Interspecies characterization and tissue engineering of the temporomandibular joint disc
Kalpakei, Kerem Nathan
Athanasiou, Kyriacos A.
Doctor of Philosophy
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.