Developing a PEG-based Hydrogel for the 3D culture of human colonic organoids

Sandy, Joseph (2019) Developing a PEG-based Hydrogel for the 3D culture of human colonic organoids. Masters thesis, University of East Anglia.

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Abstract

Human intestinal epithelial organoids are an emerging tool, both in research and in a clinical environment. Due to their structural and functional similarity to physical organs, human intestinal organoids (HIOs) are utilised to model the complexities of human disease pathology including colorectal cancer and inflammatory bowel disease, of which for both, the site of initiation is the colonic epithelium. Current culture methods for HIOs are dependent on growth in an ill-defined, tumour-derived extracellular matrix (ECM), that is of animal origin; which has confounded the use of organoids in a translational and regenerative medicine capacity. There is the therefore, growing appreciation for the use of chemically defined, synthetic hydrogels which have been optimised to support the growth and development of HIOs. In this study, we demonstrate the ability of a synthetic, fully defined hydrogel, based on the reaction between four-armed, thiol and maleimide-terminated poly(ethylene glycol) (PEG) macromers to support the three-dimensional growth and expansion of HIOs. We explore the effects of altered hydrogel parameters such as matrix stiffness and porosity on organoid growth and demonstrate the potential of functionalising inert PEG hydrogels, through assessing organoid growth and survival in response to the inclusion of degradable peptides and human recombinant ECM proteins in the matrix. Our research shows the potential of PEG-based hydrogels to overcome the limitations of current organoid culture systems and suggests a foundation by which PEG hydrogels can be further optimised to support the long-term growth and expansion of HIOs.

Item Type:	Thesis (Masters)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	11 Mar 2021 09:07
Last Modified:	11 Mar 2021 09:07
URI:	https://ueaeprints.uea.ac.uk/id/eprint/79437
DOI:

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