The University of Southampton
University of Southampton Institutional Repository

The effect of substrate topography on skeletal stem cell behaviour

The effect of substrate topography on skeletal stem cell behaviour
The effect of substrate topography on skeletal stem cell behaviour
Advances in modern medicine have led to a welcome increase in life expectancy. Unfortunately, this is associated with an increase in diseases of the elderly including osteoporosis and osteoarthritis. Current treatment is met with mixed success and invasive joint replacements have limited lifespan. New strategies for treatment of degenerative bone disease are urgently needed.

Skeletal tissue has a remarkable capacity to regenerate and this has been ascribed to the skeletal stem cell (SSC) which can differentiate towards osteogenic, chondrogenic and adipogenic lineages. Given the ability of SSCs to differentiate into osteoblasts, SSCs have been studied for their potential to treat complications of degenerative bone disease. In order to use SSCs in the clinic, an osteogenic population must be selected from the total SSC population. One approach to do this has harnessed the potential of surface topographical cues to drive cell fate and function and enhance osteogenic differentiation of SSCs.

This thesis details the potential for SSCs to differentiate into osteoblasts and the potential to employ topographical cues to enhance or modulate this process. A range of topographical cues have been examined for SSC fate and function on different substrates including a near square arrangement of nanopits, cell-bioimprinted surface, and a biomimetic approach - nacre and prism surfaces. The near square nanopit surface was found to not induce osteogenic differentiation. Bioimprinted surface material was found to have a moderate effect of SSC behaviour and topography of these surfaces had a limited effect on SSC behaviour. Nacre surface topography alone were observed to modulate expression of osteogenic markers as well as upregulation of metabolomic profile to a level similar to chemically induced osteogenic differentiation, however a small data set was studied for these experiments. The prism surface was thought to possibly maintain SSC phenotype, as metabolomic activity decreased when cultured on these surfaces. To conclude, nacre topographical surfaces showed promising results to enhance osteogenic differentiation however this must be studied further, in an in vivo model in order to fully understand its potential for a topographical surface in treatment of degenerative bone disease.
University of Southampton
Waddell, Shona, Jane
04a26ab3-adb1-46c2-8924-255be0523515
Waddell, Shona, Jane
04a26ab3-adb1-46c2-8924-255be0523515
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Tare, Rahul
587c9db4-e409-4e7c-a02a-677547ab724a

Waddell, Shona, Jane (2018) The effect of substrate topography on skeletal stem cell behaviour. University of Southampton, Doctoral Thesis, 285pp.

Record type: Thesis (Doctoral)

Abstract

Advances in modern medicine have led to a welcome increase in life expectancy. Unfortunately, this is associated with an increase in diseases of the elderly including osteoporosis and osteoarthritis. Current treatment is met with mixed success and invasive joint replacements have limited lifespan. New strategies for treatment of degenerative bone disease are urgently needed.

Skeletal tissue has a remarkable capacity to regenerate and this has been ascribed to the skeletal stem cell (SSC) which can differentiate towards osteogenic, chondrogenic and adipogenic lineages. Given the ability of SSCs to differentiate into osteoblasts, SSCs have been studied for their potential to treat complications of degenerative bone disease. In order to use SSCs in the clinic, an osteogenic population must be selected from the total SSC population. One approach to do this has harnessed the potential of surface topographical cues to drive cell fate and function and enhance osteogenic differentiation of SSCs.

This thesis details the potential for SSCs to differentiate into osteoblasts and the potential to employ topographical cues to enhance or modulate this process. A range of topographical cues have been examined for SSC fate and function on different substrates including a near square arrangement of nanopits, cell-bioimprinted surface, and a biomimetic approach - nacre and prism surfaces. The near square nanopit surface was found to not induce osteogenic differentiation. Bioimprinted surface material was found to have a moderate effect of SSC behaviour and topography of these surfaces had a limited effect on SSC behaviour. Nacre surface topography alone were observed to modulate expression of osteogenic markers as well as upregulation of metabolomic profile to a level similar to chemically induced osteogenic differentiation, however a small data set was studied for these experiments. The prism surface was thought to possibly maintain SSC phenotype, as metabolomic activity decreased when cultured on these surfaces. To conclude, nacre topographical surfaces showed promising results to enhance osteogenic differentiation however this must be studied further, in an in vivo model in order to fully understand its potential for a topographical surface in treatment of degenerative bone disease.

Text
Shona Waddell Thesis 230319 no comments - Version of Record
Available under License University of Southampton Thesis Licence.
Download (17MB)

More information

Published date: October 2018

Identifiers

Local EPrints ID: 437079
URI: http://eprints.soton.ac.uk/id/eprint/437079
PURE UUID: fa1ab464-4521-47cb-aaf5-3b94a5dbc606
ORCID for Richard Oreffo: ORCID iD orcid.org/0000-0001-5995-6726
ORCID for Tilman Sanchez-Elsner: ORCID iD orcid.org/0000-0003-1915-2410
ORCID for Rahul Tare: ORCID iD orcid.org/0000-0001-8274-8837

Catalogue record

Date deposited: 16 Jan 2020 17:33
Last modified: 23 Jul 2022 01:58

Export record

Contributors

Author: Shona, Jane Waddell
Thesis advisor: Richard Oreffo ORCID iD
Thesis advisor: Tilman Sanchez-Elsner ORCID iD
Thesis advisor: Rahul Tare ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×