A COMPARISON STUDY OF THE EFFECT OF NOVEL HYALURONIC ACID (HA) BASED THERAPEUTIC LUBRICANTS ON FRICTION LEVELS OF OSTEOARTHRITIC DAMAGED HUMAN CARTILAGE

Background: Injectable therapeutic lubricants have been recently introduced as a treatment for osteoarthritis (OA) in the knee. Currently their formulation is based upon different molecular weights of HA. The lubricants are used in viscosupplementation therapies which replenish the synovial fluid (SF) in an attempt to reduce pain and increase joint mobility. Although current formulations used in three or five weekly injection courses have shown reduced joint pain and improved mobility [1] their mechanism of action is contentious and pain relief lasts for a limited period. This has previously led to scepticism over these products as a viable treatment for OA [2]. Recent work [3,4] has indicated that boundary lubrication is an important mechanism of action associated with HA treatment under OA conditions. The current study focused on this mechanism and compared two novel lubricants, diphosphatidylcholine (DPPC) and a mixture of HA and DPPC, with a commercially available hyaluronic acid formulation, Arthrease®, in terms of their effect on the friction coefficient of human cartilage under boundary lubricating conditions.Objectives: To identify a novel lubricant formulation that will effectively decrease friction between human osteoarthritic cartilage surfaces.Methods: The effects of the different lubricant formulations were tested using a human cartilage model. This model used a specialized friction rig, designed for pin on plate testing. Samples consisted of tibial plateau (explanted at total knee replacement) and cartilage pins taken from femoral heads (explanted following fractured neck of femur operations). 10mm by 5mm flat areas were treated with lubricant for 24 hours. The plateau and the pin were mounted in the test rig and a 25 Newton load was applied for a period of 10 minutes. The cartilage pin was then slid across the plateau cartilage surface at a speed of 4mm/sec for approximately 3 seconds to allow full contact over the test area. Start up friction co-efficients were recorded through measurement of the peak load. Each test consisted of a primary test of five repeats in Ringer's solution followed by a secondary test of five repeats in the test lubricant. Ringer's was used as a standard as previous work by Forster et al [5], showed that it produced similar friction co-efficients to SF. The test groups included Arthrease® (10mg/ml HA in phosphate buffered saline (PBS), M.W. = 3.0 MDa), DPPC liposomes (200mg/ml in PBS), and HA/DPPC mixture (5mg/ml HA in PBS, 100mg/ml DPPC liposomes in PBS) and a Ringers control.Results: Results showed that all three of the test lubricants showed reduced friction co-efficients compared to the Ringer's control. The Arthrease and DPPC lubricants produced a mean reduction in friction of 47.2% and 46.5% respectively. The HA/DPPC mixture demonstrated a mean reduction of friction of 69.5%. Statistical analysis showed that all the test lubricants were highly significantly different (P=0.01) when compared to the Ringer's control. There was no statistically significant difference between the three lubricant groups, probably due to the high degree of sample variability.Conclusion: The results confirm that both HA and DPPC promote boundary lubrication between cartilage surfaces, even under osteoarthritic conditions. Combinations of HA and DPPC produced a greater mean decrease in cartilage friction when compared to Arthrease®and DPPC lubricants alone. These results are very encouraging for the future formulations of HA/DPPC which will use different concentrations of the individual components.1. Thompson, J.I., Y.W. Huang, et al. (2002). Osteoarthritis Cartilage 10A: 70-71.; 2. Brandt, K.D., G.N. Smith, Jr., et al. (2000). Arthritis Rheum 43(6): 1192-203; 3. Mori, S., M. Naito, et al. (2002). Int Orthop 26: 116-121.; 4. Bell, C.J, J. Fisher, E. Ingham, R. Forsey, J.I Thompson, M.H. Stone (2002). Trnas Orthop Res Soc: 676; 5. Forster, H. and J. Fisher (1996). Proceedings form the Institute of Mechanical Engineers 210: 109-119.Citation: , volume , supplement , year 2003, page Session: Osteoarthritis – Clinical aspects and treatment