Revealing the 3D nanoscale structure and composition of healthy and diseased bone and teeth

这项海外旅行资助提案的一个中心目标是建立一个由骨骼和牙齿形成方面的专业知识的领先研究人员组成的网络，这些研究人员都相信，对矿物和有机相的纳米级组织的全面了解是开发医疗新方法的核心。所提出的方法是利用高分辨率电子成像和光谱学的进步来深入了解纳米尺度上的3D结构和组成。这种方法对于充分理解骨和牙齿结构形成背后的机制和潜在的失效机制具有重要意义。在最近的一篇论文中（Reznikov et al., Science 2018），我们能够识别出从纳米到宏观尺度的12个骨骼组织水平，在不同的长度尺度上出现了自相似的组织模式。这些发现表明了在纳米尺度上理解矿化组织结构的重要性。基于这项工作，我的目标是探索利用先进的电子显微镜和光谱学对矿化组织（如骨细胞和牙齿）的纳米级成像的应用。在这两种情况下，获得健康和患病组织中矿物质/有机组合的完整图像都是非常令人兴奋的。骨骼和牙齿中矿物质和有机相之间的复杂相互作用似乎强烈影响所产生的生物矿物质的特性，并且由于矿化影响疾病（例如成骨不完全性或淀粉不完全性、骨质疏松症、关节炎）而在纳米尺度上造成破坏的显著影响。因此，这项工作将为未来与领先的生命科学家和临床医生的合作提供一个平台，并将通过所选方法获得的高分辨率信息与诊断观察联系起来。蒙特利尔的麦吉尔大学和哈特福德的康涅狄格大学都为培训和研究提供了理想的条件，因为它们在健康相关材料研究方面具有良好的国际声誉，并提供了一套出色的实验技术来实现本提案的目标。

A central goal of this Overseas Travel Grant proposal is the establishment of a network of leading researchers with expertise in bone and tooth formation who share the believe that a comprehensive understanding of the nanoscale organization of both mineral and organic phase is at the heart of the development of new approaches for medical treatments. The proposed methodology is making use of the advancement of high-resolution electron imaging and spectroscopy to gain insights into the 3D structure and composition on the nanoscale. This approach is of great importance for a full understanding of the mechanisms behind structure formation and potential failure mechanisms in bones and teeth.In a recent publication (Reznikov et al., Science 2018) we were able to identify 12 levels of organisation in bone from the nano- to the macroscopic scale with a self-similar organisation pattern emerging across the different length-scales. These findings indicate the importance to understand the structure of mineralised tissue on the nanoscale.Based on this work I aim to explore the application of nanoscale imaging using advanced electron microscopy and spectroscopy to mineralised tissue such as bone cells and teeth.In both cases it is highly exciting to gain a full image of the mineral/organic assembly in healthy and disease affected tissues.The complex interplay between the mineral and the organic phases in bones and teeth appears to strongly affect the properties of the resulting biomineral with significant effects of disruptions on the nanoscale due to mineralisation affecting diseases (e.g. osteogenesis imperfecta or amelogenesis imperfecta, osteoporosis, arthritis). Hence, this work will provide a platform for future collaboration with leading life scientists and clinicians and will enable to link the high-resolution information gained by the chosen approaches with diagnostic observations.Both hosts at McGill University in Montreal and University of Connecticut in Hartford provide ideal conditions for both training and research since they have an excellent international reputation on health related materials research and provide access to an outstanding set of experimental techniques to achieve the goals of this proposal.