The high prevalence of osteoarthritis (OA) and the poor intrinsic healing capacity of articular cartilage has led to the development of cell-based strategies for cartilage repair. The initial granting period explored the novel application of physiologic deformational loading, a primary component of the chondrocyte physical enviornment in vivo, to precondition bovine chondrocyte-seeded 3D agarose hydrogel constructs in culture. Our goal has been to develop constructs with functional properties similar to the juvenile tissue from which the cells were derived. The two (2) most important insights that we have gained from our model agarose system are: (1) the application of physiologic deformational loading can promote development of constructs with better material properties than free-swelling controls only if sufficient nutrients are available; and (2) deformational loading may provide its beneficial effects on tissue construct growth via a mechanotransduction mechanism and/or solute transport mechanism. Building on our experience, we propose the following hypotheses: (1) Increasing concentration of amino acids in the culture media will promote development of constructs having higher material properties and protein content than constructs cultured basal amino acid levels. (2a) Unconfined compression will give rise to development of higher tensile modulus than compressive modulus in the radial direction (tension-compression nonlinearity), as well as higher tensile modulus in the radial direction compared to the axial direction (ansiotropy). The underlying mechanism reflects development of radial tensile strains during applied axial compressive loading. (2b) The unconfined compression loading configuration with a free impermeable platen and constraind lower impermeable platen will generate a lower Poisson's ratio (v) at the upper platen than at the lower platen. The underlying mechanism reflects the development of greater radial strains at the free upper platen that decreases to the confined lower platen. (3) Direct perfusion of medium through constructs will provide better material properties throughout the constructs, than free-swelling conditions. Direct perfusion and applied dynamic deformational loading will lead to synergistic effects on tissue growth. (4) Deformational loading will promote less construct surface roughness and better frictional properties than free-swelling constructs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR046568-05A2
Application #
6920422
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Panagis, James S
Project Start
2000-01-24
Project End
2008-12-31
Budget Start
2005-04-01
Budget End
2005-12-31
Support Year
5
Fiscal Year
2005
Total Cost
$307,434
Indirect Cost
Name
Columbia University (N.Y.)
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027
Nims, Robert J; Cigan, Alexander D; Durney, Krista M et al. (2017) * Constrained Cage Culture Improves Engineered Cartilage Functional Properties by Enhancing Collagen Network Stability. Tissue Eng Part A 23:847-858
Nover, Adam B; Hou, Gary Y; Han, Yang et al. (2016) High intensity focused ultrasound as a tool for tissue engineering: Application to cartilage. Med Eng Phys 38:192-8
Nover, Adam B; Stefani, Robert M; Lee, Stephanie L et al. (2016) Long-term storage and preservation of tissue engineered articular cartilage. J Orthop Res 34:141-8
Nover, Adam B; Lee, Stephanie L; Georgescu, Maria S et al. (2015) Porous titanium bases for osteochondral tissue engineering. Acta Biomater 27:286-293
Tan, A R; Alegre-Aguarón, E; O'Connell, G D et al. (2015) Passage-dependent relationship between mesenchymal stem cell mobilization and chondrogenic potential. Osteoarthritis Cartilage 23:319-27
Nims, Robert J; Cigan, Alexander D; Albro, Michael B et al. (2015) Matrix Production in Large Engineered Cartilage Constructs Is Enhanced by Nutrient Channels and Excess Media Supply. Tissue Eng Part C Methods 21:747-57
Cigan, Alexander D; Nims, Robert J; Albro, Michael B et al. (2014) Nutrient channels and stirring enhanced the composition and stiffness of large cartilage constructs. J Biomech 47:3847-54
Alegre-Aguarón, Elena; Sampat, Sonal R; Xiong, Jennifer C et al. (2014) Growth factor priming differentially modulates components of the extracellular matrix proteome in chondrocytes and synovium-derived stem cells. PLoS One 9:e88053
Ponnurangam, Sathish; O'Connell, Grace D; Chernyshova, Irina V et al. (2014) Beneficial effects of cerium oxide nanoparticles in development of chondrocyte-seeded hydrogel constructs and cellular response to interleukin insults. Tissue Eng Part A 20:2908-19
Nims, Robert J; Cigan, Alexander D; Albro, Michael B et al. (2014) Synthesis rates and binding kinetics of matrix products in engineered cartilage constructs using chondrocyte-seeded agarose gels. J Biomech 47:2165-72

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