Developing double-network (DN) hydrogels with high mechanical properties and antibacterial efficacy to combat multidrug-resistant bacterial infections and serve as scaffolds for cell culture still remains an ongoing challenge. In this study, an ion-responsive antibacterial peptide (AMP) (C-WIIIKKK, termed as IK7) was synergistically combined with a photoresponsive gelatin methacryloyl (GelMA) polymer to fabricate a biocompatible DN hydrogel. The GelMA-IK7 DN hydrogel showed enhanced mechanical properties in contrast to the individual IK7 and GelMA hydrogels and demonstrated substantial antibacterial efficacy. Further investigations revealed that the DN hydrogel effectively inhibited bacterial growth by the controlled and sustained release of the IK7 peptide. In addition, the formation of the DN hydrogel was also found to protect AMP IK7 from rapid degradation by proteinase K. Our findings suggested that the developed GelMA-IK7 DN hydrogel holds great potential for next-generation antibacterial hydrogels for three-dimensional cell culture and tissue regeneration.
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