Modification and crosslinking strategies for hyaluronic acid-based hydrogel biomaterials

Hyaluronic acid (HA) is an attractive extracellular matrix-derived polymer. The related HA-based hydrogels are emerging to be the hotspots in the cutting edge of biomaterials. The continuous sights concentrate on exploring modification methods and crosslinking strategies to promote the advancement of HA-based hydrogels with enhanced physical/chemical properties and enriched biological performance. Here, the advances on modification methods and crosslinking strategies for fabricating HA-based hydrogels with diverse capacities are summarized. Firstly, the modification reactions that occur on the active hydroxyl, carboxyl and N-acetyl groups of HA molecule are discussed. Next, the emphasis is put on various crosslinking strategies including physical crosslinking, covalent crosslinking and dynamic covalent crosslinking. Finally, we provide a general summary and give a critical viewpoint on the remaining challenges and the future development of HA-based hydrogels. It is hoped that this review can provide new proposals for the specific design of functional hydrogel biomaterials.