A novel 3D bioprinted model of Alzheimer's disease using patient derived hiPSC derived neurons in a fibrin-based hydrogel bioink

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dc.contributor.authorWalters-Shumka, Jonathan
dc.date.accessioned2026-02-09T18:23:36Z
dc.date.available2026-02-09T18:23:36Z
dc.date.issued2021
dc.description.abstractAlzheimer's Disease (AD) is an age-related neurodegenerative disease that does not yet have any disease modifying treatments. Because there is a high cost associated with the disease and because the prevalence of AD is increasing, the need for new drugs to treat AD is high. Many drugs have passed pre-clinical trials only to fail in clinical trials. Most of the pre-clinical trials have been conducted on 2D monolayer cell culture and animal models. The failure of these drugs in clinical trials indicates that these two kinds of models do not accurately model AD. A 3D bio printed hydrogel model of AD which uses familial AD (fAD) patient derived human induced pluripotent stem cells (hiPSCs) can provide a more accurate model. Here we describe the first steps in creating a novel 3D bio printed model of AD using hiPSCs derived from a patient with a fAD mutation on the APP gene and a healthy control hiPSCs line. We 3D printed ring-shaped constructs 8mm high and 1cm wide containing fAD and healthy patient derived hiPSC derived neural progenitor cells (NPC's). The 3D printed constructs were then differentiated for 45 days in a cortical neuron differentiation medium. We have shown that both the AD and healthy cell lines are able to produce neurite extensions and stain positive for the early neuronal cytoskeleton marker ß tubulin III in our bioink. This indicates that the cells have successfully differentiated into neurons within our bioink. We have also observed axonal boutons, and dendritic spines on both cell lines and an axonal swelling on an AD neuron which is associated with early AD pathology. These findings confirm past work that healthy and diseased patient derived hiPSC derived neurons can be differentiated in hydrogel scaffolds. This is however, the first time this has been done in 3D printed hydrogel scaffolds. This is also the first time that dendritic spines and axonal swellings have been observed in a 3D hydrogel model of AD.
dc.description.reviewstatusUnreviewed
dc.description.scholarlevelUndergraduate
dc.identifier.urihttps://hdl.handle.net/1828/23285
dc.language.isoen
dc.subject.departmentDepartment of Biology
dc.titleA novel 3D bioprinted model of Alzheimer's disease using patient derived hiPSC derived neurons in a fibrin-based hydrogel bioink
dc.typeHonours thesis

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