Tracheobonchomalacia (TBM) is a congenital or acquired deficiency of tracheal and/or bronchial cartilages that presents with dynamic airway collapse, respiratory difficulties, and, in severe cases, acute life-threatening events. TBM prevalence is estimated at 1 in 2,200 children1, and severe cases can result in death or require tracheostomy with ventilation for 2-3 years, a significant burden on the child and family2,3. We recently developed a bioresorbable, patient specific 3D printed polycaprolactone (PCL) splint to treat TBM, reporting the first case in the New England J. of Medicine4. Three subsequent children with life threatening TBM were saved with the splint and the first child continues to be asymptomatic 30 months post-surgery. However, long term clinical application of the splint requires further engineering to reduce the risk of fatigue failure in addition to understanding how resorption of the splint affects mechanical deformation and remodeling of the airway to improve safety and efficacy of the splint. In addition, the FDA also requires such data for regulatory approval based on our August 22, 2014 meeting with the FDA to initiate a phase I clinical trial for Humanitarian Device Exempt (HDE) approval. We will address these questions in two specific aims using both in vitro and in vivo preclinical model, the Yorkshire pig.
The first aim will characterize splint degradation both in vitro and in vivo for up to 2 years.
The second aim will use this data to characterize how the splint affects airway mechanics.
Tracheobronchomalacia (TBM) is a congenital or acquired deficiency of tracheal and/or bronchal structures resulting in partial or complete collapse of tracheal and/or bronchal segments. TBM presents with dynamic airway collapse and respiratory difficulties. In severe cases, TBM results in acute life-threatening events and even death. We have developed a bioresorbable splint for TBM that can be custom designed for patient specific anatomy and custom designed to have specific mechanical properties. The splint is fabricated using a 3D printing process which we have developed for bioresorbable PCL. To improve safety and efficacy of the splint, it is critical to investigate design and 3D printing fabrication effects on the long-term fatigue and degradation of the splint. In addition, the FDA also saw a need for more preclinical data on long term splint degradation and how this degradation affects splint and airway mechanics. We are currently going forward with plans to perform a clinical trial on the splint. We will evaluate degradation both in vitro and in a large in vivo preclinical model, the Yorkshire Pig. We will further perform finite element modeling of malacic airways with the splint to determine how degradation affects mechanical stimulation of the airway. This data is critical to move ahead with the first clinical trial for a 3D printed bioresorbable device in the United States.
| Hollister, Scott J; Hollister, Maximilian P; Hollister, Sebastian K (2017) Computational modeling of airway instability and collapse in tracheomalacia. Respir Res 18:62 |
