Effective Strategies for Developing Potent, Broad-Spectrum Antibacterial and Wound Healing Promotion from Short-Chain Antimicrobial Peptides

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Abstract

Traumatic multidrug resistant bacterial infections are the most lethal threat to wound healing. Antimicrobial peptides have been widely used in the antimicrobial field for their good biocompatibility and resistance to multidrug-resistant bacteria. In this work, bacterial membranes of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were extracted and immobilized on homemade silica microspheres to make a bacterial membrane chromatography stationary phase in order to quickly screen for peptides with antibacterial effects. The antimicrobial peptide was then successfully screened using bacterial membrane chromatography from a library of peptides synthesized by the one-bead-one-compound method. The antimicrobial peptide was effective in better shielding both Gram-positive and Gram-negative bacteria. Based on this antimicrobial peptide (RWPIL), we have developed an antimicrobial hydrogel with a backbone of this antimicrobial peptide and oxidized dextran (ODEX). Owing to the interlinkage between the aldehyde group in oxidized dextran and the amine group from the trauma tissue, the hydrogel extends over the irregular obverse of the skin defect and promotes epithelial cell adhesion. Based on the histomorphological analysis, we confirmed that the RWPIL–ODEX hydrogel exerts a powerful therapeutic effect in a wound infection model. In conclusion, we have developed a new antimicrobial peptide, RWPIL, and a hydrogel based on the peptide that kills multidrug-resistant bacteria parasitic on wounds and promotes wound healing.

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