dc.contributor.advisor	Guldberg, Robert E.
dc.contributor.author	Dupont, Kenneth Michael	en_US
dc.contributor.committeeMember	Garcia, Anes J.
dc.contributor.committeeMember	Peister, Alexana
dc.contributor.committeeMember	Temenoff, Johnna
dc.contributor.committeeMember	Zamir, Evan
dc.contributor.department	Mechanical Engineering	en_US
dc.date.accessioned	2011-07-06T16:49:06Z
dc.date.available	2011-07-06T16:49:06Z
dc.date.issued	2010-01-19	en_US
dc.description.abstract	Large bone defects pose a significant clinical challenge currently lacking an adequate therapeutic solution. Bone tissue engineering (BTE) therapies aim to provide that solution by combining structural scaffolds, bioactive factors, and/or osteogenic cells. Cellular therapies are likely vital to repair severe defects in patients lacking sufficient endogenous cells. Stem cells are attractive cell choices due to their osteogenic differentiation and extensive proliferation abilities, but their therapeutic potential is still uncertain, as studies comparing stem cell sources and delivery methods have produced inconsistent results. In this thesis, we developed a challenging in vivo large bone defect model for quantitative comparison of human stem cell-based therapies and then evaluated the abilities of adult or fetal stem cell-seeded constructs to enhance defect repair, with or without added osteogenic cues. First, we showed that cellular construct treatment enhanced defect healing over acellular construct treatment, although there were no differences between adult or fetal cell sources. We next labeled stem cells with a fluorescent tracking agent, the quantum dot, to determine biodistribution of implanted cells during the repair process. While quantum dots effectively labeled cells in vitro, they were ineffective in vivo tracking agents due to false positive signals and detrimental effects on stem cell-mediated repair. Finally, we developed a novel gene therapy technique using virus-coated scaffolds to deliver the osteogenic factor bone morphogenetic protein 2 (BMP2) to defect sites, either by in vitro (BMP2 transduction of seeded stem cells pre-implantation) or in vivo (BMP2 transduction of defect-site host cells) means. While defect-site BMP2 delivery through gene therapy methods improved repair, in vivo therapy enhanced healing more than stem cell-based in vitro therapy. This finding does not rule out the potential of stem cell-based in vitro gene therapy treatment for functional bone repair, as increases in viral dose may improve stem cell-mediated healing, but it does present evidence of a novel acellular BTE therapy with potential off-the-shelf clinical application in large bone defect repair, as scaffolds could be virally coated with the gene for BMP2 expression and frozen until implantation.	en_US
dc.description.degree	Ph.D.	en_US
dc.identifier.uri	http://hdl.handle.net/1853/39647
dc.publisher	Georgia Institute of Technology	en_US
dc.subject	Imaging	en_US
dc.subject	In vivo	en_US
dc.subject	Gene therapy	en_US
dc.subject	Stem cells	en_US
dc.subject	Bone tissue engineering	en_US
dc.subject.lcsh	Bone regeneration
dc.subject.lcsh	Bone substitutes
dc.subject.lcsh	Quantum dots
dc.title	Human stem cell delivery and programming for functional regeneration of large segmental bone defects	en_US
dc.type	Text
dc.type.genre	Dissertation
dspace.entity.type	Publication
local.contributor.advisor	Guldberg, Robert E.
local.contributor.corporatename	George W. Woodruff School of Mechanical Engineering
local.contributor.corporatename	College of Engineering
relation.isAdvisorOfPublication	5de086eb-63e8-46e3-b1cc-3569bb13e59c
relation.isOrgUnitOfPublication	c01ff908-c25f-439b-bf10-a074ed886bb7
relation.isOrgUnitOfPublication	7c022d60-21d5-497c-b552-95e489a06569

Title: Human stem cell delivery and programming for functional regeneration of large segmental bone defects

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Human stem cell delivery and programming for functional regeneration of large segmental bone defects