Direct visualization of lubricin-mediated enhancement of hyaluronic acid viscosity near the cartilage surface.

Abstract

Viscosupplementation is one of the most common forms of osteoarthritis (OA) therapy. It involves injecting a lubricant, typically hyaluronic acid (HA), into the joint with the goal of restoring the synovial fluid viscosity. Interestingly, the clinical performance of viscosupplements is more strongly correlated with their effective viscosity than their bulk viscosity. Effective viscosity is a mathematical construct used to reconcile a viscosupplement's material properties with its lubrication performance. Previous findings have hinted that effective viscosity is more than a theoretical concept, and may reflect a physical phenomenon mediated by lubricin at the articular surface. However, this had not yet been experimentally demonstrated. Therefore, this study: a) used microrheology to measure localized increases in the viscosity of HA near the articular surface; and b) assessed the role of lubricin in mediating this effect. To investigate this, nanoscale fluorescent beads were suspended in HA solutions, and bead Brownian motion was analyzed at various distances from the articular surface of lubricin-intact and lubricin-removed cartilage explants. This study found that HA exhibits 38 % increased viscosity at the articular surface of lubricin-intact cartilage compared to lubricin-removed cartilage, and overnight incubation in synovial fluid restored the native viscosity distribution. Elevated viscosity persisted up to 50 μm from the surface, a length-scale consistent with earlier studies. This is the first study to directly visualize localized changes in the viscosity of HA near the articular surface of cartilage resulting from lubricin-HA interactions, providing compelling evidence that effective viscosity reflects a physical phenomenon that can be measured and observed.