Fibre-reinforced dental resin composites (FRCs) have shown increased fracture resistance and tensile strength compared with particulate filled composites (PFC). However, clinically successful restorative materials require adequate bond strength and wear resistance along with high strength. An experimental FRC (ST) was developed and tested as a dentine replacement. It has randomly distributed E-glass fibres above their critical length of 0.5-1.6 mm. This work aimed to evaluate the possibility of using ST as a single restorative material by assessing its three-body wear resistance and surface contact fatigue. The polymerisation shrinkage, water sorption, and bond strength of ST were also assessed. Two commercially available materials; an FRC (Build It FR) and PFC (Z250) were used as comparators. ST showed significantly lower wear resistance and higher contact fatigue. No significant difference was found regarding polymerisation shrinkage but ST had significantly higher water sorption, lower shear bond strength (SBS) to human dentine. SBS of the interfacial layers within and between the dental resin composites was evaluated after 24 hours and 1 year of water storage in the absence of an oxygen inhibition layer. Build It/Z250 showed a significantly higher SBS at both time intervals. The presence of an oxygen inhibited layer increased the interfacial strength in all groups except ST/Z250. ST formulations were varied in resin/diluent (Bis-GMA/TEGDMA) ratios, filler loading and fibre lengths for development. Wear testing found changing the Bis-GMA/TEGDMA ratio from 60/40 to 70/30 decreased the wear resistance regardless of filler loading and fibre length. In summary, wear resistance of ST and its variants was insufficient to recommend its use as a single restorative material without a surface veneer of PFC. As a dentine replacement, ST was only comparable with Z250 and Build It in polymerisation shrinkage and SBS between composites in the absence of an oxygen inhibition layer.

Clinical research should aim to broaden and translate the understanding of health and disease by designing and successfully implementing interventions to achieve healthcare improvement. This thesis reports clinical research that moves from laboratory to clinic and investigates the potential challenges of dissemination and adoption into clinical practice. Initially an established gingivitis was used as a model to evaluate a personalised plaque control intervention. The evaluation used traditional clinical monitoring techniques and pioneering laboratory technologies. Subsequently the personalised plaque control intervention was developed further and applied to a new clinical situation, the gingival manifestations of oral lichen planus. The personalised plaque control intervention was then evaluated as part of a randomised controlled trial using traditional clinically observed, patient-centred and health-economic outcome measures. Finally, a qualitative study investigated the potential barriers in disseminating research through continuing education to general dental practitioners. The research findings showed that in the established gingivitis model, sequential plaque control interventions, comprising powered toothbrushing and professional prophylaxis, were effective in reducing the clinical signs of established gingivitis. Changes in clinical signs were associated with a shift in bacterial species, and transient changes were observed in host inflammatory biomarker concentrations. Personalised plaque control was cost-effective and reduced clinical signs of inflammation and brought about improvements in quality of life for patients with gingival manifestations of oral lichen planus. The qualitative study identified barriers to the successful translation and implementation of contemporary clinical research. The plaque control intervention evaluated in the established gingivitis model and successfully implemented in a new clinical situation. Personalised plaque control should form part of the initial management phase for patients with gingival manifestations of oral lichen planus. Researchers should investigate alternative methods for engaging with general dental practitioners in disseminating research to ensure that relevant findings are translated into improvements in healthcare.

This thesis describes a series of investigations into the effects of root canal irrigants on dental root dentine. Imaging of human, ovine and bovine root dentine revealed no significant differences in tubule density or diameter. Canal volumes were estimated to be significantly different between human and bovine, but not between human and ovine teeth. EDAX identified significant differences in Ca/P ratios between ovine and bovine, and between ovine and human dentine at points up to 300μm from the root canal lumen. The Ca/P ratio of bovine dentine was significantly lower than human at the canal lumen only. Atomic Force Microscopy (AFM) revealed human and bovine root dentine to be significantly stiffer than ovine dentine at all depths from the canal lumen; human root dentine was stiffer than bovine dentine up to 300μm from the lumen. Animal teeth were concluded to be imperfect replacements for human teeth in endodontic research. Serial polishing down to 0.05μm aluminium oxide was refined for the gentle removal of laboratory-generated smear layers from sectioned dentine specimens, allowing analysis of subtle surface and sub-surface changes following exposure to root canal irrigants, and AFM analysis of smooth, flat dentine surfaces. A new 5-point scale was developed for scoring root canal cleanliness. NaOCl (5% & 10%) removed pulpal debris and predentine from canal walls after 5 minutes exposure at room temperature, with no evidence of chemical etching (score 4). NaOCl (2.5%) also resulted in a score of 4 in the coronal third, although in middle and apical thirds it was less effective (score 3). AFM analysis revealed no change in surface or sub-surface dentine stiffness after exposure to NaOCl, (5% & 10%, 5 minutes). Significant changes in dentine stiffness after exposure to 17% EDTA and 6% citric acid for 1 minute, were not increased after 2 minutes exposure.

