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

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Abstract

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

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Data availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

We acknowledge Chunli Li from the Core Facility at the Institute of Microbiology at the Chinese Academy of Sciences (CAS) for the technical support with SEM.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 31872393), the Key Projects of Alternatives to Antibiotic for Animal (Grant No. CAAS-ZDRW202111), and Feed (Grant No. CAAS-ZDXT2018008) Usages of the Agricultural Science and Technology Innovation Program (ASTIP).

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Authors and Affiliations

  1. School of Environmental Ecology and Biological Engineering, Wuhan Institute of Technology – WIT, Wuhan, People’s Republic of China

    Yan Huang & Lingyun Wei

  2. Innovative Team of Antimicrobial Peptides and Alternatives to Antibiotics, and Gene Engineering Laboratory, Feed Research Institute, Chinese Academy of Agricultural Sciences, Haidian District, 12 Zhongguancun Nandajie St, Beijing, 100081, People’s Republic of China

    Yan Huang, Na Yang, Da Teng, Ruoyu Mao, Ya Hao, Xuanxuan Ma & Jianhua Wang

  3. Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing, 100081, People’s Republic of China

    Yan Huang, Na Yang, Da Teng, Ruoyu Mao, Ya Hao, Xuanxuan Ma & Jianhua Wang

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  1. Yan Huang
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  2. Na Yang
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  3. Da Teng
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  8. Jianhua Wang
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Contributions

JW and NY conceived and designed the study; YH carried out all experiments. YH and DT conducted the data analysis; YH wrote the first draft; RM, XM, and LW contributed to the writing, review, and editing of the manuscript. All the authors gave final approval. JW contributed in funding acquisition. YH contributed to materials and reagents.

Corresponding authors

Correspondence to Na Yang, Lingyun Wei or Jianhua Wang.

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The mouse experiment was performed according to the Animal Care and Use Committee of the Feed Research Institute of the Chinese Academy of Agricultural Sciences (CAAS) and approved by the Laboratory Animal Ethical Committee and its Inspection of the Feed Research Institute of CAAS (AEC-CAAS-20090609).

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Huang, Y., Yang, N., Teng, D. et al. Antibacterial peptide NZ2114-loaded hydrogel accelerates Staphylococcus aureus-infected wound healing. Appl Microbiol Biotechnol 106, 3639–3656 (2022). https://doi.org/10.1007/s00253-022-11943-w

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