The effect of experimental diabetes and glycaemic control on guided bone regeneration: histology and gene expression analyses

Authors

  • M. Retzepi,

    1. Centre for Oral Clinical Research, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, UK
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  • E. Calciolari,

    1. Centre for Oral Clinical Research, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, UK
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  • I. Wall,

    1. Regenerative Medicine Bioprocessing Unit, UCL Advanced Centre for Biochemical Engineering, London, UK
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  • M. P. Lewis,

    1. National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
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  • N. Donos

    Corresponding author
    1. Centre for Oral Clinical Research, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), London, UK
    • Corresponding author:

      Prof. Nikolaos Donos, DDS, MS, FHEA, FDSRCSEngl., PhD

      Centre for Clinical Oral Research, Institute of Dentistry

      Barts and The London School of Medicine and Dentistry

      Queen Mary University of London (QMUL)

      Turner Street, London, E1 2AD, UK

      Tel.: +44 (0) 2078823076

      Fax.: +44 (0) 2078823076

      e-mail: n.donos@qmul.ac.uk

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Abstract

Objectives

To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR).

Material and methods

Ninety-three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5-mm defect was created at the mid-portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis.

Results

Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38–42%) and newly formed bone (54–61%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified.

Conclusions

Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population.

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