This thesis examines psychosocial issues experienced by participants following a diagnosis of facial malignancy and ablative cancer surgery of the face. It investigates how participants felt about surgery and the affect that the use of postoperative facial prostheses had on each participant. Semi-structured interviews were used to capture participants' experiences of treatment. Interpretative Phenomenological Analysis (Smith 2004; Smith, Flowers & Larkin 2009) was used to perform a content analysis of the data which revealed themes and sub-themes common to all participants. Ethical approval was granted for the inclusion of up to eight participants in the study. Initially twenty participants were randomly selected and contacted by letter. Thirteen individuals agreed to their inclusion in the study and eight were randomly selected for inclusion and contacted by letter. The five individuals not selected were contacted and thanked. Interviewing ceased after the sixth participant had been interviewed n=6 after no new themes relative to the study were discovered. Some findings of the research were congruent with previous research. A supportive partner and family group make coping easier. Professional attendants who listen and allow individuals to talk have a positive impact. Findings specific to this study suggest that facial prostheses are useful after ablative cancer surgery of the face. Prostheses restore outward normality which was important for reasons of social acceptability. However, the study found that feelings of normality were not restored This concluded with a re-definition of normality for disfigured patients who use a facial prosthesis to incorporate the wider context revealed by the study.

The success of root canal treatment is dependent on canal debridement, disinfection and impervious obturation of the root canal system. The material most commonly used for root canal obturation is the trans-isomer of isoprene, known as gutta-percha. Limitations of gutta-percha as a root canal obturation material include lack of flexibility and potential for degradation caused by eugenol or other components of root canal sealers and restorative materials. A detailed study on the development, characterisation and in vitro evaluation of a composite, tailor-made to function as a root canal obturation material as well as serve as a “carrier” for delivering a root canal obturation material was undertaken. Polymer composites comprising of low density polyethylene (LDPE), hydroxyapatite (HA) or 45S5 Bioglass® (BAG) and strontium oxide (SrO) were developed via extrusion using a single screw extruder and drawn into the desired shape using appropriate ‘dies’ and optimised based on their physical and mechanical properties. The polyethylene in the composite showed no evidence of degradation post extrusion as confirmed by FTIR spectroscopy, the thermal analysis showed that the HA/PE composites had melting point of 110.5-111.2°C, much higher than that of gutta-percha (52°C). The tensile strength and elastic modulus of the silanated HA/PE composites were significantly higher than those of gutta-percha (p<0.0001) under dry conditions and after storage in simulated body fluid. Furthermore, the interaction of eugenol did not produce any change in the experimental HA/PE composites whereas gutta-percha showed a significant increase in the weight. The radiological contrast of the silanated HA/PE fibres was adequate to allow their use as a root canal obturation material. Bioglass® reinforced low density polyethylene with SrO composites are promising obturation materials for endodontic treatment. They exhibited superior stiffness in comparison to gutta-percha with excellent biocompatibility and bioactivity. An enhanced proliferation of human osteoblast cells was also observed.

