Recent studies have emphasized the importance of osteoarthritis (OA) in the pathogenesis of temporomandibular joint (TMJ) disorders. The cause of TMJ disorders has traditionally been attributed to displacement of the biconcave articular disc interposed between the articular surfaces rather than to changes in the cartilage lining the surfaces of the joint. As a result, a significant effort has been made to develop methods for replacing the articular disc using both tissue grafts and alloplastic materials, all of which have met with limited success. Given recent evidence for the causative roles of OA in disc displacement, restoration of the TMJ articular cartilage may be a more effective approach to restoring joint function. Several research efforts have focused on generating tissue engineered constructs for cartilage replacement due to the limited reparative ability of the natural tissue. Our proposal is premised on the notion that functional articular cartilage may be grown in vitro by cultivation of chondrocytes under conditions which mimic the native physiologic environment of cartilage. Current attempts to engineer cartilage are limited by a scarcity of chondrocytes. Recent work by the candidate has demonstrated that human dermal fibroblasts, which are readily available and generally considered to be restricted to a fibroblastic lineage, may be converted to chondrocytic cells under specialized culture conditions. These in vitro conditions simulate oxidative stresses and cell signaling cues that regulate cartilage development. The mechanical environment of articular cartilage is also known to modulate the cartilage-specific phenotype. Specifically, we and others have shown that dynamic deformational loading analogous to that seen in vivo stimulates matrix biosynthesis and enhances the mechanical properties of cartilaginous tissues grown in vitro. Based on these observations, the governing hypothesis of this proposal is that functional TMJ articular cartilage may be engineered from a human dermal fibroblast donor cell population by culture on tailored three-dimensional scaffolds exposed to biochemical signals and a dynamic loading regimen that approximates physiologic conditions. A custom bioreactor will be used to apply loads to cell-seeded composites and the most current techniques will be employed to determine the mechanical properties of native TMJ cartilage and engineered constructs. This work will not only have practical applications for maxillofacial surgery, but will also contribute to our knowledge of craniofacial and oral biology.
