A novel oxido-viscosifying Hyaluronic Acid-antioxidant conjugate for osteoarthritis therapy: Biocompatibility assessments

• Improved hyaluron formulation for osteoarthritis.
• Conjugation of antioxidants on HA backbone.
• Presenting a novel strategy for protect HA from degradation.
• Proving the biocompatibility of the novel formulation in vivo.
• 1st report on a novel “oxido-viscosifying effect”.

To overcome the problem of fast degradation of Hyaluronic Acid (HA) in the treatment of osteoarthritis (OA), HA was protected against the oxidative stress generated by the pathology. Antioxidant conjugated HAs were synthesized and tested in vitro for their resistance in an oxidative environment mimicking OA. HA-4-aminoresorcinol (HA-4AR) displayed the interesting property of increasing in viscosity under oxidative conditions because of crosslinking induced by electron transfer. The novel HA polymer conjugate was shown to be biocompatible in vitro on fibroblast-like synoviocytes extracted from an arthritic patient. This HA conjugate was also assessed in vivo by intra-articular injection in healthy rabbits and was found to be comparable to the native polymer in terms of biocompatibility. This study suggests that HA-4AR is a promising candidate for a next generation viscosupplementation formulation.

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