Development of 3D-Printed, Drug-Eluting Airway Stents for the Personalised and Local Treatment of Central Airway Pathologies

Abstract

Airway stents are the most widely used means of palliative treatment for patients suffering from central airway obstruction (CAO). CAO may occur directly from airway stenosis, respiratory cancers, or tracheobronchomalacia, a symptom of weakening airway cartilage. Current airway stents are constructed using medical-grade silicone or nickel-titanium (nitinol) alloy, that have fixed geometry and are inserted via bronchoscopic surgery. These stents have many shortcomings due to their standardised size and dimensions that are not compatible with the patient’s lung anatomy, causing stent migration, granulation tissue growth, and airway secretions. These incidences will lead to airway restenosis and will require further surgical intervention. In malignant central airway obstructions, patients encounter further morbidity with concomitant intravenous delivery of chemotherapeutics which result in significant systemic side-effect profile. The thesis addresses current shortcomings of improper stent fitting, prevention of granulation tissue formation and local therapy of respiratory cancer relapse, with the development of a controlled drug-eluting stent containing an anti-proliferative drug, paclitaxel. The thesis first evaluates the current state-of-the-art technologies used in the development of respiratory stents to identify knowledge gap withing the field (chapter 1). Subsequently, it evaluates the feasibility of incorporating paclitaxel drug particles into a silicone elastomer that will be used for airway stents and the corresponding drug release profiles from silicone elastomer (chapter 2). Then, alterations on various physicochemical properties of the drug particles and silicone formulations were made to modulate the release kinetics of paclitaxel from the silicone (chapter 3). The efficacy of released paclitaxel was investigated in its ability to control lung cancer (chapter 2) and granulation tissue growth (chapter 5). Finally, the thesis discusses two methods used to develop a more fitting airway stent: 1) using a novel 3D-printing platform in the creation of a surgical guide (chapter 4) and 2) development of a silicone casting platform that is personalisable to individual patient airway geometry (chapter 5).