The Woodruff School

SUMMARY

Articular cartilage provides a low-friction surface during normal joint motion and distributes forces to the underlying bone. The extracellular matrix (ECM) composition of healthy cartilage has previously been shown to be an excellent predictor of its mechanical properties. Changes in ECM composition and loss of mechanical function are known to occur with degenerative conditions such as osteoarthritis. Identifying differences in the composition-function relationships of cartilage under different anabolic, catabolic, and homeostatic conditions may thus be a useful approach for identifying factors (e.g. ECM content, distribution, and structure) which are critical to mechanical function. In addition, diagnostic tools capable of monitoring changes in the cartilage ECM may increase our understanding of the effects of ECM changes on composition-functions relationships. The goals of this work were to investigate composition-function relationships in healthy, degraded, and engineered cartilage and to develop a uCT-based approach to analyze changes in matrix composition and morphology in articular cartilage. In healthy explants, compressive and shear properties were dependent on both sGAG and collagen content. In contrast, the compressive properties of IL-1 �stimulated cartilage were dependent on sGAG but not collagen content. To assess changes in sGAG content, EPIC-uCT, a 3D contrast-enhanced microcomputed tomography technique was developed. EPIC-uCT attenuation was found to be an excellent predictor of sGAG content in IL-1-stimulated cartilage explants and engineered cartilage. In addition, analytical approaches were developed to use EPIC-uCT for the in situ analysis of cartilage morphology. EPIC-uCT was also used to analyze spatial differences in sGAG accumulation in bilayer engineered cartilage for comparison with the local strain profile. This work underscores the significance of ECM composition and structure in regulating cartilage mechanical properties and validates the use of EPIC-uCT as a diagnostic for monitoring sGAG content and potentially for assessing mechanical function in models of degeneration and regeneration.

SUBJECT:	Ph.D. Dissertation Defense

BY:	Ashley Palmer

TIME:	Tuesday, February 27, 2007, 10:00 a.m.

PLACE:	Whitaker Ford Building, 1214

TITLE:	Investigations of the Composition-Function Relationships in Normal, Degraded, and Engineered Articular Cartilage Using EPIC-Microcomputed Tomography

COMMITTEE:	Dr. Marc Levenston, Chair (ME) Dr. Ravi Bellamkonda (BME) Dr. Robert Guldberg (ME) Dr. Robert Sah (BE, UCSD) Dr. Raymond Vito (ME)

SUMMARY Articular cartilage provides a low-friction surface during normal joint motion and distributes forces to the underlying bone. The extracellular matrix (ECM) composition of healthy cartilage has previously been shown to be an excellent predictor of its mechanical properties. Changes in ECM composition and loss of mechanical function are known to occur with degenerative conditions such as osteoarthritis. Identifying differences in the composition-function relationships of cartilage under different anabolic, catabolic, and homeostatic conditions may thus be a useful approach for identifying factors (e.g. ECM content, distribution, and structure) which are critical to mechanical function. In addition, diagnostic tools capable of monitoring changes in the cartilage ECM may increase our understanding of the effects of ECM changes on composition-functions relationships. The goals of this work were to investigate composition-function relationships in healthy, degraded, and engineered cartilage and to develop a uCT-based approach to analyze changes in matrix composition and morphology in articular cartilage. In healthy explants, compressive and shear properties were dependent on both sGAG and collagen content. In contrast, the compressive properties of IL-1 �stimulated cartilage were dependent on sGAG but not collagen content. To assess changes in sGAG content, EPIC-uCT, a 3D contrast-enhanced microcomputed tomography technique was developed. EPIC-uCT attenuation was found to be an excellent predictor of sGAG content in IL-1-stimulated cartilage explants and engineered cartilage. In addition, analytical approaches were developed to use EPIC-uCT for the in situ analysis of cartilage morphology. EPIC-uCT was also used to analyze spatial differences in sGAG accumulation in bilayer engineered cartilage for comparison with the local strain profile. This work underscores the significance of ECM composition and structure in regulating cartilage mechanical properties and validates the use of EPIC-uCT as a diagnostic for monitoring sGAG content and potentially for assessing mechanical function in models of degeneration and regeneration.