Silk acid-tyramine Hydrogels with Rapid Gelation Properties for 3D Cell Culture

Silk fibroin (SF) can be enzymatically crosslinked through tyrosine residues to fabricate hydrogels with good biocompatibility and tunable mechanical properties. Using tyramine substitution can increase the phenolic group content to facilitate the gelation kinetics and mechanical properties. In this study, a two-step chemical modification method is demonstrated to synthesize silk acid-tyramine (SA-TA) conjugates with a high phenolic group content (>7 mol%). The SA-TA shows rapid enzyme-catalyzed gelation property where the sol-gel transition takes less than 10 s at 37°C, allowing cell encapsulation with uniform distribution while maintaining high cell viability (>90%). Furthermore, the enzyme-catalyzed SA-TA hydrogels show enhanced storage modulus than enzyme-catalyzed SF hydrogels, long-term stability, and good cytocompatibility, indicating their great potential in 3D cell culture. The in vivo implantation study demonstrates that the SA-TA hydrogels are biodegradable with a mild immune response. This implies that SA-TA hydrogels can be applied in various medical applications, such as tissue engineering, cell delivery, and 3D bioprinting. Statement of Significance In this study, a two-step chemical modification method is demonstrated to synthesize silk acid-tyramine (SA-TA) conjugates with a high phenolic group content (>7 mol%). Owing to the increased content of the phenolic group, the SA-TA shows rapid enzyme-catalyzed gelation property where the sol-gel transition takes less than 10 s at 37°C, allowing cell encapsulation with uniform distribution while maintaining high cell viability (>90%). Furthermore, the enzyme-catalyzed SA-TA hydrogels show enhanced storage modulus than enzyme-catalyzed SF hydrogels, long-term stability, and good cytocompatibility, indicating their great potential in 3D cell culture. The in vivo implantation study demonstrates that the SA-TA hydrogels are biodegradable with a mild immune response. This implies that SA-TA hydrogels can be applied in various medical applications, such as tissue engineering, cell delivery, and 3D bioprinting.