There are social gradients in general and oral health. Few studies have examined the pathways towards the gradients in oral health and compared them to the pathways suggested for general health gradients. The objectives of this thesis are: (1) to examine and compare the social gradients in selected indicators of oral and general health, (2) to examine the gradients in selected indicators of health-related behaviours, (3) to examine and compare some of the potential pathways towards the gradients in oral and general health. Data were from the Third National Health and Nutrition Examination Survey, pertaining to adults aged 17 years and over in the United States. Oral health indicators were perceived oral health, tooth loss, edentulousness, and four variables indicating periodontal disease. General health indicators were perceived general health, and ischaemic heart disease. Health-related behaviours were smoking, visits to a dentist, frequency of eating fresh fruits and vegetables, and frequency of exercise. Socioeconomic position was measured by years of education and poverty-income ratio. Regression models were conducted to assess education and income gradients in all the health outcomes and all the behaviours, and to examine the effects of certain pathways and factors on health and on the social gradients. These factors included sex, ethnicity, cognitive ability, health-related behaviours and stress (allostatic load). Changes in the social gradients in oral and general health were assessed after adjusting for these factors. There were consistent and similar social gradients in oral and general health (objective 1), consistent social gradients in some but not all health-related behaviours (objective 2), and similar pathways towards the gradients in oral and general health (objective 3). Health behaviours, tooth cleanliness, and stress appeared to be the important pathways affecting the gradients in oral and general health. In conclusion, relative poverty is an important factor that affects the social gradients in oral and general health similar pathways appear to exist for the oral and general health outcomes explored in this thesis.

Dental implants are a popular solution to missing teeth; they are predominantly formed from titanium due to its biocompatibility, corrosion resistance and high rate of osseointegration. While micro-roughening of the surfaces has been shown to increase osteoblast adhesion and proliferation, it has also been shown to increase the adhesion of bacteria and therefore the likelihood of implant infection and implant failure. Chlorhexidine is a broad spectrum antimicrobial agent used extensively in healthcare, particularly in oral care products such as mouthwash. It has previously been shown to adhere to titanium, forming a saturated surface layer within 60 s; these surfaces exhibited an antimicrobial efficacy against the oral bacterium Streptococcus gordonii. However, this effect was shown to be short-lived as the coated surfaces released their entire chlorhexidine payload within c.a. 2 days' immersion in water. The development of two surface coatings, based on nanoparticle and coacervate technology, is described in this thesis. The aim was to increase the surface retention of chlorhexidine on a titanium surface to provide antimicrobial functionality. An antimicrobial nanoparticle has been developed by combining chlorhexidine with hexametaphosphate. These particles form micron-sized surface aggregates on titanium substrates upon exposure to the nanoparticle suspension. The nanoparticle-coated titanium substrates elute soluble chlorhexidine for 230 days and exhibit an effective antimicrobial action against the oral primary coloniser S. gordonii and oral pathogen Porphyromonas gingivalis. An antimicrobial coacervate has been created through the combination of chlorhexidine and carboxymethyl dextran. When this suspension was drop-cast onto a titanium surface, a confluent film was formed; these film-coated surfaces exhibited an antimicrobial efficacy against S. gordonii. The film was released from the surface after immersion in water for 1 hour. Finally, by applying both coatings, a dual-action antimicrobial surface has been developed

Extrinsic staining of teeth is a common aesthetic problem for which toothpaste manufacturers strive to produce effective products to chemically and/or physically control the problem. Clinical studies proving efficacy are rare and reliance on tests in vitro are more common. The aim of these studies was to develop two in vitro models which could be used to screen and compare agents and formulations for dietary stain control. The first model utilised immobilised hydroxyapatite (RA) with tea as the chromogen. Using residual tea optical density to assess extrinsic staining proved unreliable. Tea extraction and direct measurement from wells however was shown to be reliable in demonstrating the efficacy of known active chemical agents and differentiating between toothpastes. The second model used roughened Perspex to simultaneously assess toothpastes and their ingredients for chemical and or mechanical stain removal. In line with the RA model, results differentiated between toothpastes and other agents for chemical stain removal. Chemical/mechanical stain removal in the model also showed differences for toothpastes, abrasives and detergents but abrasivity levels did not show the expected linear correlation: the toothbrush itself appeared to be the dominant factor in the model. The final experiment attempted to determine whether chromogen/pellicle interaction was specific or non-specific. Results showed no evidence of specificity indeed data suggested that chromogens may merely be absorbed into the pellicle and held physically rather than by chemical interactions. Since some of the data from both models was consistent with other published laboratory and clinical studies it is cautiously concluded that the models may prove rapid, simple and useful screening methods for anti-staining agents and products. Only the availability of more clinical data to support claims for numerous products, however, will allow the models to be retrospectively validated.

