Title:
Development of Noninvasive Methods for Monitoring Tissue Engineered Constructs using Nuclear Magnetic Resonance

dc.contributor.advisor Sambanis, Athanassios
dc.contributor.author Stabler, Cheryl Lynn en_US
dc.contributor.committeeMember Chaikof, Elliot L.
dc.contributor.committeeMember Ioannis Constantinidis
dc.contributor.committeeMember Robert C Long, Jr
dc.contributor.committeeMember Stephen Hanson
dc.contributor.department Biomedical Engineering en_US
dc.date.accessioned 2005-03-03T22:09:15Z
dc.date.available 2005-03-03T22:09:15Z
dc.date.issued 2004-04-12 en_US
dc.description.abstract Implanted tissue engineered substitutes constitute dynamic systems, with remodeling mediated by both the implanted cells and the host. Thus, there exists a significant need for methods to monitor the function and morphology of tissue engineered constructs. Noninvasive monitoring using 1H Nuclear Magnetic Resonance (NMR) spectroscopy and imaging can prove to be the solution to this problem. Spectroscopy allows for assessment of cellular function through the monitoring of inherent metabolic markers, such as total-choline, while high resolution imaging enables the evaluation of construct morphology and interfacial remodeling. We applied these 1H NMR methods to monitor betaTC3 mouse insulinoma cells within hydrogel-based materials as a model pancreatic tissue substitute. In vitro research established a strong correlation between total-choline, measured by 1H NMR spectroscopy, and viable betaTC3 cell number, measured by MTT. Extending these methods to in vivo monitoring, however, was met with additional challenges. First, the implanted cells needed to be contained within a planar construct above a threshold density to allow for adequate quantification of the total-choline peak. Secondly, cell-free buffer zones between the implanted cells and the host tissue needed to be incorporated to prevent host tissue signal contamination. Finally, quantitative techniques needed to be developed to accurately account for contaminating signal from diffusing molecules. To overcome these challenges, a disk-shaped agarose construct, initially containing a minimum of 4 million betaTC3 cells and coated with an outer layer of pure agarose, was fabricated. Mathematical simulations aided the implant design by characterizing diffusive transport of nutrients and metabolites into and out of the construct. In vivo 1H NMR studies of these constructs implanted in mice established a strong correlation between total-choline, measured noninvasively using 1H NMR spectroscopy, and viable cell number, measured invasively using MTT. This study establishes total-choline as a reliable marker for noninvasively quantifying dynamic changes in viable betaTC3 cell number in vivo. 1H NMR imaging was used to monitor the implants structural integrity over time, while also assessing the hosts fibrotic response. We expect these studies to establish quantitative criteria for the capabilities and limitations of NMR methodologies for monitoring encapsulated insulinomas, as well as other tissue implants. en_US
dc.description.degree Ph.D. en_US
dc.format.extent 3671424 bytes
dc.format.mimetype application/pdf
dc.identifier.uri http://hdl.handle.net/1853/5239
dc.language.iso en_US
dc.publisher Georgia Institute of Technology en_US
dc.subject Agarose en_US
dc.subject NMR
dc.subject Bioartificial pancreas
dc.subject Alginate
dc.subject.lcsh Spectrum analysis en_US
dc.subject.lcsh Pancreas Imaging en_US
dc.subject.lcsh Nuclear magnetic resonance en_US
dc.subject.lcsh Magnetic resonance imaging en_US
dc.subject.lcsh Diagnostic imaging en_US
dc.subject.lcsh Alginates en_US
dc.title Development of Noninvasive Methods for Monitoring Tissue Engineered Constructs using Nuclear Magnetic Resonance en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Sambanis, Athanassios
local.contributor.corporatename Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 90a12241-15c3-4cbf-bc27-724c028b8fc1
relation.isOrgUnitOfPublication da59be3c-3d0a-41da-91b9-ebe2ecc83b66
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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