The biology of tendons has been extensively investigated previously. Many studies have looked into the development and healing of tendons. An overall picture of the events in tendon development and healing, in terms of recently recognised functional molecules is missing, particularly in a single model. The recent understanding of the importance of metalloproteinases and other enzymes in ECM degradation suggests they may be of importance in tendon healing and development. Another unexplored area with relevance to wound healing and development is the functional integrin molecules. This thesis looked at the spatial and temporal localisation of a wide range of functional molecules and at cell proliferation. The subject groups were tendon development, from the limb bud to juvenile animal, and a defined reproducible adult healing model, with time points to six months. The study was then extended to fetal tendon healing. The results were analysed qualitatively using immunohistology and the findings were supported by histological and ultrastructural analysis, which reproduced the findings of previous studies and allowed novel observations. Adult tendon healing was accessible to quantitative analysis, which added further weight to the results. Tendon wounds in the adult model were noted to be asymmetrical in terms of tissue fibrillation, and immunohistology on opposite sides of the wound. Observations of integrin and cytoskeletal patterning in the wound, suggested mechanical load may have modulated this effect. A further study looked at a defined set of wound models. These modified the mechanical load and tissue perfusion of the wound to reproduce the effects in symmetrical wounds. The results showed that the spatial and temporal localisation of collagens, growth factors, enzymes and integrins and cell proliferation were modulated over a six month healing period. This was supported by quantitative analysis. Similar, but different effects were noted in development and fetal healing. Collagen types had a similar pattern in the three models, although the results demonstrated profound differences in timing and events surrounding new matrix production. The results of the wound modulation study using a cell proliferation marker, immunohistology, Western blots and zymograms of these wounds, were analysed and found to show marked differences in morphology, enzyme production and cell proliferation. The results excluded growth factors and tissue perfusion as the cause when these factors were controlled for. Significant (p<O.05) differences were observed between wounds. The novel results are discussed, showing modulation of several collagens, MMPs, TIMPs, cathepsins, growth factors and integrins during tendon healing, development and fetal healing with reference to other studies and proposals for the modulation of tendon healing principally by mechanical forces on the wound are made. The observation is made that tendon fetal and adult healing are profoundly different. This is consistent with other models of fetal healing. A novel proposal from the results based on matrix organisation is made for the dissimilar nature of adult and fetal wound healing.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:488287 |
| Date | January 2001 |
| Creators | Brooks, Jonathan Peter |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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