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dc.contributor.authorStabler, Cheryl Lynnen_US
dc.date.accessioned2005-03-03T22:09:15Z
dc.date.available2005-03-03T22:09:15Z
dc.date.issued2004-04-12en_US
dc.identifier.urihttp://hdl.handle.net/1853/5239
dc.description.abstractImplanted 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.format.extent3671424 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.subjectAgaroseen_US
dc.subjectNMR
dc.subjectBioartificial pancreas
dc.subjectAlginate
dc.subject.lcshSpectrum analysisen_US
dc.subject.lcshPancreas Imagingen_US
dc.subject.lcshNuclear magnetic resonanceen_US
dc.subject.lcshMagnetic resonance imagingen_US
dc.subject.lcshDiagnostic imagingen_US
dc.subject.lcshAlginatesen_US
dc.titleDevelopment of Noninvasive Methods for Monitoring Tissue Engineered Constructs using Nuclear Magnetic Resonanceen_US
dc.typeDissertationen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentBiomedical Engineeringen_US
dc.description.advisorCommittee Chair: Athanassios Sambanis; Committee Member: Elliot Chaikof; Committee Member: Ioannis Constantinidis; Committee Member: Robert C Long, Jr; Committee Member: Stephen Hansonen_US


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