Background: Primary tooth eruption is a complex and highly regulated process through which primary teeth enter the mouth and become visible. Along with many other aspects of development, genes are thought to explain a large proportion of the variation in primary tooth eruption, although environmental factors are also thought to contribute. The aim of this thesis was to investigate the genetic and environmental determinants of primary tooth eruption. Methods: The majority of analyses carried out in this thesis were based on data collected from the Avon Longitudinal Study of Parents and Children (ALSPAC). Initially a series of observational analyses were conducted to examine the relationship between several early life exposures and primary tooth eruption (assessed at 15 months) in 7,445 individuals from ALSPAC. I then examined whether primary tooth eruption was related to future anthropometric measures in a longitudinal sample of 2,977 individuals at 17 years. In order to identify genetic variants involved in primary tooth eruption I performed a population based genome-wide association (GWA) meta-analysis of 'age at first tooth' and 'number of teeth' using 5,998 and 6,609 individuals respectively from ALSPAC and 5, 120 and 4,904 individuals respectively from the 1966 Northern Finland Birth Cohort (NFBC 1966). Finally, I examined whether the relationships previously established between primary tooth eruption and anthropometric measures at adolescence were a consequence of genetic and/or environmental factors, by carrying out a series of analyses using allelic scores and Genetic Complex Trait Analysis (GCTA). Results: Several early life factors were associated with primary tooth eruption including birth weight, breastfeeding and maternal smoking, which failed to attenuate after adjustment for confounding (including patiner smoking). 'Number of teeth' was positively associated with height (males only), weight and fat mass at 17 years in fully adjusted models. In genetic analyses, 15 independent loci (including 8 novel variants) were associated with primary tooth eruption (p<5xlO-8 ) . These loci overlapped genes previously implicated in tooth development, generalised growth and/or cancer. Together these variants explained approximately 6.1 % of the variation in 'age of first tooth' and 4.8% of the variation in 'number of teeth'. There was little evidence to suggest that variants associated with tooth eruption at genome-wide significant levels had pleiotropic effects on height, weight, fat mass or lean mass. However, several previously robustly associated height SNPs were also associated with primary tooth eruption. Bivariate GCT A analyses provided fm1her evidence for this relationship through the estimation of a negative genetic correlation between 'age at first tooth' and height. Conclusions: Several early life factors were related to primary tooth eruption. The association between maternal smoking during pregnancy and primary tooth eruption was consistent with an intrauterine effect. Primary tooth eruption was also associated with future anthropometric measures of growth and development, with early eruption related to the development of adiposity in later life. GCTA and genetic association analyses identified several novel genetic variants associated with primary tooth eruption and suggest that at least pa11 of the relationship between eruption and anthropometric measures at later ages is a result of genetic factors.

The effect of trace elements such as fluoride on multi-factorial tooth wear is poorly understood. This study examined the role of varying fluoride compounds and products in multi-factorial tooth wear models. Dedicated software for surface profile measurement of dental hard tissues using white light confocal profilometry was developed and a measurement uncertainty evaluation completed. Microhardness techniques were validated and the remineralisation protocol developed. Human teeth were donated in line with research ethics and enamel and dentine samples were prepared. A series of three distinct experiments involving varying fluoride preparations and concentrations were completed. Firstly, the effect of an aqueous sodium fluoride solution of increasing concentration on citric acid erosion and attrition of enamel and dentine was investigated. 5000 ppm and 19000 ppm sodium fluoride solutions significantly reduced enamel loss versus control after 15 cycles of erosion-attrition, however no other groups showed significant differences. Secondly, the effect of a single application of highly concentrated sodium fluoride, stannous fluoride and titanium fluoride solutions and a sodium fluoride/calcium fluoride varnish on hydrochloric acid erosion and tooth brush abrasion of enamel was investigated. The titanium fluoride solution and the sodium/calcium fluoride varnish reduced enamel loss significantly after erosion, however, in the erosion-abrasion protocol only the sodium fluoride solution and the sodium/calcium fluoride varnish showed a statistically significant reduction in enamel loss after 15 cycles. Chemical and ultra-structural analyses supported these findings. Finally, the effect of a single application of two highly concentrated sodium fluoride varnishes and a fluoride-free self-etch adhesive on citric acid erosion and attrition of enamel was investigated. Both fluoride varnishes resulted in statistically significant reductions of enamel loss versus the self-etch adhesive and the negative control, at all stages of the study. Overall, these studies showed potential for highly concentrated fluoride preparations to provide protection against erosionabrasion and erosion-attrition in vitro.

