Outcomes of Periodontal Treatment in Patients with Rheumatoid Arthritis (OPERA) was a pilot randomized controlled trial (RCT) that aimed to assess the feasibility for a larger, multi-center RCT which would investigate the efficiency of non-surgical periodontal treatment in reducing disease activity levels in patients with rheumatoid arthritis (RA). The OPERA trial used a mixed methods approach. The quantitative approach delivered pilot data regarding the clinical outcomes of the intervention, whilst the role of qualitative data was to provide a better insight into the experiences and values of the patients that would encourage their participation in the larger, definitive study. The findings of this trial highlighted the specific issues of the patient population, the logistic challenges and provided some possible solutions to facilitate patient participation.

Biological effects are known to occur with ultrasound energy at kilohertz frequencies. This has led to research into its use as a non-invasive tool for tissue healing and repair. The aim of this research is to investigate the in vitro application of kilohertz ultrasound and to measure the biological responses using models of dental pulp cells which play an important role in dental repair. Ultrasound emitted from a longwave therapy instrument (DuoSon, SRA Developments Ltd) was characterised and measured identifying the range and intensity of the field. These measurements, coupled with biological data, identified the difficulties when conducting research with kilohertz ultrasound in vitro and indicated that the use of multi-well culture plates is not appropriate when investigating the effects of kilohertz ultrasound in cell culture. An improved method for in vitro kilohertz ultrasound application was devised enabling the investigation of non-thermal ultrasound effects on primary human dental cells. Cell proliferation, viability and gene expression, including the dental-related and biomechanically-responsive gene, dentine matrix protein-1, responded in a dose-dependent manner with respect to the duration of ultrasound application. These findings highlight the complexity of the biophysical interaction of kilohertz ultrasound with cells and demonstrate the need for further clarification of specific ultrasound settings for optimal therapeutic application. This study has demonstrated a positive effect of kilohertz ultrasound on human dental pulp cells and has identified methods to improve in vitro cell culture models to capture robust data to develop a novel therapy for dental repair.

The aim of this study was to gain a better understanding of the uptake of new mobile technologies and how they are utilized by staff and students in dental education. A questionnaire was distributed to students at the University of Birmingham, Dental School. Follow up one-to-one interviews were conducted. Tutors were interviewed to understand their attitude and understanding towards the use of electronic/mobile technologies. It is apparent that smartphones are more convenient for students to learn and as a resource to advice patients on their clinic. They are using them on the go in preference to any other device and use the support of mobile tools such as phone apps. Emails are used by students for more formal messages and Instant Messaging and social networking sites are used for shorter messages. Students thought that changes were necessary in the way that they communicate and research their studies. There is an all-embracing use, by both tutors and students of mobile learning tools. Learners wish to embed tools such as Instant Messaging in their learning areas but not without the approval of their respected tutors. Institutions should be aware of such changes and look to adapt their learning practices to mobile technologies.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the aetiologic agent of Kaposi’s sarcoma (KS), a malignancy characterised by spindle-shaped tumour cells with an endothelial phenotype that line primitive vascular structures. This thesis examines the concept that KSHV infection of primary endothelial cells alters their migration, supporting development of the extensive aberrant angiogenesis seen in KS.Primary human umbilical vein endothelial cells were infected with KSHV and their migration examined at time points between one and ten days post-inoculation. Infected cells transmigrated preferentially across porous filters compared to untreated or non-infected cells, and wounds in inoculated monolayers closed more rapidly compared to untreated cultures. Several cellular properties which might regulate cell migration rates were altered by KSHV inoculation. The virus modulated the laminin profile of the sub-endothelial matrix by reducing laminin-P1 deposition but increasing that of the laminin-a4 chain. No effect on deposition of either fibronectin or collagen IV was found. An increase in cell-surface expression of the lamininbinding integrin-a6 subunit was also detected with infection. Furthermore, KSHV infection partitioned actin stress fibres to the cell cortex and reduced the size and number of focal adhesions per cell. These results support a pro-migratory, pro-angiogenic effect of KSHV on endothelial cells that might be targeted to treat KS.

Current treatment of epithelial wounds utilise biomimetic materials, cells or a combination of both. This project aimed to examine the feasibility of incorporating mesenchymal stem cells (MSCs), isolated from adipose tissue and dental pulp, and induced pluripotent stem cells (iPSC)-derived cells into 3D organotypic cultures, as reports suggest MSCs facilitate wound healing and can generate constituent cells. The effect collagen hydrogels containing MSCs on H400 epithelial cells seeded on its surface was assessed. Fixed H&E-stained sections of organotypic cultures were used to determine epithelial maturation and thickness using image analysis. iPSCs generated using the STEMCCA lentivirus were assessed by gene expression analysis and immunofluorescent staining for pluripotent capabilities and keratinocyte differentiation. MSCs incorporated into collagen hydrogels exerted no effect on epithelial thickness. iPSCs generated from mouse adipose-derived stem cells (mADSC- iPSCs) expressed pluripotency markers and were capable of differentiating down embryonic lineages. Keratinocytes generated from mADSC-iPSCs expressed cytokeratins, but were unable to be cultured in 3D organotypic cultures. This thesis highlighted the importance of characterising stem cells when investigating their therapeutic potential. Future work will involve characterising MSCs and evaluating their effects on epithelial cell growth. Furthermore, the effects of iPSC-derived keratinocytes must be determined to exploit them for regenerative therapies.

