Our long-term objective is to understand the etiology of cartilage degeneration during the osteoarthritic process, and more immediately, to develop a better understanding of those properties of cartilage which depend on the existence of proteoglycan charge groups in the extracellular matrix. Three general hypotheses have been proposed regarding the function of these charge groups: 1) the effective fixed charge density (i.e., total charge/extrafibrillar water)is the primary regulator of the kinetics of fluid and ion transport through cartilage; 2) the effective tissue hydration (i.e., extrafibrillar water content) is regulated by a balance of elastic stress and the total swelling pressure (i.e., sum of osmotic pressure and charge-to-charge repulsion stress); and 3) the swelling pressure is not primarily responsible for the resistance of cartilage to compression at equilibrium, but rather load support is provided by the bulk mechanical properties of the extracellular matrix. Our triphasic mechano-electrochemical model for cartilage was developed to specifically address the questions relating to the function of the fixed charge groups. This theory fills a very significant gap in the literature by providing a unified basis for the disparate physicochemical, mechanical and electrical data on cartilage. We have also shown that the triphasic theory extends, and is entirely consistent with, the specialized Donnan osmotic pressure theory, the Onsager, the Katchalsky and Kedem transport theories, and our biphasic theory, all of which have been commonly used to describe specific facets of cartilage behavior. From the triphasic model for cartilage, we now have explicit relations for the hydraulic permeability, electric conductivity and compressive modulus as a function of its effective fixed charge density, and other fundamental physicochemical variables (e.g., osmotic and activity coefficients). Our immediate objective is to test the hypotheses on the function of fixed charges in cartilage using a consistent set of experiments based on the predictions of this new thermodynamically permissible theory. A new electro-osmosis experiment is proposed, and an experimental prototype of this device has been constructed, to demonstrate our ability to directly measure fixed charge density, electrical resistance and hydraulic permeability on a single cartilage specimen. Collagen, collagen cross-link and proteoglycan contents will be measured, and correlated with all mechanical, physicochemical and electrical data. Skeletally-mature, bovine knee cartilage from the patellar groove will be used. The proposed set of cartilage data will be comprehensive and consistently interpreted based on the predictions of the triphasic theory.
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