Bone defects resulting from non-unions, fractures, significant revision joint replacements, tumour resection and osteolysis present a clinical problem. While autografts are considered the gold standard, ubiquitous use of this reparative technique is limited by graft supply and site morbidity. Recent progresses in tissue engineering using stem cells, bone enhancing molecules and gene therapy have provided more hypotheses for bone defect treatment. In vivo assessment to test these hypotheses requires animal models to mimic human conditions. Immunodeficient or nude animals have the advantage of hosting materials from human and other xenographic origins without immuno-intolerance or rejection. A thorough understanding of the biology in nude animals is vital for the further advancement of connective tissue healing and regeneration strategies. Nude mice are excellent xenographic hosts for in- vivo characterisation and provide a reproducible animal source. The immune deficiencies of nude compared to normal animals may however, influence bone healing and need to be addressed. This dissertation (a) investigated potential bone defect models in nude mice and nude rats (b) incorporated the selected bone defect model to evaluate the effect of T cell deficiency and age on bone defect healing in nude animals (c) determined the feasibility of a critical size defect (CSD) in nude mice. A distal-femur-condylar-defect (DFCD) model was successfully performed in nude mice and rats. The model was found to have some advantages as a bone defect model: (1) located at a weight-bearing skeletal site (2) no requirements for an internal or external fixator (3) does not obstruct or limit mobility (4) location is not in close proximity to any major organs such as the brain (5) easy identification of surface anatomy (6) defect size is standardised and reproducible (7) does not require lengthy and complicated surgery and (8) cost effective. This dissertation confirmed that bone healing in nude mice is similar to that of normal immunocompetent mice. Absence of T lymphocytes did not delay or inhibit bone repair. Use of older nude mice did not seem to affect the healing rate, in contrast to older normal mice, which showed delay in bone healing in the initial phase. Establishment of critical sized defects in mice at a weight-bearing location was not feasible due to the robust healing of murine. This dissertation recommends that the DFCD model could be utilized for the assessment of xenogenic materials at early time point.
| Identifer | oai:union.ndltd.org:ADTP/282488 |
| Date | January 2005 |
| Creators | Gan, Jade Ho Yue, School of Biomedical Engineering, UNSW |
| Publisher | Awarded by:University of New South Wales. School of Biomedical Engineering |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Jade Ho Yue Gan, http://unsworks.unsw.edu.au/copyright |
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