MagSToNE - a magnetic system for kidney stone fragment elimination

项目摘要 尿（肾）结石疾病是常见的，在美国每11人中就有1人患病，费用超过2美元。 在美国，每年的医疗保健支出高达10亿美元。泌尿外科内镜治疗现状 结石病的中心是输尿管镜激光碎石术，将结石粉碎成更小的部分。的 碎片或者用金属丝篮一个接一个地主动从体内取出，或者让其自发地通过。 根据石头碎片的大小，该过程可能是低效的、乏味的和耗时的。 手术室很贵。使患者无结石是防止进一步 由于残余结石碎片导致的并发症或重复干预，但目前的结石清除率仅接近 60- 75%长期目标是通过在较短时间内实现较高的结石清除率来改善临床结局。 时间量。该R21应用的目的是开发、表征和测试一种新型的 基于磁性的技术，以改善肾结石碎片检索。 我们提出了MagSToNE（磁性系统的总肾结石消除），一种新的方法， 磁性纳米技术用于有效的结石碎片回收。MagSToNE由一根柔性磁线组成， 具有生物相容性塑料护套，和超顺磁性颗粒，其被功能化以结合到肾脏 石头磁导丝与标准输尿管镜兼容，尺寸与导丝相似 通常用于输尿管镜检查。它还被独特地设计为产生更强的磁场 梯度比典型的磁铁。在肾结石的激光破碎之后，结石碎片被涂覆有 磁性纳米颗粒已经被功能化以结合肾结石。这些石头可以很容易地 通过磁线回收包裹，与传统的碎石机相比， 传统的铁丝篮。 该技术将通过以下具体目标进行开发：（1）开发和优化 超顺磁性颗粒和磁性线捕获和取回结石碎片;和（2）比较 MagSToNE与传统取石方法相比的性能，具有体内可行性， 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清除到利用吸引磁力的清除， 承诺更好的性能。拟议的研究是重要的，因为它有可能大大 改善临床结果并降低与肾结石手术相关的医疗费用。

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.