Development of Osteoinductive Tissue Engineering Scaffolds with a Bioreactor

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dc.contributor.advisorMikos, Antonios G.en_US
dc.contributor.committeeMemberGrande-Allen, K. Janeen_US
dc.contributor.committeeMemberZygourakis, Kyriacosen_US
dc.contributor.committeeMemberDrezek, Rebekah A.en_US
dc.contributor.committeeMemberKasper, Kurten_US
dc.contributor.committeeMemberJansen, Johnen_US
dc.creatorThibault, Richarden_US
dc.date.accessioned2013-07-24T19:48:59Zen_US
dc.date.accessioned2013-07-24T19:49:06Zen_US
dc.date.available2013-07-24T19:48:59Zen_US
dc.date.available2013-07-24T19:49:06Zen_US
dc.date.created2012-12en_US
dc.date.issued2013-07-24en_US
dc.date.submittedDecember 2012en_US
dc.date.updated2013-07-24T19:49:07Zen_US
dc.description.abstractThe conventional treatments for craniofacial bone defects currently are unsatisfactory due to several drawbacks. Replacement of lost bone by autografts typically causes donor site morbidity while allografts, xenografts, and demineralized bone matrix all have a chance of disease transmission. Current synthetic implants placed within the defect site generally lack osseointegration and biodegradability. There are several methods of generating a hybrid extracellular matrix (ECM) and synthetic material construct. These include coating the synthetic material scaffold with collagen and calcium phosphate, incorporating acellular biological tissue within the scaffold material, and using cells to generate an ECM coating on the synthetic material scaffold. The research performed for this thesis developed and characterized mesenchymal stem cell (MSC)-generated extracellular matrix poly(ε-caprolactone) constructs (PCL/ECM) for the replacement of bone tissue. The osteogenic potential of the PCL/ECM constructs was explored by culturing i) MSCs and ii) whole marrow cells combined with MSCs onto the construct with or without the osteogenic differentiation supplement, dexamethasone. It was established that the osteogenic differentiation of MSCs seeded onto ECM-containing constructs was maintained even in the absence of dexamethasone and that the co-culture of MSCs and whole bone marrow cells without dexamethasone and ECM enhances the proliferation of a cell population (or populations) present in the whole bone marrow. The osteogenicity of the constructs encouraged the characterization of the protein and mineral composition of the ECM coating on the PCL/ECM constructs. Characterization revealed that at short culture durations the MSCs used to generate the ECM deposited cellular adhesion proteins that are a prerequisite protein network for further bone formation. At the later culture durations, it was determined that the ECM was composed of collagen 1, hydroxyapatite, matrix remodeling proteins, and regulatory proteins. The prior studies on the PCL/ECM constructs persuaded exploration of the effect of various devitalization and demineralization processes on the retention of the ECM components within and the osteogenicity of the PCL/ECM constructs. Analysis demonstrated that the freeze-thaw technique is a milder method of devitalization of cell-generated ECM constructs as compared to other methods, but it reduced the osteogenicity of the constructs. In addition, it was elucidated that void spaces in the surface of the constructs are important for allowing access of MSCs into the interior of the constructs.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationThibault, Richard. "Development of Osteoinductive Tissue Engineering Scaffolds with a Bioreactor." (2013) Diss., Rice University. <a href="https://hdl.handle.net/1911/71696">https://hdl.handle.net/1911/71696</a>.en_US
dc.identifier.slug123456789/ETD-2012-12-266en_US
dc.identifier.urihttps://hdl.handle.net/1911/71696en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectBoneen_US
dc.subjectTissue engineeringen_US
dc.subjectExtracellular matrixen_US
dc.subjectScaffolden_US
dc.subjectMesenchymal stem cellsen_US
dc.titleDevelopment of Osteoinductive Tissue Engineering Scaffolds with a Bioreactoren_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBioengineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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