A Carboxymethyl Chitosan Hydrogel Loaded with Bacteriophage-Derived Bacteriostatic Peptide Exhibits Antibacterial, Hemostatic, and Wound-Healing Properties

Abstract Drug-resistant bacterial infections are a formidable challenge in the treatment of skin and soft tissue wounds due to the limited efficacy of currently available antibiotics. Bacteriophage-derived antimicrobial peptides positioned as promising antibacterial agents offer a new solution to this problem. Herein, we fabricated a composite hydrogel system constructed with carboxymethyl chitosan (CMCS) containing Gp68, an antimicrobial peptide from bacteriophage PA3. The obtained CMCS@Gp68 hydrogel can protect the peptide and control the release of Gp68. The results of in vitro antibacterial assays demonstrated that the hydrogel can induce bactericidal effects on Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) through disrupting bacterial activity. The material characterization demonstrated that the mechanical properties of the hydrogel are acceptable, and the hemostatic property is rapid enough. Furthermore, the cytotoxicity assay and histopathological study also indicated that the material is biocompatible. Finally, the therapeutic effect was further studied in a rat model of full-thickness skin wound infection with P. aeruginosa. Treatment with the CMCS@Gp68 hydrogel markedly decreased bacterial burden at the wound site, suppressed inflammatory cytokine production, and promoted re-epithelialization. In summary, our multifunctional composite hydrogel with antimicrobial, hemostatic, and wound-healing properties and excellent biocompatibility is an ideal therapeutic material for infected wound treatment and regenerative medicine.