Articular cartilage lines the opposing surfaces of articulating joints, providing a durable, low-friction bearing surface. Injuries to the articular cartilage frequently fail to heal, resulting in chronic pain and debility. Current treatment options for advanced osteoarthritis are limited, and generally do little to prevent further degradation of the joint. Using tissue engineering principles, it may be possible to develop bioartificial tissues which could be implanted in the joint, effectively repairing the damage and preventing further breakdown. These studies investigated the development of tissue engineered cartilage for joint repair. Specifically, they looked at the effects of mechanical compression on tissue engineered cartilage constructs in vitro, with the hope of gaining new insights into how the mechanical environment may be used to enhance and direct construct growth. Engineered cartilages were cultured under oscillatory compression, and the resulting changes in gene expression and matrix synthesis were measured. The effects of mechanical compression were found to vary with different scaffold systems. In some tissue engineered environments, oscillatory compression stimulated cartilage gene expression and matrix synthesis. In other environments, oscillatory compression inhibited matrix accumulation and stimulated catabolic activity.
These studies also investigated the use of an in vitro cartilage defect repair model to estimate how engineered tissues may respond to biological and biomechanical stimuli in the treated joint. Cartilage repair was modeled using a hybrid culture system, consisting of an annulus of explanted articular cartilage surrounding a central defect. This defect was filled with an engineered cartilage, and the resulting repair was assessed using various biochemical and mechanical tests. When these hybrid constructs were grown under oscillatory compression, an increase in matrix synthesis and expression of genes for matrix proteins was observed. Finite element analysis of the system suggested that fluid pressurization may play an important role in regulating matrix synthesis in the repair environment.
This work demonstrates the importance of the mechanical and biochemical environment in modulating and directing the growth of tissue engineered cartilage. Application of proper stimuli to the treated joint could enhance the repair process and increase the chances of fully restoring joint functionality.
Some of the work in this dissertation has been previously presented or submitted for publication, and reflects the contributions of my co-authors. Material from Chapter VI has been submitted to Biomaterials1 and was presented at the 46th Annual Meeting of the Orthopaedic Research Society2. Material from Chapter VII was presented at the 2001 BMES Annual Fall Meeting3. Material from Chapter VIII was presented at the Third Biennial Meeting of the Tissue Engineering Society4 and at the 2001 BMES Annual Fall Meeting5. Material from Chapter X has been submitted to Biorheology6 and was presented at the 2nd International Symposium on Mechanobiology of Cartilage and Chondrocyte7/
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