Removable airway stents that preserve mucociliary function

保留粘膜纤毛功能的可拆卸气道支架

基本信息

批准号：
10258203
负责人：
Pierre E Dupont
金额：
$ 30.38万
依托单位：
DOWN FROM THE DOOR, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10258203
关键词：
Address Adoption Adult Air Airway Disease Animal Experiments Animal Model Animals Asthma Boston Breathing Bronchoscopy Caliber Cannulas Cartilage Choking Chronic Chronic Bronchitis Clinical Complex Complication Continuous Positive Airway Pressure Coughing Dimensions Distal Dyspnea Engineering Environment Epithelial Evaluation Excision Exhalation Fibrosis Foreign Bodies Gases Goals Gold Granulation Tissue Growth Hemoptysis Histological Techniques Hour Human Inflammatory Response Lead Legal patent Length Maps Membrane Metals Modeling Monitor Motion Mucous body substance Operative Surgical Procedures Patients Pediatric Hospitals Performance Positioning Attribute Preclinical Testing Procedures Process Pulmonary Emphysema Rare Diseases Reconstructive Surgical Procedures Regulatory Pathway Research Respiratory Signs and Symptoms Respiratory Tract Infections Risk Safety Shapes Sheep Silicones Solid Stents Surgeon Symptoms System Technology Testing Thick Time Tissues Trachea Tracheobronchomalacia Trauma Tube alternative treatment clinically relevant cost design efficacy evaluation efficacy testing engineering design experimental study implantation in vivo innovation meetings migration mucus clearance muscle degeneration novel novel strategies preservation pressure prevent prototype research clinical testing respiratory examination respiratory periodicity response safety study safety testing side effect tool ventilation verification and validation

Address Adoption Adult Air Airway Disease Animal Experiments Animal Model Animals Asthma Boston Breathing Bronchoscopy Caliber Cannulas Cartilage Choking Chronic Chronic Bronchitis Clinical Complex Complication Continuous Positive Airway Pressure Coughing Dimensions Distal Dyspnea Engineering Environment Epithelial Evaluation Excision Exhalation Fibrosis Foreign Bodies Gases Goals Gold Granulation Tissue Growth Hemoptysis Histological Techniques Hour Human Inflammatory Response Lead Legal patent Length Maps Membrane Metals Modeling Monitor Motion Mucous body substance Operative Surgical Procedures Patients Pediatric Hospitals Performance Positioning Attribute Preclinical Testing Procedures Process Pulmonary Emphysema Rare Diseases Reconstructive Surgical Procedures Regulatory Pathway Research Respiratory Signs and Symptoms Respiratory Tract Infections Risk Safety Shapes Sheep Silicones Solid Stents Surgeon Symptoms System Technology Testing Thick Time Tissues Trachea Tracheobronchomalacia Trauma Tube alternative treatment clinically relevant cost design efficacy evaluation efficacy testing engineering design experimental study implantation in vivo innovation meetings migration mucus clearance muscle degeneration novel novel strategies preservation pressure prevent prototype research clinical testing respiratory examination respiratory periodicity response safety study safety testing side effect tool ventilation verification and validation

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项目摘要

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.

项目摘要在多达13％的成年患者中观察到气管异脑瘤虽然是一种罕见疾病支气管镜检查呼吸道症状和多达23％的慢性支气管炎患者。固有的软骨和/或纤维肌膜的弱点会导致空气捕获和较差天然气交换。症状包括呼吸困难，情节性窒息，慢性咳嗽和周期性呼吸感染。虽然可以使用连续的正气道压力（CPAP）来防止崩溃，但很难每天24小时使用CPAP，每天进行每天的活动。许多手术程序已经开发以加强气道并因此防止崩溃，但是这些涉及大手术，并且具有高度并发症率。或者，虽然可以使用支架来防止气道崩溃，但现有的气道支架是无效。金属网格支架通过网格诱导肉芽组织的生长，需要非常侵入性删除过程。为了避免这种情况，已经开发了固体硅管，但它们也有缺点。它们沿着航空公司轻松迁移，并在支架长度上阻断粘膜钙金功能，从而粘液塞。可度假的支架旨在克服去除的挑战，但支架碎片化在分辨率期间可以阻止远端气道。为了满足这一临床需求，波士顿儿童医院（BCH）由外科医生，肺科医生和工程师组成的团队创建了一种螺旋支架技术并进行了测试它使用体内动物实验。这些支架允许粘膜刷流，其螺钉状形状可防止它们迁移一旦位于气道。即使使用一种新型的支气管镜工具上皮化，该工具会撤离运动，以使支架从支架上撤回组织并进入套管以去除。 BCH团队已与DFD解决方案联手商业化这项技术。作为迈向510（k）应用程序的第一步，该项目提出了两个具体目标。在第一个目的，我们将评估乳酸动物模型中支架系统的效率和安全性与成年人气管的尺寸。这些12周的实验将有足够的持续时间来启用在临床相关时间段内评估支架性能。支气管镜将用于评估气道通畅，颗粒组织的形成，粘液间隙，支架迁移和支架易于消除。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。 AIM 2将通过定义关键来设计用于临床使用的支架和工具可以在现有临床工作流程中使用的要求和功能。这将包括进行人类因子研究以获取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验证测试计划。 AIM 2的结论将成为FDA预提前提取的，以获取适当的监管途径的澄清并需要的临床前途径和临床测试以支持市场前的清理或批准。