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、关节置换和牙种植体植入等骨质疏松症或骨相关疾病接受治疗，这带来了巨大的经济和社会负担。我提出了一个雄心勃勃的计划，旨在开发工具来表征和理解骨骼的结构和生物成分之间的关系，例如胶原蛋白纤维和跨越纳米到微米的细胞网络。这将为骨形成的机制、结构、特性以及骨与植入物的相互作用等重要问题提供深入的见解。 目前骨组织成像方式的一个主要挑战是它们的范围有限，无论是在探测体积、达到的分辨率还是在时间敏感性方面。因此，利用材料科学的方法，这项建议旨在开发一套相关的成像方法，处于表征技术的前沿，能够同时并跨所有长度尺度表征骨组织的结构、化学、颞骨和生物成分。 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成熟的专业知识，这项建议将开发方法学，以推进骨组织表征的三个领域，(I)使用原子探针断层摄影术进行逐个原子的检测，(Ii)使用离子束显微镜进行多光谱3D成像，以及(Iii)使用原位显微镜进行实时分析。 这项提议代表了先进显微技术前沿的几项创新，并将克服现有的挑战，即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来解决与骨形成、结构和与材料整合相关的科学问题。这一及时的研究最终将通过阐明骨组织的结构和生物联系，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。该领域高素质人才(HQP)的培训对于加拿大工业在先进成像、生物材料设计和表征以及先进制造领域的成熟和新兴职业至关重要。 这项创新的研究最终将以高于通常研究的分辨率为我们提供更深入的成矿基本过程知识。为骨骼应用量身定做的表征技术平台的开发对加拿大不断增长和老龄化的社会至关重要。这一提议将使我们能够在多个空间、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对骨和生物材料植入的基本理解。

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.