dc.contributor.author | Micheletti, Chiara | |
dc.date.accessioned | 2023-05-16T14:05:33Z | |
dc.date.available | 2023-05-16T14:05:33Z | |
dc.date.issued | 2023-05-16 | |
dc.identifier.isbn | 978-91-8069-183-3 (print) | |
dc.identifier.isbn | 978-91-8069-184-0 (PDF) | |
dc.identifier.uri | https://hdl.handle.net/2077/75903 | |
dc.description.abstract | 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. | en |
dc.language.iso | eng | en |
dc.relation.haspart | I. Micheletti C, Jolic M, Grandfield K, Shah FA, Palmquist A. Bone structure and composition in a hyperglycemic, obese, and leptin receptor-deficient rat: Microscale characterization of femur and calvarium. Bone. 2023;172:116747. https://doi.org/10.1016/j.bone.2023.116747 | en |
dc.relation.haspart | II. Micheletti C, DiCecco L-A, Larsson Wexell C, Binkley DM, Palmquist A, Grandfield K, Shah FA. Multimodal and multiscale characterization of the bone-bacteria interface in a case of medication-related osteonecrosis of the jaw. JBMR Plus. 2022;6:e10693. https://doi.org/10.1002/jbm4.10693 | en |
dc.relation.haspart | III. Micheletti C, DiCecco L-A, Deering J, Chen W, Ervolino da Silva AC, Shah FA, Palmquist A, Okamoto R, Grandfield K. Micro-to-nanoscale characterization of the osseointegration and lacuno-canalicular network at the interface with an additively manufactured implant for local genistein delivery. Submitted for publication. | en |
dc.relation.haspart | IV. Gomes-Ferreira PHS, Micheletti C, Buzo Frigério P, de Souza Batista FR, Monteiro NG, Bim-júnior O, Lisboa-Filho PN, Grandfield K, Okamoto R. PTH 1-34-functionalized bioactive glass improves peri-implant bone repair in orchiectomized rats: Microscale and ultrastructural evaluation. Biomater Adv. 2022;134:112688. https://doi.org/10.1016/j.msec.2022.112688 | en |
dc.relation.haspart | V. Micheletti C, Gomes-Ferreira PHS, Casagrande T, Lisboa-Filho PN, Okamoto R, Grandfield K. From tissue retrieval to electron tomography: Nanoscale characterization of the interface between bone and bioactive glass. J R Soc Interface. 2021;18:20210181. https://doi.org/10.1098/rsif.2021.0181 | en |
dc.relation.haspart | VI. Micheletti C, Shah FA, Palmquist A, Grandfield K. Shedding light (… electrons) on human bone ultrastructure with correlative on-axis electron tomography and energy-dispersive X-ray spectroscopy tomography. Submitted for publication. Preprint available in bioRxiv: https://doi.org/10.1101/2023.04.20.537681 | en |
dc.subject | bone | en |
dc.subject | osseointegration | en |
dc.subject | characterization | en |
dc.subject | mineralization | en |
dc.subject | ultrastructure | en |
dc.subject | diabetes | en |
dc.subject | osteoporosis | en |
dc.subject | MRONJ | en |
dc.subject | surface functionalization | en |
dc.subject | local drug delivery | en |
dc.subject | titanium | en |
dc.subject | bioactive glass | en |
dc.subject | imaging | en |
dc.subject | spectroscopy | en |
dc.subject | microscale | en |
dc.subject | nanoscale | en |
dc.subject | micro-computed X-ray tomography | en |
dc.subject | micro-Raman spectroscopy | en |
dc.subject | scanning electron microscopy | en |
dc.subject | transmission electron microscopy | en |
dc.subject | PFIB-SEM tomography | en |
dc.subject | electron tomography | en |
dc.title | Multimodal and multiscale characterization of bone and bone interfaces in health and disease | en |
dc.type | text | eng |
dc.type.svep | Doctoral thesis | eng |
dc.gup.mail | chiara.micheletti@biomaterials.gu.se | en |
dc.type.degree | Doctor of Philosophy (Medicine) | en |
dc.gup.admin | Thesis in cotutelle with McMaster University,
Department of Materials Science and Engineering
Hamilton, ON, Canada | en |
dc.gup.origin | University of Gothenburg. Sahlgrenska Academy | en |
dc.gup.department | Institute of Clinical Sciences. Department of Biomaterials | en |
dc.gup.defenceplace | Måndagen den 12 juni 2023, kl. 13.00, Hörsal Arvid Carlsson, Academicum, Medicinaregatan 3, Göteborg | en |
dc.gup.defencedate | 2023-06-12 | |
dc.gup.dissdb-fakultet | SA | |