Rosebrugh Bldg, Toronto, ON M5S 3G9
Room: RS 211
There are clinical situations in which it would be desirable to replace hollow organs such as tracheae with functional substitutes. Pathologies affecting more than 50% of the tracheal length including large stenosis, malignancy, and traumatic injury usually require long-term dependence on tracheostomies since conventional means of reconstruction are inadequate. These situations seriously deteriorate the patient’s quality of life and increase the medical and social costs. Engineered biological scaffolds are a promising alternative for tracheal transplantation. However, despite recent advancements, successful epithelialization – indispensable to avoid
tracheal stenosis, collapse, fibrosis and infections upon transplantation – remains a challenge to graft success. In our work, we aim to optimize the re-epithelialization of tracheal scaffolds by defining the critical shear stress range for adequate adherence and proliferation of the epithelium. To this end, a double-chamber bioreactor is used to accurately control the mechanical stimulation of tracheal constructs, with the goal of recapitulating the host environment. We will characterize re-epithelialized porcine tracheal grafts seeded with HTECs with respect to cell morphology and homogeneous seeding and evaluate the effect of shear stress on cell adhesion, viability and proliferation with different flow rates for dynamic perfusion-cell seeding of de-epithelialized tracheal grafts. As of now, we have re-epithelialized a tracheal graft within a redesigned doublechamber rotating bioreactor with a sensor to monitor the flow rate and, indirectly, the resulting tracheal lumen wall shear stress. The process is currently undergoing improvements, and is expected that ongoing computational fluid dynamics simulations will allow us to enhance reepithelialization outcomes by optimizing the fluid delivery system.