Behavior of passaged chondrocytes in collagen-glycosaminoglycan scaffolds : effects of cross-linking, mechanical loading, and genetic modification of the scaffold

Tissue engineering is a promising solution to the problematic healing of cartilage defects. The purpose of this thesis was to establish a foundation for the development of a collagen-glycosaminoglycan (CG) scaffold for articular cartilage tissue engineering by exploring the behavior of passaged chondrocytes in the CG scaffolds under the influence of a variety of environmental factors. Using in vitro studies, the first two parts of the thesis evaluated the effects of the physical environment on the behavior of adult, passaged chondrocytes in the CG scaffold. Scaffold cross-linking procedures increased cross-link density and scaffold stiffness and increased resistance to cell-mediated degradation and contraction as follows: dehydrothermal treatment (DHT) < ultraviolet irradiation (UV) < gluteraldehyde (GTA) < carbodiimide (EDAC). EDAC scaffolds also provided for the highest levels of cell proliferation and protein and GAG synthesis throughout a 4-week culture. Static mechanical compression (0-50% strain) applied to cell-seeded EDAC cross-linked scaffolds decreased rates of protein and GAG synthesis while dynamic compression (3% sine amplitude, 0.1 Hz) increased rates of biosynthesis over a 24-hour period. These results were similar to those of prior studies of loading of intact cartilage explants. Unlike the explant studies, however, dynamic compression failed to increase the accumulation of matrix molecules within the construct compared to unloaded ("free-swelling") controls because of a large increase in the release of newly synthesized macromolecules into the media.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Mechanical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2002

Author dc:creator

• Lee, Cynthia R. (Cynthia Renee), 1975-

Advisor dc:contributor.advisor

• Myron Spector.

• Mechanical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/89881

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/89881