Dextran and peptide-based pH-sensitive hydrogel boosts healing process in multidrug-resistant bacteria-infected wounds

Carbohydr Polym. 2022 Feb 15:278:118994. doi: 10.1016/j.carbpol.2021.118994. Epub 2021 Dec 10.

Abstract

Traumatic multidrug-resistant (MDR) bacterial infections are deadly threat to the public. To combat MDR bacteria, we developed a dual functional pH-sensitive hydrogel based on peptide DP7 (VQWRIRVAVIRK) and oxidized dextran (DP7-ODEX hydrogel). As an antimicrobial peptide, DP7 can synergize with many antibiotics; thus, we loaded ceftazidime into DP7-ODEX hydrogel, which showed an obvious advantage in MDR P. aeruginosa inhibition. Additionally, due to the interaction between aldehyde groups in oxidized dextran and amine groups from wound tissue, the hydrogel could extend on the irregular surface of skin defects and promote epithelial cells adhesion. DP7 could also be used as a wound-healing peptide and accelerate the healing process. We confirmed that the DP7-ODEX hydrogel exerted formidable therapeutic effects in normal or diabetic wound infection model. According to histomorphology analysis we found that DP7 hydrogel also have a scarless wound healing ability. In summary, we developed a hydrogel fabricated by the dual functional peptide DP7 that can kill multidrug-resistant bacteria colonizing the wound bed and boost scarless wound healing.

Keywords: Antibacterial peptide; DP7; Dextran; MDR bacteria; Wound healing.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Movement / drug effects
  • Cells, Cultured
  • Dextrans / chemistry
  • Dextrans / pharmacology*
  • Drug Liberation
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Escherichia coli / drug effects
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Hydrogen-Ion Concentration
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • NIH 3T3 Cells
  • Particle Size
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Pseudomonas aeruginosa / drug effects
  • Staphylococcus aureus / drug effects
  • Wound Infection / drug therapy*
  • Wound Infection / microbiology

Substances

  • Anti-Bacterial Agents
  • Dextrans
  • Hydrogels
  • Peptides