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

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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.