Removable airway stents that preserve mucociliary function

项目摘要 气管支气管软化症虽然是一种罕见的疾病，但在13%的成年患者中观察到， 支气管镜检查有呼吸道症状的慢性支气管炎患者高达23%。内在 软骨和/或纤维肌膜的薄弱导致塌陷， 气体交换症状包括呼吸困难，发作性窒息，慢性咳嗽和周期性呼吸困难。 感染.虽然持续气道正压通气（CPAP）可用于防止萎陷，但难以 每天24小时使用CPAP进行日常活动。许多外科手术已经被 发展，以加强气道，从而防止崩溃，但这些涉及大手术，并有很高的 并发症发生率。或者，虽然支架可用于防止气道塌陷，但现有的气道支架 无效。金属网状支架通过网状物诱导肉芽组织生长，需要非常侵入性的植入。 移除程序。为了避免这种情况，已经开发了固体硅胶管，但它们也有缺点。 它们很容易沿着气道迁移，并在支架的长度上阻塞粘膜纤毛功能，导致 粘液堵塞可吸收支架旨在克服取出的挑战，但支架碎裂 会阻塞远端气道。为了满足这一临床需求，波士顿儿童医院（BCH） 一个由外科医生、肺病学家和工程师组成的研究小组创造了一种螺旋支架技术， 使用体内动物实验。这些支架允许粘膜纤毛流动，而它们的螺旋状形状阻止它们流动。 一旦进入呼吸道就会迁移它们也可以在最小的损伤下被移除， 使用一种新型的支气管镜工具进行上皮化， 组织并进入套管中以便移除。BCH团队与DFD Solutions联手， 这个技术。作为510（k）申请的第一步，该项目提出了两个具体目标。上 目的是，我们将评估我们的支架系统在匹配的软化动物模型中的有效性和安全性。 成人气管的尺寸。这些为期12周的实验将有足够的时间， 在临床相关时间段内评价支架性能。支气管镜检查将用于评估 气道通畅、肉芽组织形成、粘液清除、支架移位及支架难易程度 的拔除.我们还将采用组织学技术来评估组织损伤、肉芽组织、纤维化和 炎症反应。目标2将重点关注通过定义关键参数来设计用于临床的支架和工具。 这些要求和功能将能够在现有临床工作流程中使用。这将包括进行 人为因素研究，以获得系统的程序和过程图，以及工程设计， 定义用户/技术要求以及验证和确认测试计划。目标2的结论将 作为FDA预提交文件，以获得关于适当监管途径和所需临床前 和临床试验，以支持上市前许可或批准。

PROJECT SUMMARY Tracheobronchomalacia, while a rare disease, is observed in up to 13% of adult patients who undergo bronchoscopic examination for respiratory symptoms and up to 23% of patients with chronic bronchitis. Intrinsic weakness of the cartilage and/or fibromuscular membrane leads to collapse resulting in air trapping and poor gas exchange. Symptoms include labored breathing, episodic choking, chronic cough and periodic respiratory infections. While continuous positive airway pressure (CPAP) can be used to prevent collapse, it is difficult to perform everyday activities while using CPAP 24 hours a day. A number of surgical procedures have been developed to reinforce the airways and so prevent collapse, but these involve major surgery and have high complication rates. Alternatively, while stents can be used to prevent airway collapse, existing airway stents are ineffective. Metal mesh stents induce the growth of granulation tissue through the mesh requiring a very invasive removal procedure. To avoid this, solid silicone tubes have been developed, but they too have shortcomings. They migrate easily along the airways and block mucociliary function over the length of the stent resulting in mucous plugging. Resorbable stents are intended to overcome the challenge of removal, but stent fragmentation during resorption can block distal airways. To address this clinical need, a Boston Children’s Hospital (BCH) team, comprised of surgeons, pulmonologists and engineers, has created a helical stent technology and tested it using in vivo animal experiments. These stents allow mucociliary flow and their screw-like shape prevents them from migrating once positioned in the airways. They can also be removed with minimal damage even if epithelialized using a novel bronchoscopic tool that employs an unscrewing motion to retract the stent from the tissue and into a cannula for removal. The BCH team has joined forces with DFD Solutions to commercialize this technology. As an initial step toward a 510(k) application, this project proposes two Specific Aims. In the first aim, we will evaluate the efficacy and safety of our stent system in a malacic animal model matched the dimensions of an adult human trachea. These 12-week experiments will be of sufficient duration to enable evaluation of stent performance over a clinically relevant time period. Bronchoscopy will be used to evaluate airway patency, the formation of granulation tissue, mucus clearance, stent migration and the ease of stent removal. We will also employ histological techniques to assess tissue damage, granulation tissue, fibrosis and inflammatory response. Aim 2 will focus on designing the stent and tools for clinical use by defining the critical requirements and features that will enable use within existing clinical workflows. This will include conducting human-factors research to obtain procedural and process maps for the system as well as engineering design to define user / technical requirements and verification and validation testing plans. The conclusion of Aim 2 will be an FDA pre-submission to obtain clarification on the appropriate regulatory pathway and required preclinical and clinical testing to support pre-market clearance or approval.