Chronic dental disease is associated with elevation of systemic markers of chronic inflammation that play a role in the pathogenesis of atherosclerosis and its complications. However, to date there is no evidence that invasive dental treatment may serve as a trigger for acute cardiovascular events. An understanding of the precise molecular and cellular mechanisms that underly the vascular events associated with invasive oral health care is essential to improve the dental management of patients with known CAD. This present research was intended to determine if such mechanisms were possible. Forty Five patients (36 men and 9 women) referred for dental extraction were categorized into two groups (28 with and 17 without coronary artery disease). Venous blood samples were obtained before, immediately after and 24 hours after the dental procedure. A spectrum of biomarkers were used to assess myocardial injury (highly sensitive troponin T), systemic inflammation (CRP, fibrinogen, IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α, ICAM, E-selectin and P-selectin), endothelial injury (t-PA, PAI-1, vWF and thrombomodulin), bacterial burden (LPS endotoxin), psychological stress (cortisol), cellular oxidative stress (DHR), monocyte/macrophage activation (neopterin) and thrombin generation (TGA). Dental surgery was associated with a significant rise in hs-cTnT, acute systemic inflammation, a rise in bacterial LPS endotoxin, increase in hypercoagulable state and a tendency of intracellular OxS to increase. These changes were similar in both patients with or without CAD, with the changes in systemic inflammation, LPS endotoxin and OxS being more evident in those with hs-cTnT rise. The present study is the first to demonstrate that exodontia is associated with minor myocardial injury, representing a possible link between invasive dental treatment and acute cardiovascular events. The observed molecular and cellular changes may represent the possible mechanisms by which minor myocardial injury may occur following dental surgery. If proven to be clinically significant, the present observation of an hs-cTnT rise indicates that exodontia can have a negative impact upon the management of dental patients with CAD.

The effect of some anticancer drugs can be severely reduced by entrapment of the drug molecules in intracellular acidic vesicles such as endosomes and lysosomes. Photochemical internalisation (PCI) is a novel technology for photochemical drug delivery where low doses of a photochemical treatment are employed to release entrapped drugs from such vesicles into the cytosol, from where they can reach their therapeutic target. This thesis discussed both the in vivo preclinical animal study and the first in human clinical trial of TPCS2a (Amphinex®) based PCI of bleomycin for treatment of patients with local recurrence or advanced/metastatic, cutaneous or subcutaneous malignancies. The preclinical in vivo experiments on Golden Syrian Hamsters investigated the bio-distribution of TPCS2a in normal and malignant oral tissues. The study was tested the selectivity of TPCS2a based PCI of bleomycin in the hamster cheek mucosa squamous cell carcinoma (SCC) model. The ratio of TPCS2a uptake in cancerous to normal tissue was 2:1 using fluorescence microscopy. Also, TPCS2a with PCI based bleomycin showed a selective necrotic effect on the cancerous tissues with a minor effect on the adjacent normal site, however this selectivity disappeared and tissue damage was observed on both cancerous and adjacent normal tissue when higher doses of TPCS2a or light were applied. The experiments concluded that PCI might be able to produce a selective therapeutic effect on cancer if appropriate drug and light doses used. Meanwhile, the first PCI clinical trial was undertaken to investigate the safety, pharmacokinetics (PK) of TPCS2a and the efficacy of treatment. No unexpected safety concerns were observed. The maximum tolerated dose (MTD) of TPCS2a was at 1 mg/kg. The maximum concentration of TPCS2a in blood was detected 30 minutes after administration. 0.25, 0.5, 1 and 1.5 mg/kg TPCS2a showed similar efficacy but the efficacy results of 0.125 mg/kg Amphinex® was not sufficient. This study was concluded that the treatment is safe with no reported major adverse events. The skin photosensitivity of the selected dose of TPCS2a (0.25 mg/kg) for phase II study was tolerable when the photosensitised skin was illuminated with 100.000 lux for 5 minutes. Although the study was too small to draw conclusions about the efficacy, these early results are promising and justify further studies.

