The Performance of Crosslinking with Divinyl Sulfone as Controlled by the Interplay Between the Chemical Modification and Conformation of Hyaluronic Acid

Hyaluronic acid (HA) microparticles crosslinked with divinyl sulfone (DVS) are primarily used in viscosupplementation to restore the viscoelastic properties of synovial fluid in the treatment of joint diseases. The crosslinking degree provides the swelling and rheological properties required for injectable application and biological stability. In this work, we studied the effects of alkaline medium on the crosslinking performance between HA and DVS. The crosslinking degree was evaluated based on the modification of the swelling and rheological properties of HA microparticles crosslinked at 1/1 HA/DVS mass ratio. Stable microparticles were obtained by shearing in the narrow pH range of 11.79 to 12.63. The microparticles exhibited gel-like dynamic mechanical behavior in the frequency range examined. Alkalinity increased the swelling and decreased the viscoelasticity of the HA microparticles. Ultimately, the interplay between the chemical modification and conformation of HA chains may control viscoelasticity and swelling at the levels required for specific applications.