The Production And Distribution Of Factors Relating To The Regulation Of Wound Healing In Oral Health And Disease

  • Kevin John Davey

    Student thesis: Doctoral ThesisDoctor of Philosophy


    Background: Wound healing of the oral soft tissues, compared with skin and other epidermal tissues, is associated with enhanced healing capacity and reduced scarring. Angiogenesis is dependent on many angiogenic factors including angiopoietin-1 (Ang-1), migration stimulating factor (MSF) and vascular endothelial growth factor (VEGF), and the inhibitor endostatin. Angiogenesis is an important feature in both wound healing and periodontitis; both known to be compromised by factors including smoking and poorly controlled diabetes.Aims: To investigate whether:i) serum and salivary concentrations of Ang-1, MSF, VEGF and endostatin differ significantly between periodontal health and severe periodontitis, smoking and diabetes.ii) the quantification of vascularity in periapical granulomas (PG) and healthy periodontal ligament (PDL), using different endothelial markers, has value as an index of angiogenesis.

    Methods: Following research ethics approval, 102 adult subjects were recruited and divided into three study groups: systemically healthy (n=53), smokers (n=20) and subjects with diabetes (n=29). Each group was sub-divided into periodontally healthy or those with severe periodontitis. Serum, saliva (whole mouth, unstimulated and stimulated) and gingival crevicular fluid samples were collected. Ang-1, MSF, VEGF and endostatin concentrations were determined using enzyme-linked immunosorbent assays (ELISA). Paraffin-embedded sections of PG and PDL were stained with vWF and CD105, and standard microscopic methods used to quantify vascularity.

    Results: Salivary concentrations of Ang-1 and endostatin are reported for the first time. Salivary concentrations of VEGF were significantly raised in diabetes (p<0.05) and serum endostatin concentrations were significantly reduced in smokers (p<0.001). No significant differences were found in Ang-1 or MSF concentrations between the study groups, in either serum or saliva. No significant differences were found in staining or measures of vascularity between PG-PDL, whilst clear evidence of angiogenesis was found in oral squamous cell carcinoma (OSCC) control samples.

    Conclusions: Smoking and diabetes were found to significantly alter levels of endostatin and VEGF respectively. No evidence in angiogenic activity was found in the PGs and CD105 was not found to be a specific angiogenic marker.
    Date of Award2021
    Original languageEnglish
    SupervisorMark Hector (Supervisor) & Sarah Jones (Supervisor)


    • Periodontitis
    • Angiogenesis
    • Oral Wound healing
    • smoking
    • Diabetes
    • Ang-1
    • MSF (Migration Stimulating Factor)
    • VEGF
    • Endostatin
    • Periapical granuloma
    • Vascularity
    • vWF
    • CD105
    • OSCC

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