Year: 2024
Type: dissertation
Abstract: The goal of tissue engineering and 3D bioprinting is to develop in vitro platforms that can recapitulate native tissue environments with essential physiological mechanical and biochemical cues (e.g., shear stress, dynamic stretching, etc.) and accurate cell depositions. Tubular/hollow structures (e.g., airway, alveoli sac, bile duct, blood, and lymphatic vessel) are the basic structural and functional units of virtually all organs in animals and humans. These structures are fundamentally important in developing, maintaining, and regenerating functional tissues. While many approaches (e.g., coaxial extrusion) have been developed regarding the fabrication of such tubular structures, they are limited in applying low-concentration, unmodified, and cell-laden ECM-based biomaterials because of their slow fibrillogenesis kinetics and poor shear thinning behavior. In this thesis, we have developed a microfluidic-enabled bioprinting approach to achieve the continuous, template-free conversion of collagen, elastin, and fibrinogen solutions into tubular structures of tailored size, mechanical strength, and heterogeneous spatial organization. Both device level and tissue level functions are demonstrated by the building of all-ECM valves and pumps, endothelial or epithelial barriers on the tube lumen. Integrated with a custom-designed thermoplastic tube hosting device and airflow system, confluent human airway bronchial epithelium (HBE) was developed and further matured during long-term (up to 2 weeks) air liquid interface (ALI) culture under physiological dynamic airflow. Especially, these soft collagen tubular structures' collapsible, stretchable, and perfusable nature allow airway epithelium injury study within both overdistension as well as collapse and reopening during mechanical ventilation. Correlations among the transmural pressure, tube configuration, collapse and reopening dynamics, and the effect of surfactants are presented. Significantly, using this model, we observed an intensified severity of alveolar injury resulting from the repetitive collapse and reopening, compared to the overdistension. Overall, the presented approach enhances our understanding of lung physiology, especially for ventilation-induced lung injury, while holding promise for broad application in 3D organ-on-a-chip for various tubular tissues.
Source: TSpace (University of Toronto)
Author: Gao, Wuyang
Institution: University of Toronto
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7132885004