Nanoparticle- Infused Radiopaque Absorbable Medical Device

项目总结 静脉血栓栓塞症(VTE)是仅次于急性冠状动脉病变的第三大常见心血管疾病 综合症和中风。静脉血栓栓塞症的一线治疗是血液稀释剂；然而，这些药物只是暂时的 禁忌用于许多高危VTE患者，如那些有严重创伤的患者和那些 复杂的手术，出血是一个令人担忧的问题。下腔静脉滤器(下腔静脉滤器)在图中显示。 人口。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，当不移除下腔静脉滤器时，并发症会增加，这可能会非常 费用昂贵(3,000-12,000美元用于滤器检索，约67,000美元用于治疗并发症)。因此，可再吸收 开发了IVC过滤器，它在所需的持续时间内提供关键保护，然后只需 从体内消失，从而减轻昂贵的移除程序和下游并发症。然而， 可吸收下腔静脉滤器系统的一个重要限制是严重的血块负荷。监测吸收情况 使用成像技术的时间和任何明显的血栓负担都将极大地提高深部手术的疗效 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滤光片，这种滤光片可以常规成像以提供 评估过滤器完整性的更便宜的替代方案。此外，双能量下的滤光片的可视化 计算机断层扫描(DECT)将有助于区分两种或两种以上材料，例如 纳米颗粒(NPs)、碘和钙沉积，可以提供更好的图像质量和量化 过滤器中存在的材质。具体地说，我们建议将NPs(由金、铋、 Yb2+、Tt2+、W3+、W3+、Nb2+、Tb2+、W3+、W3+、Ba2+和Z2+)，转化为临床上可吸收的聚二氧六环 (PPDO)缝合，观察PPDO缝线内注入NP对机械强度的影响， 在人体生理条件下10周内的毒性和物理化学性质 条件，并使用优化的DECT参数执行大型动物成像研究以确定 放射不透明度、毒性和机械强度，以及影像增强缝合的不良反应 尸检。我们还将为DECT开发一个数学算法，用于量化不同的高压 在PPDO内注入原子(Z)数对比剂。 我们的长期目标是开发一种完全可吸收的IVC过滤器，以低廉的成本部署和监控 通过传统的成像方法在推荐的预防性期间预防肺栓塞 然后干脆就消失了，没有任何干预。这里概述的实验将对演示 将纳米粒子用作植入该医疗设备内的DECT成像的不透射线材料的可行性。 下腔静脉滤过器成像增强剂的成功开发也可能导致可吸收材料的广泛使用 其他心血管和骨科应用中的装置，其中固定装置(如钢板、螺丝、钉子和 燃料棒)仅在临时基础上需要。

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.