Self-healing hyaluronic acid hydrogels based on dynamic Schiff base linkages as biomaterials

Abstract Natural hydrogels are widely investigated for biomedical applications because of their structures similar to extracellular matrix of native tissues, possessing excellent biocompatibility and biodegradability. However, they are often susceptible to mechanical disruption. In this study, self-healing hyaluronic acid (HA) hydrogels are fabricated through a facile dynamic covalent Schiff base reaction. Dialdehyde-modified HA (AHA) precursor was synthesized, and then the AHA/cystamine dihydrochloride (AHA/Cys) hydrogels were formed by blending AHA and Cys at acidic pH levels. By varying Cys to AHA ratio, the hydrogel morphology, swelling and kinetics of gelation could be controlled. Gelation occurred fast, which was predominantly attributed to Schiff base reaction between the dialdehyde groups on AHA and amimo groups on Cys. The hydrogel exhibited improved mechanical properties with increase in Cys content. Furthermore, due to dynamic imine bonds, this hydrogel demonstrated excellent self-healing ability based on the stress after mechanical disruption. Also, it was found to be pH-responsive and injectable. Taken together, this kind of hyaluronic acid hydrogel can provide promising future for various biomedical applications in drug delivery, bioprinting, smart robots and tissue regeneration.