UC San Diego

In normal joints, tissues such as synovium and articular cartilage provide resistance to outflow of water and macromolecules in synovial fluid (SF). Hyaluronan (HA) normally contributes to hydraulic outflow resistance under increased pressure by a reduction of the driving force via a concentration polarized layer at the surfaces of the joint capsule [11, 44, 58, 66]. Changes in the synovial joint that occur in osteoarthritis (OA) and injury, including decreased HA content and joint tissue degeneration, are likely to alter the formation of this layer. An ultrafiltration model was solved to evaluate the dynamics and steady-state properties of HA concentration polarization across the synovium in health and disease, and the model was validated by comparing results to experimental data. Validation simulations were similar to measured transient and steady-state values for concentration and retention. The model predicted that HA at a normal concentration and molecular weight is mostly retained, resulting in physiologically observed intra- articular pressures. Predicted HA retention, concentration distributions, and dynamic hydraulic permeability were altered with decreased initial HA concentration and molecular weight, as observed in disease. In diseased joints, after a period of temporary slight concentration polarization, HA is predicted to be depleted from the joint cavity due to steady loss through the membrane. These studies extend current understanding of hyaluronic acid concentration polarization in the normal and diseased synovial joint by modeling flow of HA solutions through a membrane, as well as the effect of HA concentration and retention on the formation of the concentration polarization layer