Nanoparticle-Infused Radiopaque Absorbable Medical Device

 描述（由申请人提供）：静脉血栓栓塞（VTE）是继急性冠状动脉综合征和卒中之后的第三大常见心血管疾病。静脉血栓栓塞的第一线治疗是血液稀释剂;然而，这些药物暂时禁忌用于许多有风险的静脉血栓栓塞患者，例如患有严重创伤和接受复杂手术的患者，对他们来说，出血是一个问题。下腔静脉（IVC）滤器适用于该人群。大多数IVC滤器（70%）预期在其适应症使用后回收;然而，仅19-30%被移除。不幸的是，当IVC过滤器未被移除时，并发症会增加，这可能非常昂贵（过滤器回收费用为3 - 12 K美元，并发症治疗费用约为67 K美元）。因此，开发了可再吸收的IVC过滤器，其在其所需的持续时间内提供关键保护，然后简单地从体内消失，从而减轻了昂贵的移除程序和下游并发症。然而，可吸收IVC过滤器系统的一个重要限制是显著的凝块负荷。使用成像技术监测吸收时间和任何显著的凝块负荷将大大提高深静脉血栓形成治疗的疗效。 在本研究中，我们将开发可常规成像的不透射线可吸收滤器，以提供评估滤器完整性的更便宜的替代方案。此外，在双能量计算机断层扫描（DECT）下的过滤器可视化将有助于区分两种或多种材料，例如纳米颗粒（由金、铋、镱或钽制成）、碘和钙沉积物，这可以提供更好的图像质量和过滤器中存在的材料的量化。 具体而言，我们提出以下目标：目标1。确定纳米粒子注入PPDO缝线的不透射线性、机械强度和结晶度，并量化在人体生理条件下10周内注入和释放在PPDO缝线内的纳米粒子（由金、铋、镱和钽组成）的量。 目标2.研究DECT区分各种不透射线材料与血栓的能力，并优化使用DECT进行不透射线PDDO滤器成像的参数。 目标3：在猪动物模型中确定纳米颗粒注入PPDO缝线的不透射线性和机械强度，并确定尸检后缝线的不良反应。 我们的长期目标是开发一种完全可吸收的IVC过滤器，以廉价的方式部署并通过传统成像方法进行监测，可以在推荐的预防期内预防肺栓塞，然后在无需干预的情况下直接消失。这里概述的实验对于证明使用纳米颗粒作为嵌入该医疗器械的DECT成像的不透射线材料的可行性至关重要。IVC过滤器成像增强剂的成功开发也可能导致可吸收器械在其他心血管和骨科应用中的广泛使用，其中仅临时需要固定装置（如板、螺钉、髓内钉和棒）。

 DESCRIPTION (provided by applicant): 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 ($3-12K for filter retrieval and ~$67K 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 radiopaque absorbable filters that can be routinely imaged to offer a less expensive alternative for 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 (made of gold, bismuth, ytterbium, or tantalum), iodine, and calcium deposits, which could provide better image quality and quantification of the materials present in the filter. Specifically, we propose the following aims: Aim 1. Determine the radiopacity, mechanical strength, and crystallinity of nanoparticle-infused PPDO sutures and quantify the amount of nanoparticles (composed of gold, bismuth, ytterbium, and tantalum) infused and released within PPDO sutures in human physiological conditions over a period of 10 weeks. Aim 2. Investigate the ability of DECT to differentiate various radiopaque materials from thrombus and to optimize the parameters for imaging radiopaque PDDO filters using DECT. Aim 3: Determine in swine animal model the radiopacity and mechanical strength of nanoparticle-infused PPDO sutures and identify adverse reactions to the sutures after necropsies. 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 nanoparticles 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.