With an increasingly ageing population the requirement for titanium implants will grow. A major challenge is to speed up the rate and strength of osseo-integration. Bioactive glass coated titanium is postulated to improve bone-bonding ability of titanium. However, bioactive glasses have a higher thermal expansion coefficient (TEC) than titanium and are more prone to crystallization during coating process. Therefore, the aim was to develop a bioactive glass coating that matches the TEC of titanium does not crystallize during coating process and forms surface apatite in vivo and in vitro. To achieve these qualities certain compounds (MgO, CaF2 and MgF2 and fluorapatite (FA) crystals) were substituted or added to the glass composition. The glasses were prepared using melt-derived route. The ground glasses were sieved to obtain less than 45 μm diameter glass particles and this powder characterised using X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Glass rods were cast to measure TEC, glass transition temperature (Tg) and softening temperature (Ts) using Dilatometry. Glass structure was investigated by measuring glass density and oxygen density. The apatite-forming ability of the glass powder was assessed in both Tris-buffer and simulated body fluid (SBF). Filtrates were analysed by inductively coupled plasma spectroscopy (ICP). Titanium disks were coated with bioactive glass/composites using the enamelling technique. Coated samples were characterised by (XRD, FTIR) and scanning electron microscopy (SEM-EDS). Bioactivity of coating samples was studied after 1 month immersion in Tris-buffer solution or SBF. Biocompatibility assays of glass coatings were assessed using UMR106 osteoblast-like cells and a fibroblast cell line. The results generated some interesting findings – firstly it is possible to produce glasses with comparable TEC of titanium and wide sintering windows. Although most preparations were more bioactive compared with those of Saiz and Tomsia–not all preparations were bioactive. Some coatings were biocompatible with fibroblasts, but not osteoblast-like cells. Whilst some glasses might not be suitable for a coating, they may have use as structural scaffolds for skeletal reconstruction.

The initial phase of this study was to develop a force transducer to investigate occlusal forces during the process of mastication. The strain gauge transducer was designed to attach to an Astra implant. A commercial pressure transducer was also used under one distal saddle of the denture. The calibration method was designed to record unilateral masticatory forces regardless of the site of loading. Five edentulous subjects with implant stabilised mandibular overdentures and maxillary complete dentures were selected for the study. Mandibular movements and unilateral Masseter muscle EMG were recorded. Experiments were designed to establish within subject differences related to cycle type, food type, EMG-force relationship, chewing side and cycle phase. Maximum biting force on a bite gauge and in the intercuspal position were also recorded. Details of force production during the closing and occlusal phases improved the description of the movement cycle and it's relationship to food breakdown. A classification of chewing cycles is proposed based on the force exerted in the closing and occlusal phases. This provides objective criteria for separating crushing, reduction and mush cycles. Peak forces varied between subjects, but are characteristic for the type of food within subjects. The different strategies used by subjects appeared to be partly related to the force capacity of the individual. The duration of force in the closing phase was related to the stage in the chewing sequence and indicated the degree of bolus resistance. A longer force duration in the closing phase was usually accompanied by a shorter occlusal duration and consequently an early occurrence of force peak relative to occlusion. The progressive change of jaw gap at the beginning of force was consistent with the expected reduction of particles through the masticatory sequence. The jaw gape at maximum velocity correlated with maximum jaw gape but both did not decrease progressively 2 Abstract through chewing sequences. Conversely, the jaw gape at which force exceeded 5N showed patterns of progressive decrease especially with frangible foods. Integrated force and Emg showed high correlations during mastication, better than peak values. These correlations were, however, weaker than those found in static unilateral biting. The slope difference found between the two conditions contraindicate the use of Emg activity in static unilateral biting as an index for measuring masticatory forces. This study has, thus, validated a method for investigating masticatory forces and shown their value for analysis of dynamic aspects of the loads that occurs during mastication.

