In Vitro and In Vivo Characterization of Tunable Fibrous Scaffolds for Tracheal Tissue Engineering

Abstract

Laryngotracheal disorders resulting in airway obstruction, although rare, can cause significant morbidity and can be life threatening. Current treatments include augmenting the airway with the patient's own rib cartilage. Specialized surgical technique and an invasive, multi-site surgery are required for this procedure. Thus, an off-the-shelf tissue-engineered product is needed that would replace the need for autologous tissue and eliminate the challenges for the surgeon and patient. The tissue-engineering approach of "scaffold, cells, signals" was used to design a fibrous, graded bilayer scaffold with one layer providing long-term structural support (i.e., polycaprolactone (PCL)) and the other layer allowing for short-term tissue ingrowth and drug delivery (i.e., poly(lactic-co-glycolic) acid (PLGA)). In vitro degradation and several in vivo studies were completed to evaluate the scaffold performance and refine the design. Incorporating 3-D printed polymeric rings into the fibrous scaffold enhanced mechanical performance and growth factors and cells improved cellular response and tissue ingrowth. Additionally, research techniques were refined to analyze outcomes of these experiments, including microCT and stenosis quantification. The application of electrospun materials to tracheal defect repair was taken from idea to preclinical practice in this thesis and has established a platform for further research and development, with the potential for translation to clinical use.