Large Variations in Resistance to Degradation between Hyaluronic Acid Viscosupplements: A Comparative Rheological Study

Abstract

Intra-articular injections of hyaluronic acid (HA) are widely used in the treatment of osteoarthritis. HA half-life varies between products which might explain differences in effectiveness between viscosupplements. Aim To compare the resistance to degradation of linear and cross-linked viscosupplements using a rheological model combining mechanical and oxidative stresses, mimicking what happens inside the joint following HA injection. Methods The rheological properties of 8 HAs were measured using a stress-imposed Rheometer DHR3. Strain sweeps were carried out to evaluate the rheological properties at rest from 0.001 to 3000% at a frequency of 1 Hz. The complex modulus G*, in Pa, and the phase tangent tan δ, dimensionless, in the linear viscoelastic domain (LVED) were extracted. The oxidation tests were conducted by exposing the product to H2O2 for 30 minutes. The effect of oxidation was evaluated by measuring variations of G* and tan δ, using an oscillation time sweep. Those tests were carried out at a frequency of 1 Hz and at 1% strain in the LVED. Results At rest, the different samples exhibited various viscous behaviors. During mixing process, G* decreased from −6.4% to −31.3%. G* of low-molecular-weight HAs decreased more than that of medium molecular weight (MW) and cross-linked products. After oxidative stress, G* variation ranged from −10.1% to −46.3%. Cross-linked HAs and those containing mannitol resisted the best to degradation. Conclusions We showed large variations in resistance to degradation between viscosupplements. The duration of effectiveness of these products deserves to be compared in randomized clinical studies.