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Title: The role of chemistry and strut porosity and the influence of serum proteins in modulating cellular response to bone graft substitutes
Author: Castagna, Viviana
ISNI:       0000 0004 5355 3039
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2015
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The objective of this thesis was to investigate the role of hydroxyapatite and silicate-substituted hydroxyapatite synthetic bone graft substitute (SBG) material properties in modulating the processes of protein adsorption and desorption, and their combined role in the subsequent regulation of cell attachment, proliferation and differentiation on the surfaces of these materials in vitro. As a result of their purported role in promoting osteogenic behaviour in vivo the materials parameters selected for investigation were chemistry (stoichiometric hydroxyapatite (HA) versus 0.8wt% silicate-substituted hydroxyapatite (SA)) and strut porosity (20% versus 30% strut porosity). Cell attachment and response to different SBG was assessed to samples in the ‘as received’ condition as well as after a series of sequentially varied pre-treatments with solutions of phosphate buffered saline or cell culture media either unsupplemented or in combination with mixed serum proteins and/or Fibronectin (Fn). This enabled investigation of the effect of sample chemistry and strut porosity on mixed serum protein interactions and Fn adsorption under both competitive and non-competitive conditions, and the study of subsequent regulation of cell attachment and response as a consequence of pre-treatment. Results showed that serum protein interactions were key to modulation of cell response to chemistry, and there was evidence that for Fn this may be related to conformational changes in the adsorbed protein rather than its level of enrichment in the protein interlayer. In terms of the materials properties investigated strut porosity was found to be the most dominant factor in the regulation of cell response, where SBG with 30% strut porosity promoted human mesenchymal stem cell (hMSC) osteoblastic differentiation. Moreover hMSC response to SBG with 30% strut porosity seemed to be less sensitive to pre-treatment. In conclusion, the results of these experiments indicate that strut porosity more directly influences the cellular response to HA and SA BGS than chemistry in vitro. Moreover, the role that Fn and other serum proteins have in regulating this response is dependent on the physiological environment and BGS chemistry.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: synthetic bone graft ; material properties ; protein adsorption ; cell attachment, proliferation and differentiation ; serum protein interactions ; strut porosity