In vitro and ex vivo evaluation of the rheological properties, tribological performance, and oxidative stability of cellulose nanocrystal–enhanced hyaluronic acid suspensions as potential viscosupplements

Osteoarthritis (OA) is characterized by progressive cartilage degeneration accompanied by elevated levels of reactive oxygen species (ROS). ROS accelerates the oxidative degradation of hyaluronic acid (HA) and compromises the lubricating function of synovial fluid (SF). Although commercial HA-based viscosupplements provide symptomatic relief, their functional longevity is limited under oxidative joint environments. This study investigates HA-based cellulose nanocrystal (CNC) suspensions as potential viscosupplement formulations with enhanced oxidative stability and rheological and tribological performance. The optimized HA/CNC formulation exhibited increased resistance to oxidative degradation and an apparent DPPH radical-scavenging rate constant approximately one order of magnitude higher than that of MonoVisc. This stabilization was accompanied by solid-like viscoelastic behavior for the HA/CNC formulation, in contrast to the predominantly liquid-like response of MonoVisc. Importantly, when combined with SF collected from OA patients undergoing total knee replacement surgery, the HA/CNC suspension enhanced viscoelastic properties and retained rheological characteristics after 7 months of storage at −20 °C under controlled ex vivo conditions. Tribological evaluation revealed sustained lubrication with a reduced friction coefficient compared with MonoVisc. Preliminary in vitro cytocompatibility assessment showed no acute cytotoxicity and no detectable TNF-α release under the tested conditions. These results demonstrate that CNC incorporation enhances the oxidative stability, viscoelastic response, and lubrication performance of HA-based formulations, supporting their potential as candidate viscosupplements under controlled in vitro and ex vivo conditions.