Ex vivo and In vivo Model Advancements for Airway Stent Design Optimization - PROJECT SUMMARY Tracheobronchomalacia is a rare disease involving excessive airway collapse due to weakening of the airway walls. It is diagnosed in 13% of adults and 30% of children who undergo bronchoscopy for respiratory distress. The disease is characterized by the percentage collapse and collapse-morphology in the weakened airway segment. The collapse-morphology can vary depending on the relative anatomical region(s) of tissue weakening. Mild to moderate Tracheobronchomalacia can be treated non-invasively via positive pressure ventilation. Positive pressure ventilation, while noninvasive, requires the patient to be attached continuously to a pressure generating device for effective treatment. Severe Tracheobronchomalacia usually requires surgical intervention that involves attaching supportive materials outside the trachea that thwarts regional collapse. Surgical interventions are complex and require long post-operative recovery. Airway stents provide a simple, economical and minimally invasive treatment mode. Unfortunately, available stents are avoided or only implanted for monitored short periods due to stent-associated complications of excessive granulation tissue formation and mucus plugging resulting from the foreign body reaction against the implanted stent. Stent physical characteristics play a significant role in inducing excessive granulation tissue formation and mucostasis. The stent physical characteristics which include the stent material, geometry and size, need to be optimized at the design and development stage to minimize the physical impact during implantation. Existing benchtop and animal models can neither reliably generate the grades and morphologies of Tracheobronchomalacia, nor do they possess the granularity needed to perform design optimization. In this proposal we will establish new research tools and protocols that will substantially advance the stent design process and propel the development of viable airway stents. We present the first benchtop platform for rapid stent testing capable of generating specific grades and morphologies of Tracheobronchomalacia and accurately simulate dynamic airway collapse. Our system evaluates stent effectiveness in the clinically relevant parameter of airway lumen cross-sectional area. Furthermore, the platform can map the device-to-airway contact force distribution during dynamic airway collapse. In aim 1, we will first establish the protocols for reliably generating the clinical grades of Tracheobronchomalacia. Next, we will evaluate the performance of helical and axial stent designs of varying geometric feature values. This will determine the geometric parameter for each stent design for treating Tracheobronchomalacia using minimum material and contact forces. In aim 2, we will study the effect of stent geometry and oversizing on the spatial distribution and severity of granulation tissue formation and mucostasis. At the conclusion of experiments from both aims, we will attempt to establish a relationship between the spatial characteristics of granulation tissue recorded from the animal study and the benchtop contact forces. This will enable assessing stent designs prone to granulation tissue complications before testing stents in animals.
