? It is well accepted that cells respond both to soluble factors and to biomechanical forces by altering their gene expression. Chondrocytes from different anatomic locations all express a set of common matrix molecules, but those matrix molecules are either expressed at different levels or are assembled differently in cartilage at different anatomic locations. It is postulated that biomechanical forces in combination with local soluble factors are responsible for the differential assembly of the extracellular matrix. It is further hypothesized that by moving chondrocytes from one anatomic location to another, the chondrocytes will adopt the matrix structure of the implantation site. The objective of the proposed studies is to test this hypothesis using chondrocytes isolated from auricular, nasal, articular, and tracheal cartilage that have been expanded in culture and combined with a matrix that is conducive to cartilage production. These constructs of different anatomic origin will be switched into different anatomic sites, along with control constructs implanted back to their site of origin. Over time, the samples will be harvested and will undergo biomechanical, biochemical and immunohistochemical analyses to determine if the implanted chondrocytes have modulated their extracellular matrix to match the implant site. Prior to conducting the implant experiments, baseline data on the biochemical, biomechanical and immunohistochemical characteristics of native cartilage will be complied. Finally, chondrocytes will be tested in a pre-clinical model of laryngeal tracheal reconstruction in rabbits. This study addresses both the fundamental question of how complex matrix assembly is regulated and tests the practical use of easily-obtained auricular chondrocytes in a preclinical model for laryngeal-tracheal reconstruction that will test whether transplanted engineered cartilage has sufficient biomechanical strength and long-term stability to be developed for use in humans. ? ?
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