Item – Theses Canada

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OCLC number
1334504289
Link(s) to full text
LAC copy
Author
Szulc, Daniel Andrzej.
Title
Manganese-based Positive-contrast MRI for Non-invasive Monitoring of Biomaterials and Cells in Tissue Engineering.
Degree
Ph.D. -- University of Toronto, 2020.
Publisher
[Toronto, Ontario] : University of Toronto, 2020
Description
1 online resource
Abstract
Cells and scaffolds are the pillars of tissue engineering and regenerative medicine. They have the potential to regenerate any tissue or organ; however, a major unmet challenge limiting their clinical translation is the absence of non-invasive technologies for spatial and temporal tracking of implant fate in deep tissue and with high spatial resolution. Contrast-enhanced magnetic resonance imaging (CE-MRI) is highly suited for this task; however, current methods suffer from contrast agent toxicity or fail to provide longitudinal monitoring with high sensitivity and specificity. To address this need, this thesis aims to further develop positive-contrast MRI with manganese (Mn), an essential micronutrient, for in vivo imaging and tracking of cells and scaffolds. To image scaffolds and track their fate, biomaterials were labelled with manganese porphyrin (MnP) contrast agents, which exhibit anomalously high T1 relaxivity and form stable Mn-chelates. Atypical conjugation approaches were explored to achieve facile, biocompatible and efficient labelling of a variety of decellularized extracellular matrix and collagen-based scaffolds including injectable hydrogels, tissue grafts and whole organ constructs. This thesis demonstrates the first report to track these materials in vivo with CE-MRI and the potential for quantitative tracking of degradation over time. For non-invasive cellular MRI, both direct and indirect labelling techniques with Mn-based agents were designed to guide cell injection in real-time and probe cell fate longitudinally. Firstly, the utility of a commercially scalable MnP agent for safe and highly efficient labelling of human embryonic stem cells was demonstrated ex vivo. MR imaging of the labelled cells permitted detection of early cell fate and injection success in vivo. Secondly, to track cells longitudinally with high sensitivity and specificity, a reporter gene platform, bright-ferritin, was designed to produce endogenous T1-cellular contrast by the formation of manganese-ferritin nanoparticles intracellularly. The bright-ferritin system exhibited superior relaxivity and contrast generation in vitro and in vivo over conventional T2 iron-ferritin systems and T1 manganese-transporter systems. This bright-ferritin platform has the potential for on-demand, longitudinal, and sensitive, quantitative cell-tracking in vivo. Overall, this body of work demonstrates the utility of Mn-based bright-MRI for the assessment of scaffold and cell implantations.
Other link(s)
tspace.library.utoronto.ca
hdl.handle.net
Subject
Cell Tracking
Magnetic Resonance Imaging
Manganese
Porphyrin
Scaffold Monitoring
Tissue Engineering