• Login
• Admin

Mosses, Dominic (2024) Additive manufacturing of multifunctional materials to examine their effects on the phenotype of stem cell derived cardiomyocytes. PhD thesis, University of Nottingham.

PDF (Thesis - as examined) - Repository staff only - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader Available under Licence Creative Commons Attribution. Download (9MB) Request Thesis

Abstract

Human induced pluripotent stem cell (hIPSC) technologies are set to revolutionise research into cell biology. This is due to the ethical methods by which they are obtained and the ability to differentiate them into any cell type of the three germ layers. Many non-proliferative human cell types can be differentiated from hIPSCs. This is particularly apparent when deriving cardiomyocytes from hIPSCs (hIPSC-CMs). As a cell type lacking proliferative or regenerative capacity, research into cardiomyocytes will doubtless benefit from hIPSC technologies. This benefit should be seen in the development of novel experimental models and cellular therapies. However, despite almost ten years passing since they were first described, new therapeutic and experimental technologies derived from hIPSC-CMs are slow to materialise. This is partly due to outcomes of differentiation processes.

Currently differentiation of hIPSC-CMs is driven by biochemical methods upon standard tissue culture materials. These in vitro hIPSC-CM differentiation technologies fail to accurately replicate the complex environment required to guide behaviour. This results in immature and functionally compromised cell types. The lack of multifunctional substrate availability therefore poses a significant challenge to controlling cells during culture.

To address this issue, composite materials with defined 3D architecture, topography, mechanical, chemical, and electric properties were developed using high-resolution 3D-printing. These materials were used to form in vitro experimental tools that support attachment of human induced pluripotent stem cell-derived cardiomyocytes. We hypothesise that the design freedom of 3D printing, coupled with bespoke ink development, will allow the chemistry, elasticity topography and electrical conductivity of these tools to be unilaterally varied. Through incorporation of electrical stimulation, we introduce a further signalling moiety to cultured cells. We further hypothesise that the contributions of these material functionalities and electrical stimulatory will drive hIPSC-CM maturity.

In this work we therefore examine the ability to tune the biologically relevant functionalities of novel hIPSC-CM culture tools. We show that material conductivity, elasticity, surface chemistry and topography can be accurately varied independently of one another. We then use these newly developed cell culture substrates to establish how to tune hIPSC-CM maturation. Several parameters are examined as functional indicators of maturation including sarcomere length and beat amplitude and kinetics. We discover that surface chemical signalling is the primary driver of morphological and functional maturity. However, in the presence of electrical stimulation all material functionalities are overridden and beat kinetics of cell populations are homogenised. The work has implications for future tissue engineering technologies, which could be used to improve the accuracy of existing cardiac drug screening models.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Rawson, Frankie Alexander, Morgan Hague, Richard Wildman, Ricky Denning, Chris
Keywords:	stem cells, cell biology, cell culture tools, cardiomyocytes
Subjects:	Q Science > QH Natural history. Biology > QH573 Cytology
Faculties/Schools:	UK Campuses > Faculty of Science > School of Pharmacy
Item ID:	77949
Depositing User:	Mosses, Dominic
Date Deposited:	18 Nov 2025 09:06
Last Modified:	18 Nov 2025 09:06
URI:	https://eprints.nottingham.ac.uk/id/eprint/77949

Actions (Archive Staff Only)

Edit View