? 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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE015322-02
Application #
6920709
Study Section
Special Emphasis Panel (ZRG1-SSS-M (01))
Program Officer
Lumelsky, Nadya L
Project Start
2004-08-01
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
2
Fiscal Year
2005
Total Cost
$363,375
Indirect Cost
Name
Case Western Reserve University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Whitney, G Adam; Kean, Thomas J; Fernandes, Russell J et al. (2018) Thyroxine Increases Collagen Type II Expression and Accumulation in Scaffold-Free Tissue-Engineered Articular Cartilage. Tissue Eng Part A 24:369-381
Dennis, James E; Bernardi, Kristina G; Kean, Thomas J et al. (2018) Tissue engineering of a composite trachea construct using autologous rabbit chondrocytes. J Tissue Eng Regen Med 12:e1383-e1391
Whitney, G Adam; Jayaraman, Karthik; Dennis, James E et al. (2017) Scaffold-free cartilage subjected to frictional shear stress demonstrates damage by cracking and surface peeling. J Tissue Eng Regen Med 11:412-424
Kean, Thomas J; Mera, Hisashi; Whitney, G Adam et al. (2016) Disparate response of articular- and auricular-derived chondrocytes to oxygen tension. Connect Tissue Res 57:319-33
Whitney, G A; Mansour, J M; Dennis, J E (2015) Coefficient of Friction Patterns Can Identify Damage in Native and Engineered Cartilage Subjected to Frictional-Shear Stress. Ann Biomed Eng 43:2056-68
Kean, Thomas J; Dennis, James E (2015) Synoviocyte Derived-Extracellular Matrix Enhances Human Articular Chondrocyte Proliferation and Maintains Re-Differentiation Capacity at Both Low and Atmospheric Oxygen Tensions. PLoS One 10:e0129961
Whitney, G Adam; Mera, Hisashi; Weidenbecher, Mark et al. (2012) Methods for producing scaffold-free engineered cartilage sheets from auricular and articular chondrocyte cell sources and attachment to porous tantalum. Biores Open Access 1:157-65
Henderson, James H; Ginley, Nell M; Caplan, Arnold I et al. (2010) Low oxygen tension during incubation periods of chondrocyte expansion is sufficient to enhance postexpansion chondrogenesis. Tissue Eng Part A 16:1585-93
Gilpin, David A; Weidenbecher, Mark S; Dennis, James E (2010) Scaffold-free tissue-engineered cartilage implants for laryngotracheal reconstruction. Laryngoscope 120:612-7
Weidenbecher, Mark; Tucker, Harvey M; Gilpin, David A et al. (2009) Tissue-engineered trachea for airway reconstruction. Laryngoscope 119:2118-23

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