Use this URL to cite or link to this record in EThOS:
Title: Exploring the influence of bioactive glasses on stem cell chondrogenesis for tissue engineering
Author: Littmann, Elena
ISNI:       0000 0004 7656 948X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
Availability of Full Text:
Access from EThOS:
Access from Institution:
The development of smart biomaterials which trigger the differentiation of progenitor cells towards a desired lineage continues to pose a challenge for the material science and tissue engineering communities. In order to design such materials, a better understanding of cell-material interactions as well as knowledge of the key physico-chemical parameters responsible for the determination of cell fate are essential. Bioactive glasses are attractive materials for osteochondral repair applications and are known to impact cell behaviour. Characteristically, bioactive glasses modify their local ionic microenvironment by releasing therapeutic ions when introduced in biological fluids. Such bioactive glass extracts have been shown to trigger specific biological responses in vitro and in vivo. This thesis explores the influence of key bioactive ion species within bioactive glass dissolution products on the behaviour of human mesenchymal stem cells (hMSCs). Firstly, the effect of strontium ions within bioactive glass extracts on metabolic processes in hMSCs is studied following a non-biased approach based on a whole genome mRNA microarray. It is demonstrated that such extracts induce an up-regulation of the isoprenoid biosynthesis pathway in hMSCs causing a multifactorial response beyond lineage commitment opening up new avenues of evaluating cell-material interactions. Secondly, to identify desirable glass compositions for the repair of the osteochondral system, the influence of strontium and/ or magnesium containing bioactive glasses on hMSC chondrogenic differentiation is investigated. Bioactive glass extracts are shown to differentially modify cartilaginous matrix accumulation in hMSC pellets in a composition-dependent manner. Finally, insights into the impact of the hypoxia-mimicking agent cobalt within bioactive glass extracts on hMSC chondrogenic differentiation and (stem) cell behaviour are explored. It is demonstrated that hMSC chondrogenesis in presence of bioactive glass extracts is cobalt dose-dependently reduced. Collectively, the work described in this thesis has contributed to defining the impact of key ions on hMSC behaviour.
Supervisor: Stevens, Molly M. ; Saiz Gutierrez, Eduardo Sponsor: European Commission
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral