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.

项目总结 动脉粥样硬化性冠状动脉疾病(CAD)和外周动脉疾病(PAD)是 美国严重的发病率、死亡率和高昂的医疗费用。由于以下原因，此问题将继续增长 糖尿病的流行，因为糖尿病患者患动脉粥样硬化的风险增加，而 可能会有有利的治疗结果。血管内治疗，如放置金属支架， 已经被气球扩张的血管会打开堵塞，恢复血流。然而，这些疗法是 受到相对较高的再狭窄率的困扰，这被归因于支架的永久存在。 聚合物生物可吸收血管支架(BVSS)通过以下方式成为解决这些问题的潜在方案 提供初始支持以防止后坐，并缓慢降解以恢复血管运动并消除残留 可能导致再狭窄的异物。然而，聚合物BVS难以制造(制造 它们价格昂贵，设计控制有限)，由聚合物如聚(L-丙交酯)制成，这些聚合物 导致血栓形成并引起氧化组织损伤，从而加剧炎症。此外，正如在 FDA批准的BVS从雅培血管吸收GT1的情况下，支柱厚度必须大于 150μm，脚手架具有足够的强度以防止容器反冲并容纳聚合物 含有抗再狭窄药物以防止支架再次闭塞的涂层。临床研究表明，这一点 支架厚度是裸露金属支架的2倍，导致血栓发生率高。 小直径动脉(&lt；2.5毫米)和主要不良心脏事件，限制了它们的广泛使用 设备由于其庞大的配置文件。Ameer和Sun的研究团队一直在开发一种液体柠檬酸盐- 基于生物材料(CBB)，与被称为微连续液体的3D打印技术兼容 界面制作(μ剪辑)。CBB是可降解的，已被证明具有抗血栓和 抗氧化剂。这些特性是血管支架所需要的。这项研究提案的目的是 开发一种低调、药物洗脱、生物相容性和机械功能的柠檬酸盐基BVS。我们 假设通过μClip制造的低调柠檬酸盐基BVS将比大调BVS表现更好 体内吸收GT1 BVS。其具体目的是：1)在体外和活体动物模型上表征低密度脂蛋白。 使用μ夹子制作的药物洗脱BVSS的轮廓，以及2)评估3D打印的药物洗脱BVSS的安全性和有效性。 代谢综合征动脉粥样硬化猪体内BVSS的洗脱。具体地说，我们将调查通畅性， Ossabaw小型猪冠状动脉内BVS的生物相容性和吸收 概述了人类冠状动脉粥样硬化和代谢综合征。