| As the bearing material of diarthrodial joints, articular cartilage has remarkable functional properties that have been difficult to reproduce in tissue-engineered constructs. Our effort to engineer articular cartilage utilizes a “functional tissue engineering (FTE)” approach. The principle hypothesis of this approach is that by recreating in vitro some aspects of the in vivo environment, one can enhance the growth of a viable tissue construct. A major hypothesis of our work is that cartilage bioreactors must provide dynamic loading at controlled deformation and hydrostatic pressure magnitudes and frequencies to produce constructs with functional properties. In this thesis, the long-term application of dynamic deformational loading to chondrocyte-seeded agarose hydrogels is shown to dramatically increase the mechanical properties of these tissue constructs. Moreover, these mechanically induced increases in tissue properties are optimized by growth factor supplementation, increases in cell seeding density, increases in media volume and serum supplementation, and variations in the duty cycle of deformational loading. In addition to deformational loading, hydrostatic pressure, applied dynamically, may in some cases also enhance both matrix deposition and the material properties of these constructs. Together, these findings support the efficacy of a functional approach to the engineering of articular cartilage, wherein native physical signals are used direct the growth of a functional replacement tissue. Another long-term objective of our efforts is to engineer anatomically shaped articular layers that may be implanted in lieu of a prosthetic joint. To achieve this goal, we have used computer-aided design and manufacturing methodologies to produce chondrocyte-seeded agarose constructs in the shape of human articular surfaces (patella, trapeziometacarpal joint). To address the long-term concern of anchoring constructs unto the native bony substrate of diseased joints, we have produced and cultured agarose gel-devitalized trabecular bone composites, seeded with chondrocytes. Finally, we have developed analytical techniques to help identify the mechanisms, such as solute transport, that may enhance tissue elaboration with dynamic loading. This dissertation explores the above considerations for the functional tissue engineering of cartilage, and points to new avenues of research that will enhance our understanding of articular cartilage and our ability to engineer this unique tissue. |
