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Title: Characterisation of the biological potential of fracture non-union tissue
Author: Kelly, Michael
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2012
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Over 1.1 million fractures are estimated to occur annually in England and Wales. Up to 10% of these are likely be complicated by a delay or failure to heal with significant health and financial implications. Definitions of fracture non-union are not clear and although the Weber and Cech classification is still the definitive, misinterpretations remain common. Current treatment is surgical but the morbidity, particularly where autologous bone grafting is used, can be as high as 30%. Novel approaches are being tried but few of the strategies have made the translational impact that the laboratory and animal model data suggested. The work presented here investigates the feasibility of quantifying the biological potential of non-unions in patients and in a validated, in vivo model. Hypothesis: there is quantifiable biological potential in fracture non-union tissue that can be stimulated leading to osseous union by closed percutaneous injection of induction factors. Tissue from patients with non-infected fracture non-union undergoing treatment was examined to determine the feasibility of quantifying gene activity in small samples of non-union gap tissue. Non-union tissue from the animal model of an established non-union was examined to assess its osteoblastic potential by culture of extracted cells. Ortho bio logical agents that have shown great potential in gap models of non-union (BMP2 delivered in a viral construct (AdBMP2) and the thrombin peptide, TP508) were assessed to determine their efficacy in a clinically analogous model of fracture non-union. Quantifiable metabolic activity was found in the small samples of human non-union tissue. There was potential to correlate this to the histomorphometric architecture of the tissue. Cells extracted from the gap tissue of a non-union site in the rat model demonstrated osteoblastic potential in vitro. However, percutaneous injection of the orthobio logical agents into the non-union site in vivo failed to stimulate healing. The tissue at the site of a fracture non-union has a quantifiable metabolic activity that may have great clinical application and research benefits. Tissue from the non-union site of the animal model did demonstrate osteoblastic capacity but attempts to effect healing using percutaneously injected orthobiological agents that have previously shown potential, failed. This may be due to the chronic timepoint chosen to replicate the clinical situation. Further work is necessary to determine the prognostic potential of the gene assays and to continue to characterise the biological potential of the non-union tissue so that interventions can be more accurately directed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available