Advanced Bioreactors for Evaluation and Systematic Optimization of Decellularization and Recellularization of the Lung and Trachea

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Diseases affecting the airways are an important clinical problem and for the majority of**patients with end-stage disease, transplantation of lung and/or trachea has become the only**life-saving option. Ideally we need access to off-the-shelf replacement grafts reducing the**dependency on donor organs, wait-time and risk of death. In the lung, organ regeneration is**achieved by using biohybrid devices with partially synthetic or natural scaffolds. The approach**is to utilize advanced bioreactors operating under optimized physiological conditions to**repopulate with new cells, scaffolds in which the resident cells have been removed, and use**for functional replacement of damaged tissue. While transplantation of regenerated whole**lungs is a far-off goal, we exploit the simpler system of the trachea with which we have**extensive expertise while addressing key issues that will set the foundation for future clinical**application of whole lung grafts. At the end of the funding period, we expect to begin clinical**translation of a functional tracheal biograft used to address small airway and larger tracheal**defects, respectively. The optimized tracheal bioreactors developed can result in commercial**products via licensing to already existing lung biotech companies or through company**creation ventures with focus on enhanced organ-specific bioreactors. In addition, the**development of a computational model of fluid flow using a computerized geometrical models**of vascular (and airway) networks will allow in silico experimental programs to explore**strategies for targeted cell delivery. Models developed here have the potential for significant**impact in lung tissue engineering, and can be applied to research groups focused on other**organs. Completion of this work will set in motion a therapeutic strategy with the potential to**save lives and vastly improve the quality of life of Canadians suffering from end-stage lung**disease.