis and less likely to have favorable treatment outcomes. Endovascular therapies such as placement of a metal stent that has been dilated by a balloon will open the blockage and restore blood flow. However, these therapies are plagued by relatively high restenosis rates, which have been attributed to the permanent presence of the stent. Polymeric bioresorbable vascular scaffolds (BVSs) have emerged as a potential solution to these problems by providing initial support to prevent recoil and slowly degrading to restore vasomotion and eliminate residual foreign materials that may contribute to restenosis. However, polymeric BVSs are difficult to fabricate (making them costly with limited design control) and are made from polymers such as poly(L-lactide) that are thrombogenic and cause oxidative tissue damage resulting in exacerbated inflammation. In addition, as in the case of the FDA-approved BVS Absorb GT1 from Abbott Vascular, the strut thickness has to be greater than 150 μm for the scaffold to have sufficient strength to prevent vessel recoil and to accommodate a polymer coating that contains an anti-restenotic drug to prevent stent re-occlusion. Clinical studies suggest that this strut thickness, which is 2 times larger than that of bare metal stents, leads to a high incidence of thrombosis in small-diameter arteries (<2.5 mm) and major adverse cardiac events, limiting the wide spread use of these devices due to their large profile. The Ameer and Sun research teams have been developing a liquid citrate- based biomaterial (CBB) that is compatible with a 3D printing technique referred to as micro continuous liquid interface production (μCLIP). CBBs, which are degradable, have been shown to be thromboresistant and antioxidant. These properties are desirable for vascular stents. The objective of this research proposal is to develop a low-profile, drug-eluting, biocompatible and mechanically functional citrate-based BVS. We hypothesize that a low-profile citrate-based BVS fabricated via μCLIP will perform better than the large-profile Absorb GT1 BVS in vivo. The specific aims are to: 1) Characterize, in vitro and in vivo in a rabbit model, low- profile drug-eluting BVSs fabricated using μCLIP, and 2) Assess the safety and efficacy of 3D-printed, drug- eluting BVSs in atherosclerotic swine with metabolic syndrome. Specifically, we will investigate the patency, biocompatibility, and resorption of the BVS in coronary arteries of the Ossabaw miniature pig, which recapitulates human coronary atherosclerosis and metabolic syndrome.

项目摘要 动脉粥样硬化冠状动脉疾病（CAD）和外周动脉疾病（PAD）负责 美国的大量发病率，死亡率和高医疗保健费用。由于 随着糖尿病患者患动脉粥样硬化的风险增加，而糖尿病的流行则增加 可能具有有利的治疗结果。血管内疗法，例如放置金属支架 已经通过气球扩张将打开阻塞并恢复血流。但是，这些疗法是 相对较高的再狭窄率困扰，这归因于支架的永久存在。 聚合物生物可吸收的血管支架（BVSS）已成为解决这些问题的潜在解决方案 提供初始支持以防止后坐力和缓慢退化以恢复血管舒张症并消除残留 可能导致再狭窄的外来材料。但是，聚合BVS难以制造（制作） 它们具有有限的设计控制），由聚合物（例如聚合物）制成 血栓形成并引起氧化组织损伤，导致注射恶化。另外，就像在 FDA批准的BVS的病例从Abbott Vascular吸收GT1，Strut厚度必须大于 脚手架的150μm具有足够的强度以防止容器后坐力并容纳聚合物 包含含有抗归化药物以防止支架重钉的涂层。临床研究表明这一点 支撑厚度是裸金属支架的2倍，导致血栓形成很高 小直径动脉（<2.5毫米）和重大的不良心脏事件，限制了这些事件的广泛使用 设备由于其庞大的轮廓。 Ameer和Sun研究团队一直在开发柠檬酸液体 - 基于生物材料（CBB）与3D打印技术兼容，称为微连续液体 界面生产（μClip）。可降解的CBB已被证明是动孔的， 抗氧化剂。这些特性对于血管支架是可取的。这项研究建议的目的是 开发低调，洗脱，生物相容性和机械功能性的基于柠檬酸盐的BV。我们 假设通过μClip制造的低调柠檬酸盐BV会比大型Pile曲更好 在体内吸收GT1 BV。具体目的是：1）在兔模型中表征，体外和体内，低 - 使用μClip制造的药物洗脱BVS和2）评估3D打印药物的安全性和效率 用代谢综合征在动脉粥样硬化猪中洗脱BVSS。具体来说，我们将调查通畅， 生物相容性和BVS在Ossabaw微型猪的冠状动脉中的分辨率，该动脉 概括人类冠状动脉粥样硬化和代谢综合征。