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Engineering Epithelial Microenvironment

Airway epithelium Tracheal resection and reconstruction is the gold standard to repair short injuries caused by disease and physical injury; however there are currently no reliable clinical treatments for reconstructing large segments of injured trachea. In recent clinical trials, decellularized tracheal allografts and tissue-engineered scaffolds have been implanted with successful results to treat large tracheal defects. While the results of these trials suggest that scaffolds functioned as a stable tube for airflow transfer, recipients were susceptible to recurrent infections and mucous impaction after the surgery, which may be in part due to incorrect organization and hence dysfunction of the airway epithelium. The factors controlling optimal epithelial maturation and organization in these replacement airways have barely been explored despite the fact these devices are being used clinically. In collaboration with Dr. Thomas Waddell at Toronto General Hospital, we are examining the impact of exposing maturing epithelium to controlled architectures that alter the distribution of physical forces within the tissue. Our studies aim to examine the hypothesis that architecture and resulting changes in physical forces within the tissue will influence the growth, organization and functional maturation of the epithelial cells, grown from primary airway progenitor cells on engineered basement membranes. Understanding the impact of physical forces during tissue development will provide a novel strategy for improving the quality and clinical utility of engineered epithelial tissues.

3T3 Cytoskeleton Organization on Grooved Substrates

Topographically grooved gel inserts for aligning epithelial cells during air-liquid-interface culture.Soleas JP, Waddell TK, McGuigan AP., Biomater Sci. 2015 Jan;3(1):121-33.

Cilia Alignment under Static and Flow Conditions

A microfluidic device to apply shear stresses to polarizing ciliated airway epithelium using air flow.Trieu D, Waddell TK, McGuigan AP., Biomicrofluidics. 2014 Nov 14;8(6):064104.