Micro-Rheology of an Articular Viscosupplement for Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA) is a widespread joint disease that affects people across a wide range of ages. In RA, the viscoelastic properties of synovial fluid (SF) are significantly compromised, reducing its ability to protect cartilage surfaces during joint movements. Importantly, unlike osteoarthritis, hyaluronic acid (HA) viscosupplements are not effective for the treatment of RA, as they are prone to degradation in the lactic acid environment of RA-affected joints. Therefore, it is crucial to develop viscosupplements that can maintain viscoelastic properties in joints with elevated lactic acid levels. In the present study, we explore the microrheology of mucin-blended HA to maintain viscoelasticity in a simulated RA environment. The study reveals that the mucin-blended hyaluronic acid does not phase separate at higher lactic acid levels and is able to retain the required viscous and elastic behaviors as compared to a pure HA solution. Additionally, a morphological study using atomic force microscopy reveals that the addition of mucin to HA creates a fiber-bundle-like structure, which resists deformation under shear, in contrast to the fiber-like morphologies of pure HA that deform more readily. Furthermore, an interfacial microrheological study using a confocal laser scanning microscope reveals that mucin-blended HA exhibits reduced viscoelastic behavior at the collagen interface compared with pristine HA, suggesting potential boundary lubrication by reducing interactions between HA and the cartilage surface.