Kartogenin-loaded silk fibroin–chondroitin sulfate hybrid hydrogel with tailored β-sheet content: control release studies and biological activity.

Silk fibroin (SF)–chondroitin sulfate (CS)-hybrid hydrogels (HHGs) containing kartogenin (KGN) were synthesized by the induction of di-tyrosine bonds, using enzymatic crosslinking in SF/CS blend solution. Then, physical crosslinking was performed to optimize the HHG properties. The results showed that the increasing of the β-sheet content as side effect of physical crosslinking from 10% to 40% affects KGN accumulative release percentage almost three times. Biological investigations using C28/I2 human chondrocyte cell line showed that the presence of KGN, CS, and optimized β-sheets content improved cell supporting behavior of HHG. Finally, KGN loaded HHG might be a promising candidate for cartilage repair. Schematic representation of fabrication of the dual crosslinked hybrid hydrogel containing silk fibroin and chondroitin sulfate by enzymatic crosslinking and physical crosslinking method for kartogenin release. Enzymatic crosslinking: shaping di-tyrosine formation bond between silk fibroin phenol groups and locking physically chondroitin sulfate between silk fibroin β-sheets. Physical crosslinking with water and/or ethanol treatments end up in increased β-sheets content. [ABSTRACT FROM AUTHOR]