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Bennet, Tanya Jane

University of British Columbia

Over the years climate change has led to an increase in the occurrence and frequency of forest fires worldwide. As these events create smoke containing harmful particulates and gases that are difficult to avoid and can travel long distances, they can have a tremendous impact on public health. For those with pre-existing respiratory diseases the risks associated with exposure are heightened as exposure can exacerbate symptoms resulting in hospitalization and disease progression. To advance our understanding of smoke related risks to respiratory health, there is a need for more physiologically relevant in vitro models, especially those compatible with realistic aerosol-based exposures. Current microfluidic lung-on-a-chip technologies have emerged as promising tools for exposures, however their lack of a realistic 3D ECM and/or vasculature limits their ability to capture cell-cell and cell-ECM interactions. The work in this dissertation focuses on the development of a tri-culture microfluidic in vitro model of the human small conducting airways compatible with aerosolized wood smoke exposure. The airway-on-a-chip leverages a compartmentalized microchannel design in combination with a lumen patterned, cell-laden hydrogel to mimic the airways. The combination of photopolymerizable hydrogel and sacrificial molding enables the device to replicate the airway’s 3D ECM and microarchitecture including the microvasculature which is achieved by using the lumen structure as a vessel template. The hydrogel selection process in which potential hydrogels were assessed by comparing their properties to the native lung ECM is described within this dissertation. Integration of the hydrogel into the microdevice was validated by ensuring that the cells that make up the airway-on-a-chip were healthy and viable, as well were able to recapitulate key biological responses. A controllable dynamic microenvironment and recapitulation of physiological flows and flow-related shear stresses was achieved via two pump-based flow systems. Novel wood smoke exposures performed on the airway-on-a-chip demonstrated the microdevices ability to mimic in vivo-like exposure and recapitulate wood smoke-induced cell damage and inflammation. The dissertation also demonstrates that using a biodegradable film to separate vertically stacked microchannels rather than a traditional synthetic membrane enables direct epithelial-ECM interactions and creates a model free of non-physiological materials at cell-cell and cell-ECM interfaces.

Text

2024-03-18

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87591

Biomedical Engineering

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/