Removable airway stents that preserve mucociliary function

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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.