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 ofpatients with end-stage disease, transplantation of lung and/or trachea has become the onlylife-saving option. Ideally we need access to off-the-shelf replacement grafts reducing thedependency on donor organs, wait-time and risk of death. In the lung, organ regeneration isachieved by using biohybrid devices with partially synthetic or natural scaffolds. The approachis to utilize advanced bioreactors operating under optimized physiological conditions torepopulate with new cells, scaffolds in which the resident cells have been removed, and usefor functional replacement of damaged tissue. While transplantation of regenerated wholelungs is a far-off goal, we exploit the simpler system of the trachea with which we haveextensive expertise while addressing key issues that will set the foundation for future clinicalapplication of whole lung grafts. At the end of the funding period, we expect to begin clinicaltranslation of a functional tracheal biograft used to address small airway and larger trachealdefects, respectively. The optimized tracheal bioreactors developed can result in commercialproducts via licensing to already existing lung biotech companies or through companycreation ventures with focus on enhanced organ-specific bioreactors. In addition, thedevelopment of a computational model of fluid flow using a computerized geometrical modelsof vascular (and airway) networks will allow in silico experimental programs to explorestrategies for targeted cell delivery. Models developed here have the potential for significantimpact in lung tissue engineering, and can be applied to research groups focused on otherorgans. Completion of this work will set in motion a therapeutic strategy with the potential tosave lives and vastly improve the quality of life of Canadians suffering from end-stage lungdisease.