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Topic

Optimizing Extrudable Bioinks: Mechanical and Chemical Properties for Tailored Tissue Engineering

Department of Mechanical Engineering

Date & location

• Friday, November 21, 2025

• 8:30 A.M.

• Engineering Office Wing, Room 502

• And Virtual Defence

Reviewers

Supervisory Committee

• Dr. Stephanie Willerth, Department of Mechanical Engineering, ӣ��Ӱ�� (Co-Supervisor)

• Dr. Bosco Yu, Department of Mechanical Engineering, UVic (Co-Supervisor)

• Dr. David Leitch, Department of Chemistry, UVic (Outside Member) 

External Examiner

• Dr. Boyang Zhang, Department of Chemical Engineering, McMaster University 

Chair of Oral Examination

• Dr. Yu-Ting Chen, Department of Mathematics and Statistics, UVic

   

Abstract

Three-dimensional (3D) bioprinting has emerged as a powerful strategy for generating physiologically relevant tissue models that better replicate native cell–matrix interactions than traditional two-dimensional cultures or animal models. Such constructs hold promise for regenerative medicine, disease modeling, and drug discovery, yet the relationships between bioink properties, printing fidelity, and subsequent cellular behavior remain poorly defined. This gap limits rational material design and slows translational progress.

This dissertation focuses on the pre-processing stage of extrusion-based bioprinting, with particular attention to the design and characterization of bioinks. Using a CELLINK BIO X extrusion bioprinter, we systematically investigated how rheological descriptors, chemical functionalities, and nanoscale crystallinity govern construct fidelity and the fate of encapsulated cells. A range of fibrin-, alginate-, carboxymethyl chitosan (CMC)-, and cellulose-based formulations was developed to investigate how material properties govern bioprinting performance and cellular responses. In Chapter 2, a 3D bioprinted skin model was established as a case study, revealing that cellular organization and cross-talk not only shaped construct viability but also actively influenced the rheological properties of the bioink, demonstrating a reciprocal interaction between cells and material mechanics. Chapter 3 expanded this investigation by engineering fibrin–alginate formulations and showing that rheological features, particularly elastic modulus, were powerful predictors of early biological outcomes: softer hydrogels favored initial viability, while intermediate stiffness supported proliferation and neuronal activity. These descriptors were then used to train a support vector regression model that accurately predicted cell viability, proliferation, and functionality across fibrin–alginate formulations and generalized to chemically distinct systems, identifying F20A1 as an optimal candidate validated experimentally by enhanced neuronal identity and neurite outgrowth. In Chapter 4, chemical functionality emerged as a critical determinant of long-term outcomes: N,O-CMC bioinks supported >80% viability and robust differentiation into neurons and astrocytes by day 30, whereas O-CMC constructs showed declining viability (~35%) and persistence of progenitor markers. Finally, Chapter 5 addressed the influence of nanoscale structure, showing that cellulose nanocrystals enhanced shear-responsiveness, porosity, and shape fidelity, whereas cellulose nanofibers increased stiffness but impaired extrusion.

In conclusion, this work demonstrates that bioink performance arises from the interplay of mechanics, chemistry, and nanostructure. By linking these material features to biological outcomes, it establishes a predictive framework for rational bioink design, advancing the development of reproducible, functional, and clinically relevant 3D bioprinted tissue models.