Antibacterial peptide NZ2114-loaded hydrogel accelerates Staphylococcus aureus-infected wound healing

Wound infection caused by Staphylococcus aureus (S. aureus) is a great challenge which has caused significant burden and economic loss to the medical system. NZ2114, a plectasin-derived peptide, is an antibacterial agent for preventing and treating S. aureus infection, especially for methicillin-resistant S. aureus (MRSA) infection. Here, three-dimensional reticulated antimicrobial peptide (AMP) NZ2114 hydrogels were developed based on hydroxypropyl cellulose (HPC) and sodium alginate (SA); they displayed sustained and stable release properties (97.88 ± 1.79% and 91.1 ± 10.52% release rate in 72 h, respectively) and good short-term cytocompatibility and hemocompatibility. But the HPC-NZ2114 hydrogel had a smaller pore size (diameter 0.832 ± 0.420 μm vs. 3.912 ± 2.881 μm) and better mechanical properties than that of the SA-NZ2114 hydrogel. HPC/SA-NZ2114 hydrogels possess efficient antimicrobial activity in vitro and in vivo. In a full-thickness skin defect model, the wound closure of the 1.024 mg/g HPC-NZ2114 hydrogel group was superior to those of the SA-NZ2114 hydrogel and antibiotic groups on day 7. The HPC-NZ2114 hydrogel accelerated wound healing by reducing inflammation and promoting the production of vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and angiogenesis (CD31) through histological and immunohistochemistry evaluation. These data indicated that the HPC-NZ2114 hydrogel is an excellent candidate for S. aureus infection wound dressing. KEY POINTS: •NZ2114 hydrogels showed potential in vitro bactericidal activity against S. aureus •NZ2114 hydrogels could release continuously for 72 h and had good biocompatibility •NZ2114 hydrogels could effectively promote S. aureus-infected wound healing.