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

项目摘要 气管、支气管软化症是中央呼吸道最常见的先天缺陷，已被确诊。 多达15%的婴儿和30%的幼儿接受支气管镜检查以检查呼吸道 苦恼。呼吸道固有的虚弱会导致呼气时的塌陷，从而导致空气滞留和不良 气体交换。这些新生儿和婴儿通常采用正压通气治疗，其中 正压起到充气支架的作用。在3-9个月的治疗期间，孩子仍然 连接到呼吸机，并需要密切监测以提供常规的气管内吸气 管子。即使进行吸痰，无法清除粘液也会增加呼吸道感染的风险，例如肺炎。 或者，支架可以用来防止呼吸道塌陷，然而，现有的气道支架的大小是为了 成年人。虽然一些新生儿接受了金属网状血管支架治疗，但这些支架导致 肉芽组织通过网眼的生长需要非常侵入性的去除程序。为避免此问题， 实心硅胶管是为成年人开发的，但它们也有缺点。它们会阻塞粘液纤毛 在支架长度上起作用，导致粘液堵塞和分泌物浓缩，从而阻碍气体 交换。他们也有很高的迁移率。该项目的目标是创造一种支架技术，用于 避免风险和成本的新生儿和婴儿，同时提供5个 创新。首先，支架的几何形状将通过提供一种 沿支架长度的通畅路径遵循观察到的粘液流动模式。第二，支架设计 也将有助于无损伤的移除。第三，减少支架移位将通过设计 支架和呼吸道之间的接触几何形状。第四，支架的几何形状将被优化，以最大限度地减少 与呼吸道接触的异物的量，同时仍提供相当于通风的支持。第五, 将开发一种体内成型工艺，可以快速且廉价地生产定制的支架 在病人的呼吸道内。个性化支架对于新生儿和婴儿来说是至关重要的，因为 与气管、支气管软化症相关的呼吸道解剖及其对邻近心血管结构的影响。 目标1解决了前四项创新，并将涉及优化支架的几何形状和尺寸 使用分析模型和有限元方法的设计概念。为了提供快速评估，优化的 设计将使用标准技术(硅胶涂层NiTi)制造，并通过体外和体内测试 在猪模型上进行活体实验。Aim 2将开发定制的体内成型的第五次创新 支架。支架将由一个填充了液态紫外光固化聚合物的柔性聚合物外壳组成。会是 通过充气的气囊导管将支架压在气道壁上。紫外光将是 通过气囊导管将液体聚合物固化成呼吸道形状。这项技术 将针对目标1中的优化设计之一进行开发，并在体外和体内实验中进行测试。

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.