Atom-by-atom, multispectral, and real-time characterization for osseous applications

每年有200多万加拿大人因骨质疏松症、关节置换和种植牙等骨骼或与骨骼有关的疾病接受治疗，这是一个巨大的财政和社会负担。我提出了一个雄心勃勃的计划，旨在开发工具，用于表征和理解骨的结构和生物成分之间的关系，如胶原纤维和细胞网络跨越纳米到微米尺度。这将为深入了解与骨形成、结构、性质以及骨与植入物的相互作用机制相关的重要问题提供帮助。 当前骨组织成像模式的一个主要挑战是其范围有限，无论是在探测体积、达到的分辨率还是时间灵敏度方面。因此，使用材料科学的方法，该提案的目的是开发一套相关的成像方法的表征技术的最前沿，能够同时表征和跨所有长度尺度，骨组织的结构，化学，时间和生物成分。通过利用加拿大电子显微镜中心独一无二的基础设施和我的研究小组内的既定专业知识，该提案将开发方法，以推进骨组织表征的三个领域，（i）原子探针断层扫描的原子检测，（ii）离子束显微镜的多光谱3D成像，以及（iii）原位显微镜的实时分析。 该提案代表了先进显微镜最前沿的几项创新，并将克服现有的挑战，在多个长度和时间尺度上对骨材料进行成像。这项研究将为我们提供一个全面的平台，以解决与骨形成，结构和材料整合相关的科学问题。这项及时的研究将通过阐明结构和生物学联系，阐明形成机制，并阐明与合成生物材料的相互作用，最终促进我们对骨组织的理解。高素质人才（HQP）在这一领域的培训是至关重要的，在加拿大工业先进成像，生物材料设计和表征，先进制造业的既定和新兴的职业生涯。 这项创新的研究将最终为我们提供一个更深入的认识的基本过程中的解决方案上级比通常的研究。开发一个针对骨质应用的表征技术平台对加拿大不断增长和老龄化的社会至关重要。该提案将在多个空间，光谱和时间维度上实现前所未有的分辨率，以提高我们对加拿大人骨和生物材料植入物的基本理解。

Over 2 million Canadians are treated annually for osseous or bone-related conditions, such as osteoporosis, joint replacement, and dental implant placement, representing a large financial and societal burden. I propose an ambitious program aimed at developing tools for characterizing and understanding the relationship between the structural and biological components of bone, such as collagen fibrils and cellular networks spanning the nano to microscale. This will provide insights into important questions related to the mechanisms of bone formation, structure, properties, and the interaction of bone with implants. A major challenge with current imaging modalities for bone tissue is their limited scope, either in terms of volume probed, resolution achieved, or time sensitivity. Therefore, using a materials science approach, this proposal aims to develop a suite of correlative imaging approaches at the forefront of characterization techniques, capable of characterizing simultaneously and across all length scales, the structural, chemical, temporal, and biological components of bone tissue. By utilizing the one-of-a-kind infrastructure at the Canadian Centre for Electron Microscopy and the established expertise within my research group, this proposal will develop methodologies to advance three areas of bone tissue characterization in, (i) atom-by-atom detection with atom probe tomography, (ii) multispectral 3D imaging with ion beam microscopes, and (iii) real-time analysis with in situ microscopy. This proposal represents several novelties at the forefront of advanced microscopy and will overcome existing challenges for imaging osseous materials across multiple lengths and time scales. This research will provide us with a comprehensive platform to tackle scientific questions related to bone formation, structure, and integration with materials. This timely research will ultimately advance our understanding of bone tissue by elucidating the structural and biological connections, shed light on formation mechanisms, and elucidate the interactions with synthetic biomaterials. The training of highly qualified personnel (HQP) in this area is crucial for established and emerging careers in Canadian industry in advanced imaging, biomaterials design and characterization, and advanced manufacturing. This innovative research will ultimately provide us with a more in-depth knowledge of the fundamental processes of mineralization at a resolution superior to usual studies. The development of a platform of characterization techniques tailored to osseous applications is critical for Canada's growing and aging society. This proposal will enable unprecedented resolution in multiple spatial, spectroscopic and temporal dimensions to improve our fundamental understanding of bone and biomaterials implants for Canadians.