This study proposes to establish a fundamental and theoretically consistent understanding of the load-bearing roles of the two major macromolecules (i.e., collagen and proteoglycans) of articular cartilage. For decades this had been a major goal in cartilage biology, biomechanics, biochemistry and osteoarthritis research. Progress over recent years has necessitated the development of a theory (i.e., the triphasic theory) capable of describing the extant mechano-electrochemical behaviors of articular cartilage in a consistent manner. Using the three apparatuses the investigators have constructed (for swelling-buoyancy, confined-compression-swelling and electrokinetic tests), and the theoretical models they have developed, they will attempt to determine a set of material properties to precisely characterize the mechano-electrochemical behaviors of the tissue. A fourth device, using the reverse-osmosis principle, will be developed during this granting period to extend the measurement of osmotic pressures of PG solutions to physiologic concentrations. To complete the full scope of required data, tensile and shear tests will also be performed. Data from all these tests, and results from predictions from relevant triphasic models, are necessary to validate the applicants' approach toward further understanding of the structure-function relationships of the tissue. The applicant indicates that from his instruments and theoretical models, his group can measure the true in situ volume fraction of collagen, the true density of collagen, extrafibrillar and intrafibrillar water volumes, effective fixed charge density, swelling pressure, Donnan osmotic pressure, and calculate the frictional coefficients between water and the solid matrix, between water and collagen, and between water and proteoglycan. Their ability to determine these properties has motivated a set of hypotheses on how collagen, proteoglycan, water and ions function to provide the compressive, tensile, shear, permeability, streaming potential properties of the tissue. Further, since there are three major morphologic zones in articular cartilage, each with its distinct distributions of collagen, proteoglycan, water and ionic contents, the proposed studies are aimed at determining the functional roles of each of these layers as well. All biochemical assays (S-GAG, hydroxyproline, collagen X-link density and enzymatic treatments) will be performed on the tested specimens, and on site- and depth-specific adjacent specimens. Skeletally-mature bovine knee joint articular cartilage will be used for the entire study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR041913-04A1
Application #
2404090
Study Section
Special Emphasis Panel (ZRG4-ORTH (03))
Project Start
1993-07-20
Project End
2000-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Orthopedics
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Likhitpanichkul, Morakot; Guo, X Edward; Mow, Van C (2005) The effect of matrix tension-compression nonlinearity and fixed negative charges on chondrocyte responses in cartilage. Mol Cell Biomech 2:191-204
Wan, Leo Q; Miller, Chester; Guo, X Edward et al. (2004) Fixed electrical charges and mobile ions affect the measurable mechano-electrochemical properties of charged-hydrated biological tissues: the articular cartilage paradigm. Mech Chem Biosyst 1:81-99
Sun, D D; Guo, X E; Likhitpanichkul, M et al. (2004) The influence of the fixed negative charges on mechanical and electrical behaviors of articular cartilage under unconfined compression. J Biomech Eng 126:6-16
Lu, X Lux; Sun, Daniel D N; Guo, X Edward et al. (2004) Indentation determined mechanoelectrochemical properties and fixed charge density of articular cartilage. Ann Biomed Eng 32:370-9
Gu, W Y; Sun, D N; Lai, W M et al. (2004) Analysis of the dynamic permeation experiment with implication to cartilaginous tissue engineering. J Biomech Eng 126:485-91
Wang, Christopher C-B; Guo, X Edward; Sun, Dongning et al. (2002) The functional environment of chondrocytes within cartilage subjected to compressive loading: a theoretical and experimental approach. Biorheology 39:11-25
Mow, Van C; Guo, X Edward (2002) Mechano-electrochemical properties of articular cartilage: their inhomogeneities and anisotropies. Annu Rev Biomed Eng 4:175-209
Lai, W M; Sun, D D; Ateshian, G A et al. (2002) Electrical signals for chondrocytes in cartilage. Biorheology 39:39-45
Huang, C Y; Mow, V C; Ateshian, G A (2001) The role of flow-independent viscoelasticity in the biphasic tensile and compressive responses of articular cartilage. J Biomech Eng 123:410-7
Wang, C C; Hung, C T; Mow, V C (2001) An analysis of the effects of depth-dependent aggregate modulus on articular cartilage stress-relaxation behavior in compression. J Biomech 34:75-84

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