Abstract
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.
Highlights
Crosslinking reactions involving hyaluronic acid (HA) have often been used to create a polymer network with high stiffness and low susceptibility to enzymatic degradation.[1]
We studied the influence of the size of HA microparticles at a 1/1 HA/divinyl sulfone (DVS) mass ratio on the swelling, rheological properties and extrusion force.[14]
The HA crosslinked with DVS (HA-DVS) microparticles were weighed after swelling, and the weight of the dry gels was determined by drying the gel under vacuum (1 mm Hg) at 25 oC for 3 days, according to the methods published by Shu et al.[22]
Summary
Crosslinking reactions involving hyaluronic acid (HA) have often been used to create a polymer network with high stiffness and low susceptibility to enzymatic degradation.[1]. Balazs and Leschchiner[16] described the effects of the extension of the crosslinking of HA-DVS on the swelling of HA-DVS gel particles, as controlled by factors such as the HA molecular weight, the HA/DVS mass ratio and the concentrations of HA, alkali and neutral salts. Alkali concentrations of 0.2 and 0.01 mol L-1 were studied for a HA/DVS ratio of 5/1 At this ratio, the swelling decreased with increasing pH, indicating a higher crosslinking degree. The results showed alkaline control in the narrow pH range from 11.79 to 12.63, which can serve to fine-tune the HA‐DVS crosslinking degree These changes, combined with the HA/DVS ratio, may produce softer microparticles that do not require mixture with fluid non‐crosslinked HA for injection in humans, or they may increase the crosslinking degree at lower concentrations of DVS. All other reagents were purchased from Synth® (Diadema, SP, Brazil) unless otherwise specified
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