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Title: The effect of experimental diabetes on guided bone regeneration
Author: Retzepi, Maria
ISNI:       0000 0004 2675 9648
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2009
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The aim of the present PhD thesis was to investigate the impact of uncontrolled and controlled experimental diabetes on the neo-osteogenesis and bone regeneration potential following Guided Bone Regeneration (GBR). Wistar strain rats (n=128) were allocated in three experimental groups: a) streptozotocin-induced, uncontrolled diabetes; b) systemic insulin controlled diabetes; c) systemic health. The impact of the diabetic status on the neo-osteogenesis and on the bone regeneration potential were evaluated histometrically in GBR treated models of de novo mandibular bone formation and regeneration of critical size calvarial defects respectively. Genome-wide microarray analysis was conducted in tissue samples obtained from GBR treated calvarial defects during the early healing stages. Following application of the GBR therapeutic principle, significant neo-osteogenesis and regeneration of critical size osseous defects were observed histologically and morphometrically, even in the presence of uncontrolled diabetes. Nonetheless, the diabetic status was associated with lower outcome predictability, which was improved via systemic insulin mediated glycaemic control. Uncontrolled diabetes compromised the initial stages of intramembranous bone regeneration following GBR, as evidenced by aberrations in fibrin mesh organisation, inflammatory and mesenchymal cells influx and woven bone formation. In parallel, the uncontrolled diabetic condition featured downregulation of genes encoding chemoattractants and inflammatory mediators during the inflammatory phase of the GBR healing process. Further, pathways related to cell division, energy production and osteogenesis were underexpressed during the proliferative phase, while the NF-kB and Wnt signalling pathways were misregulated. The insulin controlled diabetic state enhanced granulation tissue formation and osteogenesis and upregulated genes encoded growth factors and for extracellular matrix proteins during the early healing phases. It is suggested that, although experimental diabetes may compromise the initial stages of osteogenesis, GBR treatment can provide an environment permissive for significant, even though delayed, bone formation. Insulin mediated glycaemic control may enhance the bone regeneration potential in the diabetic status. Genome-wide expression profiling revealed perturbed pathways in GBR healing depending on the metabolic status, which may be applied in the design of novel therapeutic strategies for the reconstruction of osseous defects in diabetic patients.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available