Dental pain is a very common ailment affecting a large percentage of people and its mechanisms are not well understood, thus impairing the development of new therapies. The current paradigm of dental pain is that thermal or osmotic changes around a tooth produce movements within the dentine fluid, which are detected through mechanoreceptors on dental sensory neurons. However, initial studies have identified tentative links between TRP channels and dental pain, suggesting that TRP channels in dental nociceptive neurons may be directly activated by temperature changes and contribute to sensitivity to hot or cold foods. Certain structural and biochemical properties of odontoblasts suggest that they may also play a role in pain sensation. The aim of this project was to investigate the expression of pain-related ion channels (TRP channels) in human pulp cells (odontoblasts). Dental pulp cells were isolated and cultured in conditioned medium to allow for differentiation following which they were characterized by demonstrating the expression of odontoblast phenotypic markers. This cell culture model was optimized and a viable immortalised cell line established, and then used to determine the responsiveness of these odontoblast-like cells to TRP channel agonists and antagonists following the identification of their expression. The data obtained from this study will serve as a template for the better understanding of the function of TRP channels in human odontoblasts.

The first section of this work is a review of the literature necessary to understand the objectives of the project; it includes general information about dental adhesive technology as well as adhesion testing, about dentine hybridisation and about the drawbacks of contemporary bonding systems. Several studies revealed excellent immediate and short-term bonding effectiveness of etch-and-rinse adhesives, yet substantial reductions in resin- dentine bond strength occur after ageing. Degenerative phenomena involve hydrolysis of suboptimally polymerised hydrophilic resin components and degradation of mineral-deprived water-rich resin-sparse collagen matrices by matrix metalloproteinases and cysteine cathepsins. Silicate compounds, including calcium/sodium phosphosilicates, such as commercially available bioactive glass, and calcium-silicate Portland-derived cements are known to promote the formation of apatite in aqueous environments that contain calcium and phosphate (e.g. saliva); thus, we have raised questions about whether their presence at the bonded interface could increase the in vitro durability of resin-dentine bonds through crystal formation and self-sealing, in the presence of phosphate buffered saline or simulated body fluid solutions. In answering these questions, the objectives were accomplished by employing Bioglass® 45S5 in etch-and-rinse bonding procedures either (i) included within the composition of a resin adhesive as a tailored micro-filler, or (ii) applied directly onto acid-etched wetted dentine. Alternative light-curable methacrylate-based agents containing (iii) three modified calcium-silicates derived from ordinary Portland cement were also tested. Confirming the relative success of bioactive materials incorporated in the dentine bonding procedures required assessment of the potential to reduce nano-leakage, as well as their effect upon the strength of the bond over time. In order to explore these possibilities, which have not been previously investigated, a combination of methods were applied in the second experimental section. Bond strength variations were quantified using the microtensile test while scanning electron microscopy, confocal laser scanning microscopy and Knoop micro-indentation analysis were used to evaluate optically and mechanically adjustments to mineral and water content within the resin bonded-dentine interface. Initially, high microtensile values were achieved in each tested group. All the resin-dentine interfaces created with bonding agents containing micro-fillers showed an evident reduction of nano-leakage and mineral deposition after the ageing period. However, only adhesive systems containing Bioglass and two modified Portland cement-based micro- fillers were found to reduce nano-leakage with no negative effects on bond strength. Furthermore, specimens created with the same experimental adhesives did not restore micro-hardness to the level of sound dentine but were able to maintain statistically unaltered Knoop values. The second section is also composed of a set of preliminary studies that involved the use of up-to-date spectroscopic (attenuated total reflection Fourier transform infrared spectroscopy) and thermoanalytical (differential scanning calorimetry) techniques to predict the chemical-physical properties and apatite- forming ability of the novel ion-leachable hybrid materials. Lastly, the overall conclusions of the present work and directions for future research are discussed.

