Labile crosslinked hyaluronic acid via urethane formation using bis(β-isocyanatoethyl) disulphide with tuneable physicochemical and immunomodulatory properties

Here, we synthesise a new isocyanate-based crosslinker with the aim of obtaining novel tailored gels. The newly crosslinked hyaluronic acid (HA) gels were analysed in terms of rheological properties, chemical structure, swelling, biocompatibility and immunological response. Results show that the synthesised di-isocyanate out-performs other more conventional di-isocyanates due to its alkyl-based which has been shown to be slower to degrade by hydrolysis than aryl isocyanates. The alkyl-based isocyanate reacts readily with hydroxyl groups on the HA to form stable carbamate crosslinkages. Importantly and uniquely, a centrally located disulphide bond allows versatility with respect to reversible crosslinking and this allows potentially controlled layer-by-layer deposition of the HA for tailored pharmaceutical applications.