Efficient Regulation of the Behaviors of Silk Fibroin Hydrogel via Enzyme-Catalyzed Coupling of Hyaluronic Acid

Pure silk fibroin (SF) hydrogel exhibits poor elasticity and low water retention ability, owing to the compact crystalline structure and high content of hydrophobic amino acids. Herein, a composite double-network hydrogel of SF and tyramine-modified hyaluronic acid (mHA) was constructed, via the laccase-catalyzed coupling reactions between the phenolic hydroxyl groups from SF and mHA chains. The obtained hydrogel exhibits improved structural stability and flexibility compared to pure SF hydrogel. Meanwhile, the swelling ratio, mechanical property, drug loading, and release behaviors can be readily regulated by alcoholization, altering pH value, and ionic strength of soaking solutions. Increasing pH values promoted the swelling capacity of SF/mHA hydrogel, resulting in an efficient loading of cationic drugs and sustained release of anionic drugs as well. The addition of inorganic salts reduced electrostatic repulsion in the hydrogel scaffold, accompanying with a noticeable improvement of toughness. Furthermore, alcohol treatment induced conformation changes of fibroin protein, and the composite hydrogel achieved a higher fracture and improved elasticity. The present work provides a biological alternative to regulate the mechanical behavior, drug loading, and sustained release capacity of the SF-based hydrogel.