Glasgow Dental School (GDS) offers a varied learning environment for well-motivated, high-achieving students. These students, along with institutional, professional and public stakeholders, demand high quality, efficient, effective and modern teaching practices. A new undergraduate curriculum was introduced at GDS; a more authentic learning experience was to be delivered with a move away from traditional teaching based solely within the dental hospital. Outreach teaching facilities were introduced and a cohort of NHS clinical tutors joined academic staff. Both new and old staff were required to develop their teaching skills. Some tutors expressed distress at the lack of availability of training to enhance teaching skills, and implementation of a Peer Observation of Teaching Scheme (POT) was considered as a way to address this issue. POT focuses on providing opportunities for staff to improve their teaching skills. It can be conducted successfully with inexperienced teaching staff and limited resources. It can help identify and eliminate poor teaching practice while enabling participants to develop their skills, self-identity and group identity as teachers. POT, in this study, is a reciprocal process whereby one peer observes another teaching and provides supportive and constructive feedback. Its underlying rationale is to encourage professional development in teaching and learning through critical reflection, by both the observer and the observed. In this thesis, I outline the implementation of the POT scheme across clinical sites at GDS. The study involved multiple stakeholders and therefore required approval, accommodation and support across six geographically diverse Scottish health board areas. The process and outcomes from the evaluation of the POT scheme are presented. The current body of published research offers little in relation to POT for the development of teaching chair-side clinical dentistry, a distinct area where students carry out multiple invasive procedures on patients during each teaching session. Appraisal of the scheme and its impact was conducted using evaluation methodology underpinned by constructivist epistemology. Ethical approval was sought and granted. Results describe motivations to teach and evaluation of the POT process in relation to its authenticity, acceptability and practicality. Analysis of who is truly considered a ‘peer’ as well as aspects of trust, honesty and respect are presented along with the perceived issues for colleagues sharing critical feedback. Impact of the POT scheme is explored in terms of teaching, reflection, increased self-awareness, and lessons learned about personal teaching practice. There is a strong focus on the role of POT for quality enhancement. Key issues highlighted by the findings include; the notable differences between participants from a range of academic backgrounds; study limitations; and feasible alternatives for the development of teaching staff. The POT scheme was successfully implemented and analysed. It was an authentic method for encouraging reflection and development of teaching practice. Recommendations for further progress are outlined. These include whether POT should be mandatory; how to facilitate wider group discussion; systems for implementation of shared good practice; and increasing access to teaching qualifications. Further research is required to directly measure the impact of POT on student learning and look at how the scheme has impacted on development of the wider community of practice.

Simulation in the shape of the “phantom head” is an essential part of every dental training programme. It is used to provide the student with practice before he/she is allowed to carry out restorative dental procedures on patients. In theory, this practice promotes patient safety. However, the learning process lacks clarity, and we do not understand fully how well learned skills transfer to clinical activity. This study asks whether in fact the pre-clinical course is a reliable guarantor of patient safety. It does so by examining four facets of the simulation process: purpose, learning, fidelity and transition, using a mixture of research methods, including comparison of pre-clinical and clinical assessment grades, focus groups with students, one-to-one interviews with their teachers and a questionnaire. The results of these investigations indicate a complex inter-relationship between purpose, learning, fidelity and transition. They also suggest that success in simulated restorative dentistry is a poor predictor of clinical ability, a limitation that needs careful consideration in the light of patient safety. The study recommends changes to increase the complexity and authenticity of the pre-clinical course, and suggests that the student transition needs detailed management, perhaps through a blend of pre-clinical and clinical activity.

