Tsai, Kai-Jen; (2023) Development of 3D bioprintable collagen for tracheal tissue engineering. Doctoral thesis (Ph.D), UCL (University College London).

Text Final PhD Thesis KJ Tsai 2023.pdf - Other Access restricted to UCL open access staff until 1 October 2026. Download (95MB)

Abstract

In recent decades, addressing human tracheal diseases has driven researchers to focus on developing biomimetic scaffolds and biomaterials. Additive manufacturing and materials science technology, particularly bioprinting, provide promising solutions by creating three-dimensional living cell and biomaterial constructs resembling native biological trachea. Collagen, a commonly used biomaterial in tissue engineering and clinical applications, is biocompatible, biodegradable, and has low allergenicity. However, its weak mechanical properties present a challenge as a single component in bioink for bioprinting applications. Thus, developing bioink with optimal printability, structural integrity, resolution, and cell viability is critical. This thesis explores various techniques to enhance collagen hydrogel's mechanical and printability properties for additive manufacturing applications. Finally, a novel, concentration tuneable, and easily handleable pure collagen bioink compatible with direct micro extrusion-based bioprinting has been developed and presented. Following the collagen fibril alignment induced by micro extrusion, the collagen bioink exhibits high cell viability, structural accuracy, and guided cell orientation without using chemical crosslinkers. Furthermore, the thesis investigates the potential use of collagen bioink in human tracheal regeneration by utilising a 3D bioprinted co-culture of human bronchial epithelial cells and lung fibroblasts embedded in collagen bioink. The co-cultured cells were maintained for up to 28 days in an air-liquid interface (ALI) environment, demonstrating a successful submucosal three-dimensional model. In conclusion, the thesis proposes a novel, pure, dense collagen bioink with suitable printability and mechanical strength for bioprinting three-dimensional constructs directly. The findings also highlight the potential of incorporating this bioink into human airway 3D modelling strategies to improve the fabrication process and reepithelialisation. The use of collagen bioink and 3D bioprinting could provide a more efficient and effective method for creating personalised tracheal scaffolds, which has significant implications for regenerative medicine and drug screening.

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