In Vivo Molding of Airway Stents Optimized to Preserve Ciliary Function for Neonates and Infants

优化气道支架体内成型以保护新生儿和婴儿的纤毛功能

• 批准号: 9317819
• 负责人: Pierre E Dupont
• 金额: $ 25.4万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-13 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9317819
• 关键词: Address; Adult; Air; Anatomy; Blood Vessels; Caliber; Cardiovascular system; Catheters; Child; Chronic; Complex; Computer Simulation; Congenital Abnormality; Custom; Devices; Distress; Ensure; Environmental air flow; Evaluation; Excision; FDA approved; Family suidae; Foreign-Body Reaction; Gases; Geometry; Goals; Granulation Tissue; Growth; Human; Impairment; Infant; Infection; Length; Liquid substance; Mammals; Metals; Modeling; Molds; Monitor; Motion; Mucous body substance; Operative Surgical Procedures; Patients; Pattern; Pediatrics; Pneumonia; Polymers; Population; Positioning Attribute; Procedures; Process; Reporting; Respiratory distress; Risk; Shapes; Silicones; Solid; Splint Device; Stents; Stream; Structure; Suction; System; Target Populations; Techniques; Technology; Testing; Thick; Tracheitis; Tracheobronchomalacia; Tube; Ultraviolet Rays; Validation; Variant; Ventilator; Work; alpha helix; base; cartilaginous; cost; design; endotracheal; experience; experimental study; expiration; flexibility; in vivo; innovation; man; migration; neonate; optical fiber; pressure; prevent; prototype; respiratory examination; treatment duration; two-dimensional

Project Summary Tracheobronchomalacia is the most common congenital defect of the central airways and has been identified in up to 15% of infants and 30% of young children undergoing bronchoscopic examination for respiratory distress. Intrinsic weakness of the airway leads to collapse during expiration resulting in air trapping and poor gas exchange. These neonates and infants are typically treated with positive pressure ventilation where the positive pressure acts as a pneumatic stent. During the 3-9 month treatment period, the child remains connected to the ventilator and close monitoring is required to provide regular suctioning of the endotracheal tube. Even with suctioning, the inability to clear mucus increases the risk of airway infections, e.g., pneumonia. Alternatively, stents can be used to prevent airway collapse, however, existing airway stents are sized for adults. While some neonates have been treated with metal mesh vascular stents, these stents induce the growth of granulation tissue through the mesh requiring a very invasive removal procedure. To avoid this issue, solid silicone tubes have been developed for adults, but they too have shortcomings. They block mucociliary function over the length of the stent resulting in mucous plugging and inspissated secretions that impede gas exchange. They also have a high migration rate. The goal of this project is to create a stent technology for neonates and infants that avoids the risks and costs of positive pressure ventilation while providing five innovations. First, stent geometry will minimize impairment of the mucociliary function by providing an unobstructed path along the stent length following observed mucus streaming patterns. Second, stent design will also facilitate atraumatic removal. Third, reduction of stent migration will be addressed through design of the contact geometry between the stent and airway. Fourth, stent geometry will be optimized to minimize the amount of foreign material in contact with the airway while still providing support equivalent to ventilation. Fifth, an in vivo molding process will be developed that can quickly and inexpensively produce a customized stent inside a patient's airway. Personalized stents can be vital for neonates and infants given the variability in airway anatomy associated with tracheobronchomalacia and the impact of adjacent cardiovascular structures. Aim 1 addresses the first four innovations and will involve optimizing stent geometry and dimensions for two design concepts using analytical models as well as FEM. To provide for rapid evaluation, the optimized designs will be fabricated using standard techniques (silicone-coated NiTi) and tested through ex vivo and in vivo experiments in a porcine model. Aim 2 will develop the fifth innovation of in vivo molding of customized stents. The stent will be comprised of a flexible polymer shell filled with a liquid UV-curable polymer. It will be delivered over a balloon catheter that is inflated to press the stent against the airway wall. UV light will be transmitted through the balloon catheter to cure the liquid polymer to the shape of the airway. This technique will be developed for one of the optimized designs from Aim 1 and tested in ex vivo and in vivo experiments.

项目摘要 气管支气管软化症是中央气道最常见的先天性缺陷， 在接受支气管镜检查的15%婴儿和30%幼儿中， 痛苦呼吸道的固有弱点导致呼气期间塌陷，导致空气滞留和不良 气体交换这些新生儿和婴儿通常用正压通气治疗， 正压就像一个充气支架。在3-9个月的治疗期间， 连接到呼吸机，并需要密切监测，以提供定期的气管内抽吸 管材.即使有抽吸，无法清除粘液也会增加气道感染的风险，例如，肺炎 或者，支架可用于防止气道塌陷，然而，现有的气道支架的尺寸适于 成年人了虽然一些新生儿已经用金属网血管支架治疗，但这些支架诱导了新生儿的血管扩张。 肉芽组织通过网状物生长，需要非常侵入性的去除程序。为了避免这个问题， 已经为成人开发了固体硅树脂管，但是它们也有缺点。它们会阻塞粘膜纤毛 在支架的长度上起作用，导致粘液堵塞和阻塞的分泌物， 交易所他们的移民率也很高。这个项目的目标是创造一种支架技术， 新生儿和婴儿，避免了正压通气的风险和成本，同时提供五个 创新。首先，支架的几何形状将通过提供一个可调节的支架位置来最小化对粘膜纤毛功能的损害。 在观察到的粘液流动模式之后，沿着支架长度的无阻碍路径沿着。二、支架设计 也有助于无创移除第三，减少支架移位将通过设计来解决 支架和气道之间的接触几何形状。第四，将优化支架几何结构，以最大限度地减少 与气道接触的异物量，同时仍提供相当于通气的支持。第五、 将开发一种体内成型工艺， 在病人的呼吸道里考虑到新生儿和婴儿的变异性，个性化支架可能至关重要。 与气管支气管软化相关的气道解剖结构和相邻心血管结构的影响。 目标1解决了前四项创新，并将涉及优化支架几何形状和尺寸， 使用分析模型以及FEM的设计概念。为了提供快速评估， 将使用标准技术（硅树脂涂层NiTi）制造设计，并通过体外和体内试验进行测试 在猪模型中的体内实验。Aim 2将开发第五项创新，即定制化体内成型 支架。支架将由填充有液体UV固化聚合物的柔性聚合物外壳组成。将 通过球囊导管递送，球囊导管膨胀以将支架压靠在气道壁上。紫外线将 通过球囊导管传输以将液体聚合物固化成气道的形状。这种技术 将针对目标1的优化设计之一开发，并在体外和体内实验中进行测试。