Ultrabroad-spectrum, multidrug resistant bacteria-killing, and biocompatible quaternized chitin derivative for infected wound healing

Abstract

Wound infections have consistently been recognized as serious threats to human. The design of antimicrobial and biocompatible wound dressings for infected wounds is an area of constant research. Herein, we homogeneously synthesized an ultrabroad-spectrum antimicrobial and biocompatible quaternized chitin derivative (QC-4) in a high-efficiency and sustainable route using aqueous KOH/urea solution. Particularly, QC-4 displayed powerful multidrug resistant bacteria-killing activities even at a very low antimicrobial concentration range from 500 ng/mL to 5 μg/mL, including clinically prevalent multidrug-resistant Escherichia coli (MDR-E. coli), methicillin resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (MRPA), and multidrug-resistant Acinetobacter baumannii (MDR-A. baumannii). With the aim to facilitate clinical translation, we validated the biocompatibility and safety of QC-4 both in vitro and in vivo, and further assessed the effects of QC-4 on infected wound healing in a porcine infectious full-thickness skin wound model. QC-4 demonstrated significant reduction of microbial aggregates and enhanced wound-healing effects by promoted re-epithelialization and collagen deposition, which were quite comparable to that of commercial Alginate-Ag dressing and absolutely superior to commercial Chitoclot Bandage dressing. Additionally, we provided clear evidences that QC-4 had a unique mechanism of action by attracting electrostatically to the negatively charged microbial surface, thus damaging the microbial cell wall and membrane. Findings of this work provided robust preclinical rationale for the future translational applications of QC-4 as a novel ultrabroad-spectrum and multidrug resistant bacteria-killing antimicrobial wound dressing for clinical wound management.