Title:
In Vitro and In Vivo Characterization of a Cell Source for Bone Tissue Engineering Applications: Primary Bone Marrow Stromal Cells Overexpressing the Osteoblast-Specific Transcriptional Activator Runx2/Cbfa1

dc.contributor.advisor García, Andrés J.
dc.contributor.author Byers, Benjamin Allen en_US
dc.contributor.committeeMember Barbara D. Boyan
dc.contributor.committeeMember Grace K. Pavlath
dc.contributor.committeeMember Joseph M. LeDoux
dc.contributor.committeeMember Julia E. Babensee
dc.contributor.committeeMember Guldberg, Robert E.
dc.contributor.department Mechanical Engineering en_US
dc.date.accessioned 2005-03-03T22:12:53Z
dc.date.available 2005-03-03T22:12:53Z
dc.date.issued 2004-02-12 en_US
dc.description.abstract Bone tissue engineering strategies are currently being developed as alternative mechanisms to address the clinical demand for bioactive and biomechanical graft material. To date, these efforts have been largely restricted by inadequate supply of committed osteoprogenitor cells and loss of osteoblastic phenotype expression following in vitro culture and expansion. The objective of this thesis research was to address the cell sourcing limitations of tissue-engineered bone grafts through constitutive and sustained overexpression of the osteoblast-specific transcriptional activator Runx2/Cbfa1 in osteogenic marrow-derived stromal cells using retroviral gene delivery. Runx2 overexpression enhanced expression of multiple osteoblastic genes proteins and, more importantly, significantly up-regulated matrix mineralization in both monolayer culture and following cell seeding in 3-D polymeric scaffolds. To evaluate in vivo performance, Runx2-expressing cells were seeded into 3-D constructs and implanted both subcutaneously and in a critical size craniotomy bone defect model. Notably, in vitro pre-culture of Runx2-transduced cell-seeded constructs prior to implantation significantly enhanced their capacity to form mineralized tissue in the subcutaneous space and induce new bone formation in the critical size defect model compared to control cells. The described series of analyses provided a novel combination of tissue and genetic engineering techniques toward the development of a Runx2-modified stromal cell/polymeric scaffold composite tissue-engineered bone graft substitute. en_US
dc.description.degree Ph.D. en_US
dc.format.extent 13712628 bytes
dc.format.mimetype application/pdf
dc.identifier.uri http://hdl.handle.net/1853/5260
dc.language.iso en_US
dc.publisher Georgia Institute of Technology en_US
dc.subject Mineralization en_US
dc.subject Stromal cells
dc.subject Genetic engineering
dc.subject Runx2/Cbfa1
dc.subject Tissue engineering
dc.subject Bone
dc.title In Vitro and In Vivo Characterization of a Cell Source for Bone Tissue Engineering Applications: Primary Bone Marrow Stromal Cells Overexpressing the Osteoblast-Specific Transcriptional Activator Runx2/Cbfa1 en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor García, Andrés J.
local.contributor.corporatename George W. Woodruff School of Mechanical Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication 6236e450-228b-4532-8b5e-812316ac90f3
relation.isOrgUnitOfPublication c01ff908-c25f-439b-bf10-a074ed886bb7
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
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