One-Pot Synthesis of Dual Functionalised Hyaluronic Acid for Tuneable and Adhesive Double Crosslinked Hydrogel Networks

Routine techniques to close wounds such as sutures and staples have significant drawbacks which can negatively impact wound recovery. Whilst sutures and staples have high tensile strength, they are time consuming to administer, require high surgical skill, create additional damage to the wound environment, can allow for bacterial infiltration and do not completely prevent fluid ingress and egress. Tissue adhesives have been studied for many decades as potential replacements of sutures but poor adhesion, mechanical properties, and biocompatibility precludes many system’s translation to clinic. Although there are commercially available products e.g. Evicel, BioGlue, and ReSure, most have critical compromises that limits their efficacy. In this work, an aldehyde and methacrylate functionalised Hyaluronic acid (HA) biopolymer (HA-MA-CHO) has been synthesised for use in a novel, adhesive, biocompatible and biodegradable double crosslinked hydrogel network (DCN) for the effective closure and sealing of wounds. Aldehyde (CHO) groups are able to bond with native proteins on the tissue surface and act as a crosslinking site by reacting with the disulphide containing crosslinker 3,3’-dithiobis(propanoic hydrazide) (DTPH), forming a single crosslinked soft hydrogel network (SCN) with shear-thinning and self healing properties. The gel can then be further cured and strengthened with rapid UV-photopolymerization of the methacrylate groups to create a DCN. This two stage gelation and administration process of the hydrogel allows for easy in-situ application of UV crosslink-able pre-hydrogel solutions. This DCN hydrogel shows remarkable versatility as the storage modulus (G’) has shown to be highly tuneable (10³ – 10⁵ Pa) by varying polymer concentrations, degrees of methacrylate substitutions and HA-MA-CHO:DTPH molar ratios to allow for application to many different wound environments. The hydrogel prepared showed high adhesion to porcine skin surpassing a burst pressure result for the commercially available tissue adhesive BioGlue by 52%. Along with these properties the DCN hydrogels also showed excellent cell viability.