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

这项海外旅行补助金提案的一个中心目标是建立一个由具有骨骼和牙齿形成专业知识的领先研究人员组成的网络，他们共同认为，对矿物和有机相的纳米级组织的全面理解是开发新的医疗方法的核心。所提出的方法利用高分辨率电子成像和光谱学的进步来深入了解纳米级的3D结构和组成。这种方法对于充分理解骨骼和牙齿中结构形成和潜在失效机制背后的机制非常重要。Science 2018），我们能够识别出骨骼中从纳米到宏观尺度的12个组织水平，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）进行纳米尺度成像的应用。在这两种情况下，获得矿物的完整图像是非常令人兴奋的。在健康和疾病影响的组织中的有机组装。骨骼和牙齿中的矿物和有机相之间的复杂相互作用似乎强烈影响所得生物矿物的性质，由于影响疾病的矿化作用而导致的纳米级破坏（例如，骨生成障碍或釉质生成障碍、骨质疏松症、关节炎）。因此，我们认为，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，并将使高-蒙特利尔麦吉尔大学和哈特福德康涅狄格大学的两个主办方都为培训和研究提供了理想的条件，因为他们在健康相关材料研究方面享有良好的国际声誉，并提供获得一套优秀的实验技术，以实现本提案的目标。

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.