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.
Airway collapse is a common cause of respiratory distress in very young children. The only FDA-approved treatment is to provide chronic positive airway pressure, but this approach carries risks, including pneumonia. While airway stents have been developed for adults, they are too large and they have shortcomings, e.g, they impede mucus transport and can be difficult to remove. To address this need, we propose to design airway stents for neonates and infants that avoid these problems. Furthermore, to accommodate the large variation in airway shape and size among the children who need these devices, we will develop a technology for inexpensively molding personalized stents inside the child's airways as the stent is being delivered.
