Cartilage Shaping for Biological Resurfacing/Replacement of the TMJ

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DESCRIPTION (provided by applicant): Temporomandibular joint disorders (TMJD), including osteoarthritis and internal derangement, have a high prevalence in the adult population and often cause pain and limited jaw function. Severe deterioration of the articular cartilage of the mandibular condyle can occur in advanced cases of TMJD and may necessitate surgical removal via condylectomy. Reconstruction of the mandibular condyle has been attempted using autogenous, allogeneic, and alloplastic grafts, but these implant materials are often associated with complications including donor site morbidity, risk of disease transmission, and immunogenic reaction. Tissue engineering of cartilage and bone may address the significant and unmet clinical need for treating TMJD through the ability to produce grafts with appropriate biological and mechanical properties. One approach to a tissue engineering based treatment for TMJD might be through the creation of an appropriately shaped chondral graft which could be used alone to resurface the condyle or integrated to an osseous substrate to reconstruct the entire condyle. The ability to shape cartilaginous tissues into anatomical forms could be an enabling technology to this treatment approach. Thus, the long-term goal of this project is to establish scientific principles and engineering methods for the creation of contoured articular cartilage grafts for the effective surgical treatment of TMJD. Recent studies have shown that shape changes can be induced in immature articular cartilage explants in vitro through the use of mechanical stimuli, particularly bending deformations. Our overall hypothesis is that the shape plasticity of articular cartilage may be differentially modulated by imbalances in proteoglycan (PG) and collagen (COL) remodeling (via BAPN or p-D-xyloside) and may be used advantageously to create grafts of the size and shape of human mandibular condyle cartilage. To test this hypothesis, we have two aims. Aim 1: Determine whether in vitro growth which favors PG or COL remodeling (via BAPN or P-D-xyloside, respectively) alters the shape plasticity of immature and mature articular cartilage. Aim 2: Determine whether chondral grafts of the size and shape of human mandibular condyle cartilage can be produced through the mechanical reshaping of articular cartilage explants. The successful outcome of this interdisciplinary study will be the identification of culture conditions and techniques which are conducive to the formation of anatomically shaped chondral tissues. These findings will have broad clinical implications for the use of regenerative medicine in the treatment of disorders of the TMJ and articulating joints, in general.