Tackling human dental caries by multi-modal correlative microscopy and multi-physics modelling

Human mineralised dental tissues are the hardest tissues in the human body that represent an intriguing example of nature's hierarchical engineering across the scales, from the atomic level assembly of naturally grown hydroxyapatite crystals during amelo- and dentino-genesis to their incorporation into organic matrix nano-composite and the growth into macroscopic teeth that fulfil a complex long-term role crucial to the existence and well-being of every human being on the planet. It is a shining example of nature's design fit for purpose. However, in the instance of human dental caries, the combination of modern sugar-rich diet, plaque-forming bacteria and demineralisation caused by the acidic environment they produce defeats the intricate evolutionary process. In industrialized countries, dental caries affects 60-90% of schoolchildren and the vast majority of adults, remaining one of the most persistent and challenging diseases causing pain, suffering and upset. Although progress in controlling this disease by water fluoridation is well documented, in most cases dentist's instructions focus on recommendations for changes in the lifestyle and oral hygiene, in practice turning out to have limited efficiency. According to the latest (2016) report of the UK's Health and Social Care Information Centre (HSCIC), tooth decay in English children has been steadily rising for four years in a row. These alarming figures reported in national news headlines (www.bbc.co.uk/news/health-35672775) bring this research topic into sharp focus, meaning that the outcomes of the proposed project are likely to make notable scientific and societal impact. In this proposal we wish to tackle the caries challenge by undertaking a systematic, coordinated, multi-scale microscopic investigation, coupled with numerical disease modelling to move towards better diagnosis, and proactive intervention and treatment of caries. By applying this joined-up, cross-correlated analytical approach to the same samples by the specialists in nano-scale multi-modal microscopy and modeling (Oxford) and dental research and teaching (Birmingham), we will establish a tight connection between ultrastructural, chemical and compositional changes seen by FIB-SEM and advanced X-ray methods, and the patterns, colours, signals and signs observable by conventional dentistry techniques. The proposers have extensive partnership links with university and large facility research groups, dental companies and practicing dentists across the globe. Involvement of OHI Ltd. and Specialists Dental Group as partners, and the secured support from Tescan and Diamond Light Source (DLS) will increase and accelerate impact. This will pave a practical and efficient way to new interpretative approaches and treatment routines. We will bridge the insights from nano-scale characterization to conventional dentistry techniques (X-ray radiography and histology). We will build a multi-scale model that will serve as a predictive tool to guide the formulation of the most promising strategies for overcoming caries. The project objectives are closely aligned with all aspects of EPSRC Healthcare Technologies Grand Challenges, answering the topics of developing future therapies, controlling the amount of physical intervention required, optimizing treatment, and transforming community health and care. In parallel, we shall contribute to the advancement of Cross-Cutting Research Capabilities that are essential for delivering these Grand Challenges. In particular, this research will develop novel imaging technologies employing multi-modal microscopy, and use the insights obtained to create novel approaches in computational and mathematical sciences through the formulation and validation of sophisticated numerical models of disease and treatment. The work will also benefit the areas of advanced materials and disruptive technologies for sensing and analysis.