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

通过多模态相关显微镜和多物理场建模应对人类龋齿

基本信息

批准号：
EP/P005381/1
负责人：
Alexander Korsunsky
金额：
$ 225.4万
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FP005381%2F1
关键词：
Tackling human dental caries multi

项目摘要

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.

人类矿化的牙齿组织是人体中最坚硬的组织，它代表了自然界在各个尺度上的分层工程的一个有趣的例子，从天然生长的羟基磷灰石晶体在牙釉质和牙本质形成期间的原子水平组装到它们并入有机基质纳米复合物中以及生长成宏观牙齿，其实现对牙齿的存在和良好的生长至关重要的复杂的长期作用，地球上每一个人的存在。它是大自然设计的光辉典范。然而，在人类龋齿的例子中，现代高糖饮食、牙菌斑形成细菌和由它们产生的酸性环境引起的脱矿物质的结合破坏了复杂的进化过程。在工业化国家，龋齿影响60-90%的学龄儿童和绝大多数成年人，仍然是最持久和最具挑战性的疾病之一，引起疼痛，痛苦和不安。虽然水氟化控制这种疾病的进展是有据可查的，但在大多数情况下，牙医的指示集中在改变生活方式和口腔卫生的建议上，实际上效率有限。根据英国健康和社会保健信息中心（HSCIC）的最新（2016年）报告，英国儿童的蛀牙率连续四年稳步上升。国家新闻头条（www.bbc.co.uk/news/health-35672775）报道的这些令人震惊的数字使这一研究课题成为焦点，这意味着拟议项目的成果可能会产生显着的科学和社会影响。在这项提案中，我们希望通过进行系统的、协调的、多尺度的显微镜调查，加上数字疾病建模，以更好地诊断、积极干预和治疗龋齿，来应对龋齿的挑战。通过将这种联合，交叉相关的分析方法应用于纳米级多模态显微镜和建模（牛津）和牙科研究和教学（伯明翰）的专家对相同样品的分析，我们将在FIB-SEM和先进的X射线方法观察到的超微结构，化学和成分变化之间建立紧密联系，以及通过传统牙科技术观察到的图案，颜色，信号和迹象。提议者与地球仪各地的大学和大型设施研究团体、牙科公司和执业牙医有着广泛的合作关系。OHI Ltd.和Specialists Dental Group作为合作伙伴的参与，以及Tescan和Diamond Light Source（DLS）的安全支持将增加并加速影响。这将为新的解释方法和治疗程序铺平一条切实有效的道路。我们将桥梁的见解，从纳米尺度的表征，以传统的牙科技术（X射线摄影和组织学）。我们将建立一个多尺度模型，作为一个预测工具，以指导制定最有前途的战略，克服龋齿。该项目的目标与EPSRC医疗保健技术大挑战的各个方面密切相关，回答了开发未来疗法，控制所需物理干预量，优化治疗以及改变社区卫生和护理的主题。与此同时，我们将为推进跨领域研究能力做出贡献，这对实现这些重大挑战至关重要。特别是，这项研究将开发采用多模态显微镜的新型成像技术，并利用所获得的见解，通过制定和验证复杂的疾病和治疗数值模型，在计算和数学科学中创造新的方法。这项工作也将有利于先进材料和颠覆性传感和分析技术领域。