Mechanical stimulation of an in vitro articular cartilage defect repair model.

摘要

Articular cartilage lines the opposing surfaces of articulating joints, providing a durable, low-friction bearing surface. Due to its low cellularity and lack of vasculature, injuries to 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.; This dissertation included numerous studies investigating 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.