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Faculty of Graduate Studies

Farnoosh Kalantarnia

  • M.Sc. (Sharif University of Technology, 2021)

  • B.Sc. (Amirkabir University of Technology, 2018)

Notice of the Final Oral Examination for the Degree of Philosophy

Topic

Extrusion 3D Bioprinting of Brain Tissue: A Step Toward Alzheimer’s Disease Monitoring and Drug Screening

Department of Mechanical Engineering

Date & location

  • Thursday, October 29, 2026

  • 9:00 A.M.

  • Engineering Computer Science Building

  • Room 660 & Virtual Defence

Reviewers

Supervisory Committee

  • Dr. Stephanie Willerth, Department of Mechanical Engineering, University of Victoria (Co-Supervisor)

  • Dr. Mina Hoorfar, Department of Mechanical Engineering, UVic (Member)

  • Dr. Katherine Elvira, Department of Chemistry, UVic (Outside Member)

External Examiner

  • Dr. Todd Hoare, Department of Chemical Engineering, McMaster University 

Chair of Oral Examination

  • Dr. Kurt Smith, School of Exercise Science, Physical and Health Education, UVic

     

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by complex pathological interactions among amyloid beta (Aβ) and tau proteins, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Although conventional 2D cultures are widely used to investigate AD mechanisms, they do not reproduce the spatial organization, cell–cell and cell–matrix interactions, or biochemical gradients present in human brain tissue. These limitations can affect neuronal maturation and the accumulation of disease-associated proteins, making it difficult to reproduce the progressive pathology of AD in vitro. The present study aimed to develop and characterize an extrusion-based 3D-bioprinted neural tissue platform and evaluate its ability to reproduce disease-associated phenotypes using human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs).

The first part of this work focused on optimizing a multicomponent alginate–fibrinogen–aldehyde-functionalized hyaluronic acid bioink for long-term neural culture through a volume-ratiometric approach. Changes in composition significantly influenced physical, mechanical, and structural properties, which in turn affected cellular responses within the constructs. Different formulations supported distinct patterns of cell viability, neurite extension, and neuronal maturation, demonstrating the importance of matching bioink properties to neural tissue requirements.

The optimized platform was then applied to model familial AD using hiPSC-derived NPCs carrying the PSEN2 N141I mutation and its corresponding isogenic control. Cells were differentiated in parallel in 2D cultures and 3D-bioprinted constructs and evaluated at multiple stages of maturation. The PSEN2 N141I cultures reproduced several AD-associated phenotypes, although their magnitude and temporal development differed between 2D and 3D environments. AD cultures exhibited an increased Aβ42/40 ratio, elevated oxidative stress, alterations in mitochondrial membrane potential, and selective changes in inflammatory cytokine secretion.

In summary, this work demonstrates that both bioink composition and the resulting physicomechanical microenvironment play important roles in neural cell behaviour within 3D-bioprinted constructs. It also establishes an optimized hiPSC-derived neural platform capable of reproducing multiple molecular, metabolic, and pathological features associated with PSEN2 N141I AD. The differences observed between the 2D and 3D cultures further highlight the influence of the cellular microenvironment on the development of disease-associated phenotypes. Future incorporation of additional neural, glial, and neuroimmune cell types, together with drug-response studies, may further improve the physiological relevance and translational potential of this platform for mechanistic studies and therapeutic screening in AD.

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