MagSToNE - a magnetic system for kidney stone fragment elimination

项目摘要 尿路(肾结石)疾病很常见，在美国大约每11人中就有1人受到影响，花费2美元。 美国每年的医疗支出为10亿美元。泌尿系疾病的内窥镜手术治疗现状 结石病以输尿管镜下激光碎石术为中心，将结石分成更小的部分。这个 碎片要么用钢丝篮一个接一个地从身体上主动取回，要么让它自发通过。 根据石块的大小，该过程可能效率低下、繁琐且耗时 这间手术室很贵。让病人排出结石是防止进一步 残余结石碎片引起的并发症或重复干预，但目前的结石排净率仅接近 60%-75%。长期目标是通过在较短的时间内获得更高的结石排净率来改善临床结果。 时间长短。此R21应用程序的目标是开发、表征和测试一种新的 基于磁性的技术提高了肾结石碎片的检索能力。 我们提出了一种新的方法MagSToNE(MagstoNE)，该方法基于 磁性纳米技术可有效恢复石块碎片。MagSToNE由一根柔软的磁线组成 具有生物相容的塑料鞘和超顺磁性颗粒，这些颗粒被功能化以结合到肾脏上 石头。磁丝与标准输尿管镜兼容，尺寸与导丝相似 常规用于输尿管镜检查。此外，它还经过独特的设计，可以产生更强的磁场 比典型的磁铁更容易产生渐变。在肾结石激光碎石后，结石碎片上涂有 磁性纳米颗粒已经被功能化，可以结合到肾结石上。然后这些石头就可以很容易地 通过磁线集体回收，相比于磁线，提高了清除石头的效率 传统的钢丝篮。 这项技术将通过以下具体目标进行开发：(1)开发和优化 超顺磁性粒子和磁丝，以捕获和取回石块；以及(2)比较 MagSToNE与传统取石方法相比的性能，具有体内可行性和 猪模型中的生物分布/毒性研究。这个项目是创新的，因为它改变了石头的范式 从纯粹基于机械回收的间隙到利用吸引力和磁力的间隙 承诺会有更好的表现。这项拟议的研究意义重大，因为它有可能大幅提高 改善临床结果，降低与肾结石手术相关的医疗成本。

Project Summary Urinary (kidney) stone disease is common and affects about 1 in 11 people in the United States, costing > $2 billion in healthcare expenditures per year in the United States. Current endoscopic surgical treatment of urinary stone disease is centered around ureteroscopic laser lithotripsy to fragment the stone into smaller parts. The fragments are either actively retrieved from the body one by one with a wire basket or left to pass spontaneously. Depending on the size of the stone fragments, the process can be inefficient, tedious, and time-consuming in the operating room which is expensive. Rendering a patient stone-free is the best way to prevent further complications or repeat interventions due to residual stone fragments, yet current stone-free rates only approach 60-75%. The long-term goal is to improve clinical outcomes by achieving higher stone-free rates in a shorter amount of time. The objective of this R21 application is to develop, characterize, and test the feasibility of a novel magnetic-based technology to improve kidney stone fragment retrieval. We propose MagSToNE (Magnetic System for Total Nephrolith Elimination), a new approach based on magnetic nanotechnology for efficient stone fragment retrieval. MagSToNE consists of a flexible magnetic wire with a biocompatible plastic sheath, and superparamagnetic particles which are functionalized to bind to kidney stones. The magnetic wire is compatible with standard ureteroscopes and is similar in size to the guidewires routinely used in ureteroscopy. It is additionally uniquely designed to generate much stronger magnetic field gradients than a typical magnet. After laser fragmentation of a kidney stone, stone fragments are coated with magnetic nanoparticles which have been functionalized to bind to kidney stones. The stones can then be easily retrieved en masse by the magnetic wire, improving the efficiency of stone clearance compared to the conventional wire basket. This technology will be developed through the following specific aims: (1) to develop and optimize the superparamagnetic particles and magnetic wire to capture and retrieve stone fragments; and (2) to compare the performance of MagSToNE to conventional stone retrieval methods, with in vivo feasibility and biodistribution/toxicity studies in a porcine model. This project is innovative in that it shifts the paradigm of stone clearance from one based purely on mechanical retrieval to one that utilizes attractive magnetic forces and promises better performance. The proposed research is significant because it has the potential to substantially improve clinical outcomes and reduce healthcare costs related to kidney stone surgery.