Functionalization of hyaluronic acid for development of self-healing hydrogels for biomedical applications: A review

Materials that are capable of undergoing self-repair following any physical damage or rupture due to external stimuli are identified as self-healing materials. Such materials are engineered by crosslinking the polymer backbone chains typically through reversible linkages. These reversible linkages include imines, metal-ligand coordination, polyelectrolyte interaction, disulfide, etc. These bonds are reversibly responsive to changes in various stimuli. Newer self-healing materials are now being developed in the field of biomedicine. Chitosan, cellulose, starch etc. are a few examples of polysaccharides that are generally used to synthesize such materials. Hyaluronic acid has been a very recent addition to the list of polysaccharides that are being investigated for construction of self-healing materials. It is non-toxic, non-immunogenic, has good gelation property and good injectability. Hyaluronic acid based self-healing materials are particularly employed for targeted drug delivery, protein and cell delivery, electronics, biosensors and many such biomedical applications. This review critically focuses on the functionalization of hyaluronic acid to fabricate self-healing hydrogels for biomedical applications. It also explores and sums up the mechanical data as well as self-healing efficiency of the hydrogels across wide range of interactions as discussed in the review below.