Title:
Regulatory Mechanisms in the Chondrogenesis of Mesenchymal Progenitors: The Roles of Cyclic Tensile Loading and Cell-Matrix Interactions

Simple item page
dc.contributor.advisor Levenston, Marc E.
dc.contributor.author Connelly, John Thomas en_US
dc.contributor.committeeMember Anes J. Garcia
dc.contributor.committeeMember Barbara D. Boyan
dc.contributor.committeeMember Joseph Le Doux
dc.contributor.committeeMember Ravi Bellamkonda
dc.contributor.department Mechanical Engineering en_US
dc.date.accessioned 2007-08-16T17:59:30Z
dc.date.available 2007-08-16T17:59:30Z
dc.date.issued 2007-06-14 en_US
dc.description.abstract Cartilage tissue engineering represents an exciting potential therapy for providing permanent and functional regeneration of healthy cartilage tissues, but these treatment options have yet to be successfully implemented in a clinical setting. One of the primary obstacles for cartilage engineering is obtaining a sufficient supply of cells capable of regenerating a functional cartilage matrix. Mesenchymal progenitors can easily be isolated from multiple tissues, expanded in vitro, and possess a chondrogenic potential, but it remains unclear what types or combinations of signals are required for lineage-specific differentiation and tissue maturation. The overall goal of this dissertation was to investigate how the coordination of biochemical stimuli with cues from mechanical forces and the extracellular matrix regulate the chondrogenesis of bone marrow stromal cells (BMSCs). These studies explored the potential for cyclic tensile loading and chondrogenic factors, TGF-1 and dexamethsone, to promote fibrochondrocyte-specific differentiation of BMSCs. The application of cyclic tensile displacements to cell-seeded fibrin constructs promoted fibrochondrocyte patterns of gene expression and the development of a fibrocartilage-like matrix. These responses were influenced by the specific loading conditions examined and the differentiation state of the BMSCs. Additionally, the roles of integrin adhesion and cytoskeletal organization in BMSC differentiation were examined within engineered hydrogels presenting controlled densities of biomimetic ligands. Adhesion to the arginine-glycine-aspartic acid (RGD) motif inhibited chondrogenesis in a density-dependent manner and was influenced by interactions with the f-actin cytoskeleton. Together, this research provided fundamental insights into the regulatory mechanisms involved in the chondrogenesis of mesenchymal progenitor cells. en_US
dc.description.degree Ph.D. en_US
dc.identifier.uri http://hdl.handle.net/1853/16316
dc.publisher Georgia Institute of Technology en_US
dc.subject Chondrogenesis en_US
dc.subject Stem cells en_US
dc.subject Tension en_US
dc.subject Extracellular matrix en_US
dc.subject Tissue engineering en_US
dc.title Regulatory Mechanisms in the Chondrogenesis of Mesenchymal Progenitors: The Roles of Cyclic Tensile Loading and Cell-Matrix Interactions en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.corporatename George W. Woodruff School of Mechanical Engineering
local.contributor.corporatename College of Engineering
relation.isOrgUnitOfPublication c01ff908-c25f-439b-bf10-a074ed886bb7
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
connelly_john_t_200708_phd.pdf
Size:
9.83 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Theses and Dissertations