Background: Oral submucous fibrosis (OSMF) is a pre-neoplastic condition, causally linked to areca nut consumption, the pathogenesis of which is poorly understood. TGF-β and disturbances in the balance between MMPs and TIMPs have been implicated in increased collagen deposition and fibrosis but no previous study has addressed the role of mesenchymal senescence in OSMF. Materials & Methods: Senescence and its secretome, DNA damage, oxidative damage, ROS production and mitochondrial damage were studied in OSMF in vivo and in vitro using ELISA, immunofluorescence, western blot and FACS techniques. Results: Senescent cells increased in all OSMF samples (1.9±0.3; p=0.004) peaking when dysplasia was present in the OSMF epithelium. There was increased oxidative damage (6.7±1.8; p=0.004); elevated DSBs (10.4±1.1; p=0.004) and P16ink4a accumulation (4.2±1.7; p=0.004). The results were similar in vitro. The OSMF fibroblasts demonstrated a reduced replicative lifespan (MPD-22±7.2; p=0.0001), despite having normal telomere lengths and in vivo growth rates. However, the OSMF fibroblasts showed increased ROS production and increased mitochondrial density and hyperpolarization, suggesting mitochondrial damage. The antioxidant, N-tert-Butyl-α- phenylnitrone (PBN) reduced the frequency of senescent fibroblasts and their associated markers in both OSMF and the control cultures. The mild uncoupling of mitochondrial oxidative phosphorylation from ROS generation with dinitrophenol (DNP) gave similar results. Cytokine profiles from cells obtained from OSMF showed a significant elevation of TIMP-1 (2217.4±406.5; p=0.003) and TIMP-2 (1763.2+/-363.7 pg/ml; p=0.004) production as compared to normal. The levels of MMP-1 (7.0±2.2 ng/ml; p=0.30), MMP-2 (157.8±91.3 ng/ml; p=0.75) and TGF-β1 (389.5±250.6 ng/ml; p=0.22) were not different to the normal and non-diseased controls (ND) collagen production was not elevated in OSMF in vitro (20.6±4.4 μg/ml; p=0.22). 3 Conclusion: Senescence, DNA damage, oxidative damage and P16inka accumulation are associated with neoplastic progression of OSMF. Elevated TIMP levels did not result in increased collagen secretion but may be an early marker of fibroblast aging and senescence.

Identification of the most representative location for biopsy is critical in establishing the definitive diagnosis of oral mucosal lesions. Currently, this process involves visual evaluation of the colour characteristics of tissue aided by topical application of contrast enhancing agents. Although, this approach is widely practiced, it remains limited by its lack of objectivity in identifying and delineating suspicious areas for biopsy. To overcome this drawback there is a need to introduce a technique that would provide macroscopic guidance based on microscopic imaging and analysis. Optical Coherence Tomography is an emerging high resolution biomedical imaging modality that can potentially be used as an in vivo tool for selection of the most appropriate site for biopsy. This thesis investigates the use of OCT for qualitative and quantitative mapping of oral mucosal lesions. Feasibility studies were performed on patient biopsy samples prior to histopathological processing using a commercial OCT microscope. Qualitative imaging results examining a variety of normal, benign, inflammatory and premalignant lesions of the oral mucosa will be presented. Furthermore, the identification and utilisation of a common quantifiable parameter in OCT and histology of images of normal and dysplastic oral epithelium will be explored thus ensuring objective and reproducible mapping of the progression of oral carcinogenesis. Finally, the selection of the most representative biopsy site of oral epithelial dysplasia would be investigated using a novel approach, scattering attenuation microscopy. It is hoped this approach may help convey more clinical meaning than the conventional visualisation of OCT images.

The aim of this study was to describe the average age of permanent mandibular tooth formation in two groups of Sudanese children using a cross-sectional design following STROBE guidelines. The Northern groups are of Arab origin whilst the Western groups are predominantly Fur of African origin (Darfur). North Sudanese sample (844 males, 802 females) consisted of equally distributed, randomly selected healthy university students and school children, whilst the West Sudanese (848 males, 401 females) consisted of a convenience sample attending religious schools in camps for the internally displaced. Panoramic radiographs (2-23 years), with known date of birth were taken. Height and weight were also measured. Developing permanent mandibular teeth were staged from radiographs (Moorrees et al., 1963). The mean age of attainments were calculated using logistic regression and comparisons carried out on 331 tooth stages to determine gender and ethnic differences. Results showed that mean age of attainment of teeth was not significantly different between the genders within each ethnic group (p>0.05) for 135 out of 155 stage comparisons. The mean age of attainment of teeth was not significantly different between same sex groups in 113 out of 174 stage comparisons (p>0.05). The canine was more advanced in females compared to males while the reverse was true for some crown and root stages of third molars. Growth indicators showed that all groups are undernourished (z-scores =< -2). Severe malnutrition had minimal effect on tooth formation of M1 and M2 (p>0.05) in Northern females. The prevalence of hypodontia (excluding third molars) was 0.7% in the Western group and 2.6% in the Northern group. The pattern of hypodontia differed between groups. In conclusion, the within group variation for most tooth stages is considerable while the differences between groups are small. The study represents the first radiographic investigation of permanent tooth formation in Africa.

