Interspecies Characterization and Tissue Engineering of the Temporomandibular Joint Disc

Disorders of the temporomandibular joint (TMJ) are widespread, afflicting millions of people. The majority of these cases involve displacement or injury to the TMJ disc. Current treatments do not fully address severe cases of TMJ dysfunction; therefore, efforts to engineer functional tissues for repair or replacement are warranted. While previous studies have laid the groundwork for these efforts, significant challenges remain, including (1) identification of appropriate animal models, (2) development of methodologies for in vitro TMJ tissue engineering, and (3) refinement of tissue culture procedures for clinically relevant cells sources. This thesis contributes to overcoming these challenges by (1) exploring topographical and interspecies variation in functional properties of the TMJ disc, (2) developing an in vitro tissue engineering strategy capable of recapitulating native tissue characteristics, and (3) enhancing protocols for chondrogenesis of dermis-derived cells.

The first aim of this thesis characterized the biomechanical and biochemical properties of human TMJ disc in relation to several animal models. Significant regional and interspecies variations were indentified, though certain characteristics were observed across all species. While the human disc displayed properties distinct from the other species, the pig was the most similar and was therefore identified as the most appropriate animal model. The second aim applied these findings as design criteria in the development of an in vitro tissue engineering strategy. Scaffoldless constructs derived from co-cultures of chondrocytes and fibrochondrocytes were enhanced through optimization of growth factor and serum supplementation, such that they recapitulated many characteristics of native TMJ cartilage. Finally, the third aim refined the differentiation process for chondroinduction of dermis-derived cells. Using an optimized, low-cost surface coating, chondrogenesis was significantly enhanced through incorporation of hypoxia during culture. These experiments address several aspects of fibrocartilage tissue engineering and represent a significant step towards in vivo application of these technologies.

Year	Entry
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Year

Entry

2001

Gooch KJ, Blunk T, Courter DL, Sieminski AL, Bursac PM, Vunjak-Novakovic G, Freed LE. IGF-I and mechanical environment interact to modulate engineered cartilage development. Biochem Biophys Res Commun. September 7, 2001;286(5):909-915.

1995

Buschmann MD, Gluzband YA, Grodzinsky AJ, Hunziker EB. Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J Cell Sci. April 1995;108(4):1497-1508.

1998

Freed LE, Hollander AP, Martin I, Barry JR, Langer R, Vunjak-Novakovic G. Chondrogenesis in a cell-polymer-bioreactor system. Exp Cell Res. April 10, 1998;240(1):58-65.

1992

Parkkinen JJ, Lammi MJ, Helminen HJ, Tammi M. Local stimulation of proteoglycan synthesis in articular cartilage explants by dynamic compression in vitro. J Orthop Res. 1992;10(5):610-620.

1984

Palmoski MJ, Brandt KD. Effects of static and cyclic compressive loading on articular cartilage plugs in vitro. Arthritis Rheum. June 1984;27(6):675-681.