Year

2018

Degree Name

Doctor of Philosophy

Department

School of Chemistry

Abstract

The human brain is arguably one of the most complex structures known to humankind. To understand the development, function, and dysfunction of this organ, both historical and modern neurological research methods have intrinsic limitations. Modern functional imaging and electrophysiological techniques obtain important data on the structural and functional aspects of specific brain regions but are unable to accumulate biomolecular information, whereas animal models of brain development allow for complete molecular interrogation, but show intrinsic morphological differences compared to native human brain tissue. In vitro modelling of human brain tissue through the differentiation of induced pluripotent stem cells (iPSCs) offers a completely novel method of studying human brain development. iPSCs can differentiate into any somatic cell derived from the three germ layers, and as such, can form cells of specific neural lineages from multiple brain regions. Furthermore, this differentiation in vitro follows the same principles of in utero brain development, and so can be used to model specific genetically-linked neurodevelopmental pathologies such as the epilepsies.

Neural cell differentiation within three-dimensional cell culture scaffolds offers a way of replicating a more in vivo-like microenvironment compared to standard planar culture. Therefore, the generation and optimisation of cytocompatible biomaterials to form these three-dimensional scaffolds will be integral for the future of in vitro neural tissue engineering.

This thesis focuses on the combination of both biomaterial engineering and iPSCbased neurological development to assess the synergy of targeted neuronal cell differentiation within three-dimensional hydrogel environments.

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.