Health inequality according to socioeconomic status has been established. There is evidence for inequality for self-reported oral health outcomes. There has been interest in exploring the factors that explain general health inequality such as health behaviours and psychological factors. However, few studies have examined whether oral health behaviours and psychological factors explain oral health inequality among adults from industrialised countries. The aim of this thesis is to investigate whether oral health behaviours and psychological factors explain inequality in self-reported oral health among Iranian adolescents. This study tested four conditions according to the hypothesis of mediation; the final condition is that adjusting for the mediating factors attenuates the relationship between socioeconomic status and oral health. A questionnaire was used to collect data on four sets of variables from 639 males and females aged 15-17 studying at secondary schools in Sanandaj, Iran: socioeconomic status, oral health behaviours, psychological factors, and self-reported oral health outcomes. Indicators of socioeconomic status were subjective socioeconomic status, wealth index, mother‟s education and father‟s education. Oral health behaviours were toothbrushing, dental flossing, and visiting dentist. Psychological factors were selfesteem, depression, and anxiety. Self-reported oral health outcomes were single item self-rated oral health, and the experience of dental pain. Several regression models were conducted to examine the four conditions of the hypothesis of mediation. This study found a graded relationship between indicators of socioeconomic status and self-reported oral health outcomes, but no strong evidence to support the hypothesis that oral health behaviours and psychological factors mediate oral health inequality for self-reported oral health outcomes. Adjustment for oral health behaviours and psychological factors led to only small changes in the associations between socioeconomic status and self-reported oral health outcomes. In conclusion, oral health behaviours and psychological factors explained a little extent of oral health inequality for self-reported oral health outcomes.

The remaining debris and biofilm in the anatomical complexities of root canal systems can affect treatment outcomes. Files with asymmetric cross-section design may improve debris and biofilm removal from these difficult spaces during canal preparation. Tooth opacity and different densities of the remaining materials prevent the direct systematic assessment of the preparation process. The present study assessed remaining debris and biofilm using a novel transparent root canal model with novel approaches. Natural and simulated root canal samples with isthmus space were evaluated. Canal preparation by ProTaper Next and Revo-S asymmetric systems was evaluated in comparison to the standard ProTaper Universal symmetric system. The root canals were investigated by microcomputed tomography (micro-CTL confocal laser scanning microscopy (CLSML and optical coherence tomography (OCT))) imaging tools. Data analysis was undertaken with SPSS (V. 24). Files with asymmetric cross-section and constant taper removed more debris and biofilm from the complex root canal system. The model allowed direct assessment of remaining materials and confirmed the novel imaging approach with the OCT. In conclusion, the asymmetric design improves debris and biofilm removal especially when used with a constant taper. The model was verified as an ideal system for assessing root canal treatment in vitro.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that affects about 1% of the world population. This common disease is characterized by chronic inflammation of the synovium that leads to destruction of cartilage and bone in the join, and the cause of this exacerbated inflammatory reaction remains unknown. Periodontitis (PD) is also a chronic inflammatory disease characterized by destruction of bone and other connective tissue that shares notable similarities with RA. Over the last 20 years, numerous studies have found an epidemiological connection between RA and periodontitis. However the biological mechanisms that explain the interrelations between the two conditions are not known. The aim of this thesis was to investigate the role of periodontitis in RA and the effect of periodontal therapy on immunological and microbiological parameters. To do that, different biological samples were collected from two pilot studies, comparing RA and periodontitis patients to the appropriate controls and from a selected group of randomized RAPD patients before and after periodontal therapy. The antibody response and subgingival microbiome of patients with RA and periodontitis were compared to the appropriate controls (no RA no PD, RA no PD, no RA PD). The effect of periodontal therapy on these parameters and on the cytokine changes in gingival crevicular fluid was also investigated. The findings from this thesis lend further credence to the link between RA and the oral microbiome, with RA patients having a disrupted and more anaerobic microflora and an exacerbated immunological reaction against periodontal bacteria and citrullinated proteins.