Orthodontic retainers may be considered as removable implants and confer the same problems as other implants with regard to colonisation by microorganisms. Thus, biofilms forming on their surface may compromise the oral health of patients and jeopardise the efficiency of the therapy. The first part of the project involved a clinical study, a cross-sectional observational cohort, to assess the effect of orthodontic treatment on the oral microbiota and the carriage state of opportunistic pathogens during the course of treatment. High proportions of health-associated species were detected in the retainer group. However, Staphylococcus and Candida species were frequently (69% and 36% respectively) isolated from the retainers and the oral cavity of retainer wearers, where Staphylococcus spp. comprised up to 5% of the microbiota. The increase in Staphylococcus spp. including Methicillin Resistant Staphylococcus aureus (MRSA) on retainers was associated with an increase in numbers of these species on the oral mucosa of the cheek and tongue. Orthodontic retainers could, therefore, be a reservoir for pathogens and act as a source of cross-infection. A series of in vitro investigations were subsequently carried out to evaluate the effect of the surface characteristics of retainer materials, including surface roughness, hydrophobicity and surface free energy, which may affect colonisation by opportunistic pathogens. After polishing the surface of the acrylic substrata the results revealed that Atomic Force Microscope was the most appropriate device to measure the surface roughness of the acrylic and thermoplastic materials in a consistent manner. Additionally, the acid-base interactions, especially the electron donor interaction, influenced the bacterial attachment onto the thermoplastic samples. Finally, assessment of novel antimicrobial-containing acrylic resins was carried out. Firstly, incorporation of chlorhexidine showed a prolonged antimicrobial effect against MRSA but was detrimental to the mechanical properties. Thymol was successfully incorporated in heat cured acrylic materials. It reduced the surface free energy of the modified resin with no effect on the mechanical properties and was strongly antimicrobial against C. albicans. However, it showed a lesser antimicrobial effect against MRSA. This PhD has shown the potential of orthodontic retainers as reservoirs for opportunistic pathogens and that surface characteristics are significant in the retention and potential removal of these pathogens. The use of antimicrobial acrylic materials may be of potential therapeutic benefit following further development.

This thesis had as an overall aim to investigate some of the possible associations between periodontitis and diabetes mellitus. Three areas of investigations were identified: i) clinical/epidemiological ii) genetic/immunological iii) microbiological. 630 outpatients diagnosed with type 1 or type 2 diabetes were included in the first study. The periodontal health of the patients was assessed by means of the Basic Periodontal Examination. For the most advanced cases a full mouth periodontal examination was sought at a later time. The same subjects donated venous blood for genetic analysis. Single nucleotide polymorphisms associated with Interleukin-6, Interleukin-18, Chromosome 9 and FTO (Obesity gene) were analysed. The leukocyte telomere length of the same subjects was also assessed. Associations were found between some of the Interleukin-6 and Interleukin-18 polymorphisms and the presence of severe periodontitis. Also an association of the FTO gene polymorphism was found between severe periodontal disease and type 2 diabetes mellitus. Furthermore, the leukocyte telomere length of the periodontal patients was found to be significantly shorter that that of the periodontally healthy or gingivitis patients. This may be a manifestation of the systemic inflammatory burden that chronic periodontal disease constitutes. A second group of 40 type 2 diabetic patients that were receiving either subgingival debridement or minimal supragingival debridement as part of an ongoing clinical study were chosen for microbiological assessment by means of pyrosequencing at baseline and 2 months following treatment. The results showed a significant clinical improvement in a subgroup (“good responders”) accompanied with a shift of the subgingival microbial population to one more aerobic and one closer to the microbial population associated in the literature with clinical healthy periodontium. Overall several associations on clinical and genetic level were identified. Further observational and experimental studies are needed to elucidate the nature of these associations.

Glass-ionomer-cements (GIC) have been shown to act as matrices for the slow release of fluoride ions. The aim of the current research is to assess whether the incorporation of differing species leads to a similar release pattern. In this study, the objective is to attempt to clarify the release mechanism within the cement. GICs evaluated had differing glass compositions all glasses having Si Al Ca and O present. AH2 has additionally Na, F and P, MP4 had additionally Na, LG26 had additionally F and P and LG30 P only. The influence of different ions on the binding and release characteristics of the cement were evaluated. This study investigated the use of four different experimental GICs as carriers for the release of chlorhexidine acetate (CHA) and amprolium hydrochloride (AHCI) at included concentrations ranging from 0.5% to 13.0% of added species by weight. Release into water at 37 °C was examined using high-performance liquid chromatography (HPLC). Physical properties evaluated included compressive strengths, and working times and setting times. In general, the more added species that was included, the greater the amount released. More amprolium hydrochloride was released and at a faster rate than chlorhexidine acetate. For most GICs, compressive strengths were found to be decreased by the presence of an additional species, while working and setting times increased. Amprolium hydrochloride had a more marked effect than chlorhexidine acetate. The effects of included species on the surfaces of the GICs were observed by Scanning Electron Microscopy. The influences of the additional species on the chemical setting of the GICs were measured by spectroscopic methods including FTIR.