Limitations in current model systems for researching bone repair have hampered the development of alternative clinical therapies. This thesis aimed to develop and validate an ex vivo rat mandible model, to investigate specific molecular and cellular processes involved in bone repair. Maintenance of cell and tissue architecture and viability was shown within mandible slices cultured for up to 21 days, both intact and fractured. Autoradiographic studies showed that resident cells were actively synthesising and secreting proteins, and cells of the osteoblast lineage were shown to survive throughout the culture period. The model was responsive to exogenously added growth factors TGF-p1 and BMP-2, with increased cellular migration / proliferation and expression of bone matrix proteins observed. A second model system, an in vitro bone slab cell culture system, demonstrated that endogenous growth factors could be released from the matrix of bone by chemicals such as EDTA, calcium hydroxide, and sodium hydroxide. Different growth factor release kinetics were observed with each treatment, and released growth factors were capable of actively influencing the behaviour of osteogenic cells. Pre-treatment of mandible slices with these chemical treatments yielded similar results, with an observed increase in cell number, proliferation, and bone matrix protein expression. The ex vivo mandible model developed within this study may represent an ideal system for investigating specific processes of bone repair, as well as a promising alternative to in vivo testing of novel clinical therapeutics.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:584762 |
| Date | January 2009 |
| Creators | Smith, Emma Louise |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/55910/ |
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