Dental Health Care has been provided by the Grenfell Association for the people of Northern Newfoundland and Labrador since the late 1800's. The capability to provide dental care has been influenced by many factors including a small population living in isolated communities over an enormous geographical area with adverse climatic conditions and long lines of communication. Transportation alone presented a formidable challenge. Based on his early experience with the Association between 1964-69, the author realised, on his return to Canada in 1976 that there was need to identify major problems, adapt existing facilities and change established philosophies, as well as to introduce new systems and methods to improve dental health-care delivery. The main areas of concern were the high prevalence of dental disease, the lack of adequate manpower, appalling working conditions and lack of overall policies. Initially, one of the major tasks was to establish basic equipment at each clinic. Small portable light-weight dental units were designed and constructed by the author, for each dentist with a travelling commitment, these units being readily connected to on-site compressors. Thereafter, a longterm policy of equipment upgrading and replacement was pursued to enable dental staff to undertake a complete range of clinical duties. Later, when new Health Centres and Nursing Stations were established, the author had the opportunity to become involved in their design and layout. The method of dental service financing also contributed to many of the problems. Thus the existing monetary arrangements had to be studied which, in turn, required an understanding of the sources of funding. Hence, following analysis of financial data collected after only the first few months of 1976, it became clear that several issues required urgent action and, as monetary considerations appeared to be the crux or the problem, the author decided to introduce a standard billing system which was applied throughout the region. This was primarily operated by dental assistants to provide continuity between dental staff changes. To reduce financial hardship, fee increases to conform with general dental fees charged elsewhere in Newfoundland were introduced gradually over a five year period. When sufficient data on the work being undertaken via the Provincial Dental Programme became available, Department of Health funding was evaluated. This led to a report and submission to the Department of Health in 1977, which was intended to exert pressure for fairer remuneration of the Grenfell Dental Service. The effect of the measures taken by the author to increase manpower, improve facilities, reduce caries prevalence, introduce preventive measures and modify unfavourable treatment patterns has been evaluated continuously throughout his tenure as Co-ordinator and subsequently as Chief of Dental Services. The establishment of administrative pathways and centralised procedures has also provided evidence of change. In addition, further recommendations regarding future priorities have been formulated to ensure continuous staff recruitment and supporting facilities required to achieve the W.H.O. dental goals set for the year 2000. Happily, with 10 years of the Century remaining, a further mean DMFT reduction of only 0.82 per child is now required to meet the target of 3.0 for 12-yr-olds.

As the proportion of adults aged 65 years and older continues to grow across the globe and edentulism rates decline, there is widespread concern about a rise in the prevalence of periodontal disease, characterized by chronic inflammation of tooth-supporting tissues induced by persistent infection. Compared to their younger counterparts, older adults experience a higher burden of periodontal disease, which can result in tooth loss, poor nutritional intake, higher prevalence of other chronic diseases, and a decrease in overall quality of life. While cross-sectional studies have underscored the role of chronic stress on periodontal disease progression in older adults, longitudinal evidence is currently lacking. This dissertation draws on prospective data from a birth cohort of older Danish adults (1914 Glostrup Aging Study) with 25 years of follow-up. Using physiological markers than span the metabolic, inflammatory, and cardiovascular systems, I developed a composite measure of allostatic load (AL) at age 80, defined as the cumulative biological damage that results from a whole-body adaptation to chronic stress. First, I identified social and behavioral predictors of high scores on AL. In men, those with no vocational training, unskilled occupation, low income, and a sedentary lifestyle were more likely to have high AL, consistent with a "weathering" pattern of biological systems resulting from chronic adversity over the life course. To test the hypothesis that high AL is longitudinally associated with periodontal disease, I evaluated bidirectional longitudinal associations using multiple measures of AL and periodontal disease. Results showed a positive nonlinear association of AL at age 70 with periodontal disease at age 85, but no association between periodontal disease at age 70 with AL at age 80. This finding confirms previous cross-sectional data, and supports the role of chronic stress on infection-induced inflammation. To test the hypothesis that high AL is associated with mortality risk, I examined this association longitudinally from ages 70 - 95. Compared to low AL, high AL was positively associated with all-cause mortality, and even stronger when cardiovascular disease mortality was considered. AL-mortality associations were higher among those who were dentate as compared to edentate, suggesting that dentate status modifies the relationship. Findings from this dissertation contribute to our understanding of the consequences of stress on periodontal disease in relation to aging and offer potential avenues for intervention.