Sri Lanka is a developing South Asian country which provides free education and healthcare for all its citizens. This thesis presents a policy-oriented study, partly empirical and partly modelling, whose aim was to understand dental care provision and workforce planning, at a time where Sri Lanka‟s dental health policies appear to have failed to achieve their intended results, leading to a mismatch between supply and demand, i.e. “underemployment and unemployment” of trained dental surgeons, despite an increasing need for dental care within the population. The first section of this thesis describes a novel method of collecting primary data on Sri Lanka‟s dental health professionals, in a challenging setting where there was no existing database. The thesis also presents a methodology to convert need for dental care to demand for care, adapting an existing model developed by the World Health Organization and the Federation Dentaire Internationale to suit the Sri Lankan setting. Finally, this section of the thesis describes a survey to identify the “timings” taken for various dental treatment modalities in Sri Lanka. The second section of the thesis presents a System Dynamics model, which uses the data obtained from these empirical surveys, to address dental workforce planning issues in Sri Lanka. The model is then used to simulate various different scenarios, generating realistic, practical and insightful lessons for policy making. Based on the results of this model, in 2011 the Government of Sri Lanka took steps to deal with the “employment mismatch” issue by restricting the annual intake of dental students and by creating 400 new Government-funded posts over the following two years.

The treatment of challenging large osseous defects presents a formidable problem for orthopaedic and maxillofacial surgeons. Autogenous bone grafting is the present method of choice to replace the lost tissue, but supplies of autologous bone are limited and harvesting of the graft is associated with donor site morbidity. Artificial biomaterials hold much promise, but do not, by themselves, supply the osteoprogenitor cells needed for bone formation. Moreover, there are often issues with resorption of the scaffold used in the biomaterial, as well as limited vascularity. This study investigates the novel application of a composite bone mineral (Cerament TM Spine Support) as an injectable bone cement loaded with cytokines and seeded with induced mesenchymal stromal cells, for maxillofacial reconstruction in rabbits. This study aims to test the feasibility of converting a pedicled muscle flap into bone to reconstruct a critical-size defect in the mandible as the above three components would theoretically have the combined effect of osteoconduction, osteoinduction and osteogenesis. The study included a comprehensive assessment of bone regeneration using plain radiography, Cone Beam computerized Tomography (CBCT), Micro-Computerized Tomography (micro-CT) and histology. Results at 3 months following surgery showed areas of bone formation and remnants of residual cement throughout the muscle and connective tissue in the surgical defect. Data analysis showed that complete bone integration or incorporation for the reconstruction of the surgical defect was not achieved. However, the regenerated bone displayed a high degree of remodeling with an intricate network of woven bone trabeculae within the cement. The bone was thicker in the bucco-lingual direction and exhibited more red and fatty marrow spaces compared to the contralateral (non-operated) side. The study confirmed that bone formation within a muscle flap in the maxillofacial region is possible. However, a wide range of variation in the patterns of bone formation was seen among the samples. The findings demonstrated the remarkable potential for the use of autologous muscle flaps as bioreactors for injectable scaffoldings, BMP, rMSCs to facilitate the reconstruction of maxillofacial bony defects.

The extracellular glucosyltransferases of Streptococcus sanguis polymerise the glucosyl moiety of sucrose to form high molecular weight complex glucans. The adhesive and agglutinative properties of these glucans are important in the formation of dental plaque and, hence, in cariogenesis. The glucosyltransferases of S. sanguis 804 (NCTC) were extensively purified (182-fold) by hollow fibre ultrafiltration (Bio-Fiber 80) followed by ammonium sulphate precipitation (0–70% of saturation). The enzymes were further purified by hydroxylapatite chromatography and appeared by this technique to consist of at least three enzymes with differing specific activities. It is not known whether these enzymes are, in fact, composed of different polypeptides or are modified forms of one protein. The activity of the glucosyltransferases can be measured as the rate of release of fructose from sucrose or as the rate of synthesis of ethanol-sodium acetate-precipitable polysaccharide (glucan). Using the former method, Kapp for sucrose for (NH4) 2SO4-purified glucosyltransferases was about 6 mmol/l and, using the latter method, Kapp was about 20 mmol/l. Glucosyltransferase activity (as rate of glucan synthesis) was stimulated 2 to 4-fold by low concentrations (0.125-0.50 μmol/l) of T2000 Dextran (Pharmacia; mol. wt. 2 × 106). Glucan synthesis was inhibited slightly by nigerose and was inhibited strongly by metrizamide (85% inhibition at 170 μmol/l metrizamide). The rate of release of fructose was not affected by either xylitol or hydrogen peroxide. The rate of synthesis of precipitable glucan was strongly inhibited by high concentrations of substrate (sucrose); the rate of release of fructose was relatively unaffected. The proposed mechanism for this effect is that sucrose acts as an alternative glucosyl acceptor (as well as donor) and thus inhibits glucosyl transfers to growing glucan chains. The oral concentrations of sucrose during and after consumptions of various sweet foods and beverages were studied and were often sufficient to inhibit glucan synthesis. In such cases, the sucrose concentrations for maximum rate of glucan synthesis only occurred as sucrose was cleared from the mouth, after the food or drink was finished. Glucan synthesis by S. sanguis is important in plaque formation. Thus, these results provide an additional explanation for the clinical finding that the incidence of caries is related to the frequency of dietary intake of sucrose and not merely the total amount of sucrose consumed.