A series of 5 investigations assessed the application of cone beam computed tomography (CBCT) for the management of endodontic problems. Cone beam computed tomography improved the detection of the presence and absence of simulated periapical lesions in human dry mandibles. The overall sensitivity was 0.248 and 1.0 for periapical radiography and CBCT respectively. The receiver operating characteristics (ROC) area under the curve (AUC) values were 0.791 and 1.000 for intraoral radiography and CBCT, respectively. There was no improvement in the detection of artificially created vertical root fractures (VRF) in root treated teeth using CBCT compared with periapical radiographs. The overall AUC value of incomplete and complete VRF was 0.53 for periapical radiography and 0.45 for CBCT (p=0.034). The overall sensitivity of periapical radiography (0.05) was lower than CBCT (0.57) regardless of the extent of the VRF (p=0.027). Periapical radiographs (0.98) had a higher overall specificity than CBCT (0.34), (p=0.027). The prevalence of periapical radiolucencies of 273 individual roots in 151 teeth viewed with CBCT (48%) of teeth treatment planned for endodontic treatment was significantly higher when compared with periapical radiographs (20%). Periapical radiographs and CBCT scans of 123 of the teeth in 99 patients assessed 1 year after completion of primary root canal treatment were compared to their respective pre-treatment periapical radiographs and CBCT scans. Analysis by tooth revealed that the ’healed’ rate (absence of periapical radiolucency) was 87% using periapical radiographs and 62.5% using CBCT (p<0.001). This increased to 95.1% and 84.7% respectively when the ’healing’group (reduced size of periapical radioiUcency) was included (p<0.002). Outcome diagnosis of teeth showed a statistically significant difference between systems (p<0.001). The influence of periapical radiography and CBCT for the detection and management of in-vivo root resorption lesions was assessed. Periapical radiography ROC ADC values were 0.780 and 0.830 for diagnostic accuracy of internal and external cervical resorption respectively. The CBCT ROC AUC values were 1.000 for both internal and external cervical resorption. There was a significantly higher prevalence (p=0.028) for the correct treatment option being chosen with CBCT compared with intraoral radiographs. These investigations demonstrated that CBCT is more effective in diagnosis ex vivo and in vivo periapical radiolucencies, and for the diagnosis and management of root resorption. However, CBCT did not improve the detection of VRF in this experimental model.

Dentine hypersensitivity (DH) affects up to 57% of patients following exposure of unoccluded dentine tubules. However the aetiology is incompletely understood. These studies investigated the association of DH to tooth wear. A prevalence study investigated risk factors associated with tooth wear and DH on all tooth surfaces in 350 subjects aged 18-35 in SE England. Sextant cumulative scores for DH and tooth wear were validated and positive correlations existed between both (p < 0.0001). Two randomised, single blind in situ studies investigated the degree of dentine tubule occlusion provided by desensitising dentifrices following four days of twice daily brushing with agitated acid challenges on days three and four. In the first in situ study involving 28 healthy subjects, samples were imaged daily using Scanning Electron Microscopy (SEM) and graded using a ‘standard’ visual ordinal scale. On days one and two, an 8% strontium acetate and 8% arginine based desensitising dentifrice demonstrated more occlusion than control paste (p < 0.0001) and water (p < 0.0001, p = 0.0003). On day four, strontium demonstrated more occlusion than all other treatments (p < 0.0001). In a second in situ study involving 30 subjects, an innovative computerised and imaging method was created and validated to quantify tubule occlusion. Samples were imaged with Tandem Scanning Microscopy (TSM) and then SEM. Intra-class correlation of the number of un-occluded tubules counted visually and then by the computational analysis on 10% (n = 47) randomised SEM or TSM images was > 0.8. Positive Spearman correlations existed between the visual ordinal ‘standard’ and the SEM (r = 0.58) and TSM (r = 0.42) computational analyses (p < 0.001, n = 469). At day four, the TSM computational analysis and the ‘standard’ showed that an experimental dentifrice containing 5% calcium sodium phosphosilicate produced more occlusion than controls (p < 0.0001). These studies refute the null hypothesis that there is no association between DH, tooth wear and the patency of the dentine tubules. Accurate techniques were developed to measure DH.

Background: in 1970’s the seminal work of Cohen and Jago initiated an interest in the measurement of health related quality of life measures in dentistry. Clinical measures to assess oral health from the dentist’s perspective do not necessarily measure well-being. The patient reported outcome measures are an important tool to measure and improve the quality of care. Aim: The aim of the project was to create and validate a brief instrument for measuring patient-based oral health outcomes associated with endodontic care. Method: Based on the literature review of the currently used core oral health outcome measures, items from established instruments were selected to generate pool of items for the new measure. All subjects attending primary dental care at a local dental teaching hospital specifically for endodontic treatment provided by undergraduates self-completed this outcome measure prior to, immediately following care and at one month follow-up visit. Using multicollinearity, factor analysis, regression modelling and an expert based approach items were identified for a brief instrument. The newly developed brief instrument was tested for its reliability, validity and responsiveness on patients attending for endodontic treatment in the same clinical setting using the self-completed questionnaire at the baseline and after completion of the treatment. Results: 46 Items from OHIP-49 (Oral Health Impact Profile) and 12 items from GOHAI (General Oral Health Assessment Index) were used as the basis for development of an endodontic outcome measure. Multicollinearity, factor analysis and regression analysis of the long-form of the instrument (58 items) identified 15 significant items associated with improved oral health.