Nanoparticle-Infused Radiopaque Absorbable Medical Device

 描述(申请人提供)：静脉血栓栓塞症(VTE)是仅次于急性冠脉综合征和中风的第三大常见心血管疾病。VTE的一线治疗是血液稀释剂；然而，对于许多高危VTE患者来说，这些药物暂时是禁忌，例如那些有重大创伤的患者和那些接受复杂手术的患者，他们担心出血。下腔静脉滤器(IVC)在这一人群中使用。大多数IVC过滤器(70%)打算在指示使用后回收；然而，只有19%-30%被移除。不幸的是，当不取出下腔静脉滤器时，并发症就会增加，这可能是非常昂贵的(取回滤器的费用为3-12000美元，治疗并发症的费用约为67K美元)。因此，开发了可吸收的下腔静脉滤器，这种滤器在其所需的持续时间内提供关键的保护，然后简单地从体内消失，从而减轻昂贵的取出程序和下游并发症。然而，可吸收下腔静脉滤器系统的一个重要限制是显著的血块负荷。使用影像技术监测深静脉血栓的吸收时间和任何明显的血栓负荷将极大地提高深静脉血栓的治疗效果。在这项研究中，我们将开发不透射线的可吸收滤光片，这种滤光片可以常规成像，为评估滤光片的完整性提供一种更便宜的替代方案。此外，在双能量计算机断层扫描(DECT)下对过滤器进行可视化将有助于区分两种或两种以上的材料，例如纳米颗粒(由金、铋、Yb或钽制成)、碘和钙沉积物，这可以提供更好的图像质量和对过滤器中存在的材料进行量化。 具体地说，我们提出了以下目标：目的1.测定注入纳米颗粒的PPDO缝合线的放射不透明度、机械强度和结晶度，并量化在人体生理条件下10周内注入和释放的纳米颗粒(由金、铋、Yb和Ta组成)的量。目的2.探讨DECT鉴别各种不透射线材料与血栓的能力，并优化DECT成像不透射线PDDO滤光片的参数。目的3：在猪的动物模型中，测定植入纳米颗粒的PPDO缝线的放射不透明度和机械强度，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下腔静脉滤器，以低廉的成本部署并通过传统成像方法进行监测，在推荐的预防性期间防止肺栓塞，然后在不干预的情况下干脆消失。这里概述的实验对于证明使用纳米粒子作为嵌入该医疗设备内的DECT成像的不透射线材料的可行性至关重要。下腔静脉滤器成像增强剂的成功开发也可能导致可吸收装置在其他心血管和骨科应用中的广泛使用，在这些应用中，固定装置(例如板、螺丝、钉子和棒)只是临时需要的。

 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.