Thesis in cotutelle with the University of Gothenburg,
Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy
Gothenburg, Sweden / Seeing is believing. Our understanding of phenomena often involves their direct observation. However, bone architecture is challenging to visualize given its multi-level hierarchical organization. In this thesis, bone and bone interfaces are characterized via multimodal and multiscale platforms, combining different techniques across several length scales. Imaging techniques across the micro-nano continuum are complemented by spectroscopy methods to explore, respectively, the structure and composition of bone and bone interfaces, using both light and electron probes. By applying a characterization methodology more typical of materials science, this thesis aims to unveil structural and compositional abnormalities of bone induced by disease [Papers I-II], and bone response to functionalized biomaterials in compromised conditions [Papers III-IV]. Additionally, it expands three-dimensional (3D) characterization opportunities at the nanoscale in both native and peri-implant bone [Papers V-VI].
This characterization approach uncovered changes in bone quality (structure and/or composition) in the compromised conditions under investigation in this thesis, i.e., leptin receptor (LepR) deficiency and medication-related osteonecrosis of the jaw (MRONJ) [Papers I-II]. In a preclinical model of LepR deficiency for type 2 diabetes/obesity, multimodal characterization of bone at the microscale showed structural abnormalities indicative of delayed skeletal development, despite unaffected bone matrix composition [Paper I]. A combination of multiscale imaging and spectroscopy techniques spanning the micro-to-nanoscale enabled a detailed study of the interface between necrotic bone and bacteria in a case of MRONJ, shedding light on possible mechanisms of bone degradation. When applied to bone-biomaterial interfaces, the application of a multimodal and multiscale characterization workflow informed perspectives on bone response to novel biomaterial solutions aimed to promote osseointegration in osteoporotic conditions via local drug delivery of phytoestrogens [Paper III] or anabolic agents [Paper IV]. This highlighted the importance of studying peri-implant bone at the mesoscale [Paper III] and of confirming biomaterial behaviour in vivo in the presence of surface functionalization [Paper IV]. Lastly, this thesis emphasized the importance of 3D imaging at the nanoscale with electron tomography to resolve bone ultrastructure at biomaterial interfaces [Paper V] and in native conditions [Paper VI]. Specifically, in Paper VI, artifact-free on-axis electron tomography resolved some long-debated aspects regarding the organization of mineralized collagen fibrils, the fundamental building block units of bone. / Thesis / Doctor of Philosophy (PhD) / Bone is a hierarchical material, meaning that smaller components are progressively organized into larger structures. This multi-level architecture is hard to visualize because different techniques are required to obtain information at different length scales. However, as the proverb says, “seeing is believing”, and our understanding of things is often better accomplished by looking at images. This thesis applies a characterization approach more typical of materials science to study the structure, composition, and repair of bone across multiple length scales. This characterization approach is multimodal because it uses different techniques, and multiscale because it targets different length scales in bone. In particular, this thesis focuses on bone in compromised conditions, namely osteoporosis, diabetes, and medication-related osteonecrosis, to understand the impact of disease-induced changes in bone properties. It also examines how bone organizes itself at a fundamental level, which is a critical aspect to understand since bone is built from the bottom-up.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/30494 |
| Date | January 2023 |
| Creators | Micheletti, Chiara |
| Contributors | Grandfield, Kathryn, Materials Science and Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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