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dc.contributor.advisorNoble, Brendon
dc.contributor.advisorMann, Valerie
dc.contributor.advisorTravers, Paul
dc.contributor.authorCameron, Katherine Rachel
dc.date.accessioned2013-10-28T11:08:23Z
dc.date.available2013-10-28T11:08:23Z
dc.date.issued2013-07-06
dc.identifier.urihttp://hdl.handle.net/1842/8051
dc.description.abstractAn increase in degenerative bone disease in an ageing population, combined with a rise in the number of patients suffering from bone defects caused by physical trauma, makes the repair of bone an issue of growing clinical relevance. Current treatments such as autografts and allografts have major drawbacks, including donor site morbidity, limited availability, disease transmission and immune rejection. To overcome these issues synthetic bone grafts have been developed to mimic the mineral phase of bone. Given the significant roles of silicon in bone growth and development there has been great interest in introducing silicon into synthetic bone grafts to enhance their bioactivity. Calcium phosphate based silicate containing grafts have demonstrated enhanced bioactivity, improved physical properties, enhanced protein adsorption and greater bone formation, when compared to non-silicated calcium phosphates such as hydroxyapatite. However, is not clear whether the increased bone formation associated with these materials is the result of greater osteoblast activity or a rise in numbers of osteoblasts resulting from activation and differentiation of stem/ progenitor cells. To answer this question, multipotent stem cells were cultured on silicate substituted calcium phosphate (Si-CaP) and hydroxyapatite (HA). Si-CaP promoted greater cell adhesion and enhanced proliferation when compared to HA. Cells differentiated along the osteogenic lineage on both substrates as evidenced by up regulation of osteoblast specific genes and proteins. However, cells on Si-CaP showed earlier and greater gene expression of all osteoblast genes examined, and greater protein production as detected by immunohistochemistry. Integrin gene expression analysis revealed up regulation of α an d β subunits on both substrates during differentiation. Integrins α5 and β1 expression were greater on Si-CaP than on HA, suggesting preferential binding of fibronectin. The implication of these findings for tissue engineering is clear, suggesting these substrates may be utilized to control stem cell fate in vivo and in vitro without the need for osteogenic supplementation. Furthermore, the increased rate of differentiation seen on Si-CaP may enable the development of novel substrates for osteogenic differentiation of MSC, which may have significant impact in regenerative medicine.en_US
dc.contributor.sponsorEngineering and Physical Sciences Research Council (EPSRC)en_US
dc.language.isoenen_US
dc.publisherThe University of Edinburghen_US
dc.relation.hasversionCameron K, Travers P, Chander C, Buckland T, Noble B. 2012. Directed osteogenic differentiation of human mesenchymal stem/ precursor cells on silicate substituted calcium phosphate. Journal of Biomedical Materials Research Part A . (Published 26th June 2012)en_US
dc.subjectBone graft substitutesen_US
dc.subjectmesenchymal stem cellen_US
dc.subjectosteogenic differentiationen_US
dc.subjectcalcium phosphateen_US
dc.titleCalcium phosphate substrate-directed osteogenic differentiation of mesenchymal stem cellsen_US
dc.typeThesis or Dissertationen_US
dc.type.qualificationlevelDoctoralen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US


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