The collagen network plays a critical role in determining functional properties of cartilage and other extracellular matrices. The collagen network exerts a retractive stress on the osmotically active proteoglycans trapped within it in much the same way a balloon's rubber membrane exerts a hydrostatic pressure of the gas contained within it. Until now, however, it has not been possible to measure important physical properties of the collagen network independently of other constituents within the extracellular matrix. Recently, we devised a new methodology to determine structural properties of the collagen network per se, such as its bulk modulus. This new approach entails (a) modeling the cartilage tissue matrix as a composite material consisting of two distinct phases: a collagen network and a proteoglycan (PG) solution trapped within it, (b) applying various known levels of equilibrium osmotic stress, and (c) using physical-chemical principles and independent experiments to determine useful """"""""pressure-volume"""""""" relations for both the PG and collagen phases independently. In pilot studies, we used this approach to determine pressure-volume curves for the collagen network and the PG phases in native and in trypsin treated normal human cartilage specimen, as well as in cartilage specimen from osteoarthritic (OA) joints. In both normal and trypsin-treated specimen, collagen network stiffness appeared unchanged,whereas in the OA specimen, collagen network stiffness decreased. Our findings highlight the role of the collagen network in limiting normal cartilage hydration, and in ensuring a high PG concentration in the matrix, both of which are essential for effective load bearing in cartilage, but are lost in OA. These data also suggest that the loss of collagen network stiffness, and not the loss or modification of PGs may be the incipient event leading to the subsequent disintegraton of cartilage observed in OA. Recently, Kimberlee Potter has initiated microscopic Magnetic Resonance Imaging (MRI) studies designed to estimate parameters of our mathematical model of cartilage swelling noninvasively by attempting to relate the chemical composition of cartilage tissue grown in a hollow-fiber bioreactor to various measurable MRI parameters. Ferenc Horkay is now developing an instrument that will enable us to study swelling properties of extremely thin cartilage sections, permitting us to obtain a profile its functional properties with depth from a joint's articular surface.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2000
Total Cost
Indirect Cost
Name
U.S. National Inst/Child Hlth/Human Dev
Department
Type
DUNS #
City
State
Country
United States
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Chandran, Preethi L; Horkay, Ferenc (2012) Aggrecan, an unusual polyelectrolyte: review of solution behavior and physiological implications. Acta Biomater 8:3-12
Geissler, E; Hecht, A-M; Horkay, F (2010) Scaling behaviour of hyaluronic acid in solution with mono- and divalent ions. Macromol Symp 291-292:362-370
Horkay, Ferenc; Basser, Peter J; Hecht, Anne-Marie et al. (2008) Gel-like behavior in aggrecan assemblies. J Chem Phys 128:135103
Bencherif, Sidi A; Srinivasan, Abiraman; Horkay, Ferenc et al. (2008) Influence of the degree of methacrylation on hyaluronic acid hydrogels properties. Biomaterials 29:1739-49
Michelman-Ribeiro, Ariel; Horkay, Ferenc; Nossal, Ralph et al. (2007) Probe diffusion in aqueous poly(vinyl alcohol) solutions studied by fluorescence correlation spectroscopy. Biomacromolecules 8:1595-600
Lin, David C; Dimitriadis, Emilios K; Horkay, Ferenc (2007) Robust strategies for automated AFM force curve analysis--I. Non-adhesive indentation of soft, inhomogeneous materials. J Biomech Eng 129:430-40
Horkay, Ferenc; Hecht, Anne Marie; Rochas, Cyrille et al. (2006) Anomalous small angle x-ray scattering determination of ion distribution around a polyelectrolyte biopolymer in salt solution. J Chem Phys 125:234904
Horkay, Ferenc; Horkayne-Szakaly, Iren; Basser, Peter J (2005) Measurement of the osmotic properties of thin polymer films and biological tissue samples. Biomacromolecules 6:988-93
Lin-Gibson, Sheng; Bencherif, Sidi; Cooper, James A et al. (2004) Synthesis and characterization of PEG dimethacrylates and their hydrogels. Biomacromolecules 5:1280-7
Stubbe, Barbara G; Horkay, Ferenc; Amsden, Brian et al. (2003) Tailoring the swelling pressure of degrading dextran hydroxyethyl methacrylate hydrogels. Biomacromolecules 4:691-5

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