Research Project
6011661
Temporomandibular disorders are common among the general population, and the effects can be debilitating. Recent studies have emphasized the importance of osteoarthritis (degenerative joint disease) and inflammation in the pathogenesis of temporomandibular joint (TMJ) disorders. The growth of tissues in vitro for in vivo transplantation and repair (tissue engineering) has recently been demonstrated to have immense potential. Recent studies have demonstrated the ability to grow cartilage and meniscal constructs in vitro, for in vivo transplantation into knee joints. The objective of this proposal is to develop cartilage and disc tissue representative of TMJ tissues by tissue engineering. It is anticipated that the in vitro growth of the tissue engineered TMJ cartilage and disc constructs will be enhanced with the application of mechanical load and growth factors. Our governing hypothesis is that tissue engineered constructs similar to TMJ tissues can be generated using scaffolds with TMJ cells, and cultured under defined mechanical loads with selected growth factors. Specific Aim 1 is to (a) determine the capacity of cells from the articular cartilage and the disc of the TMJ to proliferate and maintain a phenotype that will allow construct formation in vitro; and (b determine the scaffold(s) that will support construct growth and generate a tissue similar to that of normal TMJ cartilage and disc. Specific Aim 2 is to determine the effect of (a) static and cyclic compressive loads, (b) fluid induced shear stress, and (c) growth factors (IGF1, TGFb and FGF) on the gene expression and synthesis of aggrecan, biglycan, decorin, caollgen I and II, in the bovine TMJ articular cartilage, and the posterior band and intermediate zone of the disc. Based on these results, we will develop a bioreactor system that will support tissue growth with imposition of the mechanical loads and stresses as identified in (a), (b) and (c). Specific Aim 3 is to determine the effect of specifically selected mechanically loading regimes, and potentially growth factors (as determined in Specific Aim 2), on the ability of cell-seeded scaffolds (as selected in Specific Aim 1) to form cartilage and disc tissue in vitro. The objective will be to use these variables to modulate tissue growth toward the properties and composition of normal TMJ tissues. The completion of these studies will provide the method for tissue engineering TMJ tissues appropriate for transplantation.
