Preparation of a hyaluronic acid hydrogel through polyion complex formation using cationic polylactide-based microspheres as a biodegradable cross-linking agent

A novel hyaluronic acid (HA)-based hydrogel was prepared through polyion complex (PIC) formation between cationic polylactide (PLA)-based microspheres (MS⁺) and hyaluronic acid (HA^?) as an anionic polyelectrolyte. The MS⁺ and HA formed a biodegradable PIC hydrogel (HA^?/MS⁺) when mixed in aqueous media. The swelling behavior and mechanical properties of the PIC hydrogel could be controlled by changing the charge ratio between HA^? and MS⁺. In addition, the HA^?/MS⁺ PIC hydrogel resulted in a lower inflammatory response compared with a collagen hydrogel in vivo.