The effect of substrate topography on skeletal stem cell behaviour

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.

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Identifiers

ORCID for Richard Oreffo: orcid.org/0000-0001-5995-6726

ORCID for Tilman Sanchez-Elsner: orcid.org/0000-0003-1915-2410

ORCID for Rahul Tare: orcid.org/0000-0001-8274-8837

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