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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

基本信息

批准号：
10329908
负责人：
Guillermo Antonio Ameer
金额：
$ 67.7万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10329908
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 Persons 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

项目摘要

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.

项目概要动脉粥样硬化性冠状动脉疾病 (CAD) 和外周动脉疾病 (PAD) 是导致美国的发病率、死亡率很高，医疗费用也很高。这个问题将继续加剧，因为糖尿病流行，因为糖尿病患者患动脉粥样硬化的风险增加，且患病率降低可能会取得良好的治疗效果。血管内治疗，例如放置金属支架已通过球囊扩张将打开堵塞并恢复血流。然而，这些疗法都是受到相对较高的再狭窄率的困扰，这归因于支架的永久存在。聚合物生物可吸收血管支架（BVS）已成为解决这些问题的潜在解决方案提供初始支撑以防止反冲并缓慢降解以恢复血管舒缩并消除残留可能导致再狭窄的异物。然而，聚合物 BVS 很难制造（使得它们成本高昂且设计控制有限）并且由聚（L-丙交酯）等聚合物制成血栓形成并引起氧化组织损伤，导致炎症加剧。此外，如在对于经 FDA 批准的 Abbott Vascular 的 BVS Absorb GT1，支柱厚度必须大于 150 μm 使支架具有足够的强度以防止血管反冲并容纳聚合物含有抗再狭窄药物以防止支架重新闭塞的涂层。临床研究表明，这支架厚度比裸金属支架大2倍，导致血栓发生率高小直径动脉（<2.5 毫米）和主要不良心脏事件，限制了这些的广泛使用设备由于其大的外形。 Ameer 和 Sun 研究团队一直在开发一种液体柠檬酸盐- 基于生物材料（CBB），与称为微连续液体的 3D 打印技术兼容界面制作（μCLIP）。 CBB 是可降解的，已被证明具有抗血栓性抗氧化剂。这些特性对于血管支架来说是理想的。本研究计划的目的是开发一种低调、药物洗脱、生物相容且具有机械功能的基于柠檬酸盐的 BVS。我们假设通过 μCLIP 制造的低轮廓柠檬酸盐 BVS 将比大轮廓表现更好体内吸收 GT1 BVS。具体目标是：1）在兔模型中进行体外和体内表征，低- 分析使用 μCLIP 制造的药物洗脱 BVS，以及 2) 评估 3D 打印的药物洗脱 BVS 的安全性和有效性在患有代谢综合征的动脉粥样硬化猪中洗脱 BVS。具体来说，我们将调查通畅性， Ossabaw 小型猪冠状动脉中 BVS 的生物相容性和吸收，概括了人类冠状动脉粥样硬化和代谢综合征。