Nanoparticle- Infused Radiopaque Absorbable Medical Device

纳米颗粒注入不透射线可吸收医疗器械

• 批准号: 10199005
• 负责人: Marites Pasuelo Melancon
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10199005
• 关键词: Adverse effects; Adverse event; Adverse reactions; Affect; Algorithms; American; Animals; Anticoagulants; Anticoagulation; Autopsy; Barium; Bismuth; Blood Circulation Time; Blood Vessels; Blood coagulation; Calcium; Cardiovascular Diseases; Cardiovascular system; Catheters; Chronic; Clinical; Coagulation Process; Complex; Contrast Media; Deep Vein Thrombosis; Deposition; Development; Devices; Diagnostic radiologic examination; Disadvantaged; Discrimination; Disease; Dose; Electrospinning; Elements; Embolism; Enhancers; Event; Excision; Exhibits; Failure; Fatigue; Filtration; Fluoroscopy; Fracture; Goals; Gold; Hemorrhage; Hospitalization; Human; Hydrolysis; Hypersensitivity; Image; Image Enhancement; Imaging Techniques; In Vitro; Infusion procedures; Intervention; Iodine; Lead; Life; Lung; Mechanics; Medical Device; Metals; Methods; Monitor; Nail plate; Operative Surgical Procedures; Organ; Orthopedics; Patients; Pharmacologic Substance; Physiological; Plague; Polymers; Population; Positioning Attribute; Prevention; Procedures; Property; Public Health; Pulmonary Embolism; Reporting; Research; Retrieval; Risk; Rod; Roentgen Rays; Signal Transduction; Stroke; Surgical sutures; System; Tantalum; Testing; Therapeutic Embolization; Thrombus; Time; Toxic effect; Trauma; Tungsten; Vena Cava Filters; Visualization; X-Ray Computed Tomography; X-Ray Film; Ytterbium; Zirconium; absorption; acute coronary syndrome; animal imaging; biodegradable polymer; biomaterial compatibility; cost; crystallinity; experimental study; flexibility; high risk; imaging modality; imaging properties; imaging study; improved; in vivo; interest; mathematical algorithm; medical implant; metallicity; mortality; nanoparticle; nephrotoxicity; novel; poly-4-dioxan-2-one; porcine model; prevent; prophylactic; routine imaging; success; time use; venous thromboembolism; zirconium oxide

PROJECT SUMMARY Venous thromboembolism (VTE) is the third most common cardiovascular illness after acute coronary syndrome and stroke. The first line of therapy for VTE is blood thinners; however, these agents are temporarily contraindicated for many at-risk VTE patients, such as those with major trauma and those who undergo complex surgeries, for whom bleeding is a concern. Inferior vena cava (IVC) filters are indicated in this population. Most IVC filters (70%) are intended to be retrieved after their indicated use; however, only 19%- 30% are removed. Unfortunately, complications mount when IVC filters are not removed, which can be very costly ($3,000-$12,000 for filter retrieval and ~$67,000 for treatment of complications). Therefore, resorbable IVC filters were developed, which provide critical protection during their required duration and then simply vanish from the body, thereby alleviating costly removal procedures and downstream complications. However, an important limitation of a resorbable IVC filter system is significant clot burden. Monitoring the absorption time and any significant clot burden with use of imaging techniques would greatly improve the efficacy of deep vein thrombosis treatment. In this study, we will develop of radiopaque absorbable filters that can be routinely imaged to offer a less expensive alternative to assessing filter integrity. Moreover, visualization of the filter under dual-energy computed tomography (DECT) would facilitate discrimination between two or more materials, such as nanoparticles (NPs), iodine, and calcium deposits, which could provide better image quality and quantification of the materials present in the filter. Specifically, we propose to incorporate NPs (made up of gold, bismuth, ytterbium, tantalum, tungsten, barium, and zirconium), into clinically available resorbable polydioxanone (PPDO) suture, investigate the effect of NP infusion within PPDO sutures in terms of mechanical strength, toxicity, and physico-chemical properties over a period of 10 weeks when subjected to human physiological conditions, and perform large animal imaging study using optimized DECT parameters to determine radiopacity, toxicity, and mechanical strength, as well as adverse reactions of image-enhanced suture during necropsies. We will also develop a mathematical algorithm for DECT for the quantification of the different high atomic (Z) number contrast materials infused within the PPDO. Our long-term goal is to develop a totally absorbable IVC filter, inexpensively deployed and monitored by conventional imaging methods that prevents pulmonary embolism for the recommended prophylactic period and then simply vanishes without intervention. The experiments outlined here will be critical to demonstrating the feasibility of using NPs as radiopaque material for DECT imaging embedded within this medical device. Successful development of imaging enhancers for IVC filters may also lead to widespread use of absorbable devices in other cardiovascular and orthopedic applications in which fixtures (such as plates, screws, nails, and rods) are needed only on a temporary basis.

项目概要 静脉血栓栓塞症（VTE）是继急性冠心病之后第三大常见的心血管疾病 综合症和中风。 VTE 的一线治疗方法是血液稀释剂；然而，这些代理是暂时的 对于许多高危 VTE 患者来说是禁忌的，例如那些遭受重大创伤和接受过治疗的患者 复杂的手术，出血是他们所关心的问题。下腔静脉 (IVC) 过滤器如图所示 人口。大多数 IVC 过滤器 (70%) 旨在在指定使用后收回；然而，只有 19%—— 30%被删除。不幸的是，如果不移除下腔静脉过滤器，并发症就会增加，这可能会非常严重。 费用昂贵（滤器回收费用为 3,000-12,000 美元，并发症治疗费用约为 67,000 美元）。因此，可吸收 开发了 IVC 过滤器，可在所需的持续时间内提供关键保护，然后简单地 从体内消失，从而减轻昂贵的切除手术和下游并发症。然而， 可吸收 IVC 过滤系统的一个重要限制是严重的凝块负担。监测吸收 使用成像技术的时间和任何显着的血栓负担将大大提高深部治疗的功效 静脉血栓治疗。 在这项研究中，我们将开发不透射线的可吸收过滤器，可以对其进行常规成像以提供 评估过滤器完整性的更便宜的替代方案。此外，双能过滤器的可视化 计算机断层扫描 (DECT) 将有助于区分两种或多种材料，例如 纳米颗粒 (NP)、碘和钙沉积物，可以提供更好的图像质量和定量 过滤器中存在的材料。具体来说，我们建议加入纳米颗粒（由金、铋、 镱、钽、钨、钡和锆），转化为临床可用的可吸收聚二氧环己酮 (PPDO) 缝合线，研究 PPDO 缝合线内 NP 输注对机械强度的影响， 经受人体生理作用后 10 周内的毒性和理化性质 条件，并使用优化的 DECT 参数进行大型动物成像研究，以确定 射线不透性、毒性和机械强度，以及图像增强缝合过程中的不良反应 尸检。我们还将开发一种 DECT 数学算法，用于量化不同的高 注入 PPDO 内的原子 (Z) 数对比材料。 我们的长期目标是开发一种完全可吸收的 IVC 过滤器，部署和监控成本低廉 通过常规成像方法，在建议的预防期内预防肺栓塞 然后就在没有干预的情况下消失了。这里概述的实验对于证明 使用 NP 作为嵌入该医疗设备中的 DECT 成像不透射线材料的可行性。 IVC 滤光片成像增强剂的成功开发也可能导致可吸收滤光片的广泛使用 其他心血管和骨科应用中的设备，其中固定装置（例如板、螺钉、钉子和 仅临时需要。