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Burns Trauma. 2018 May 21;6:16. doi: 10.1186/s41038-018-0115-2. eCollection 2018.

Synthesis of graphene oxide-quaternary ammonium nanocomposite with synergistic antibacterial activity to promote infected wound healing.

Liu T#1,2, Liu Y#3, Liu M1,2, Wang Y1,2, He W1,2, Shi G1,2, Hu X1,2, Zhan R1,2, Luo G1,2, Xing M1,3, Wu J1,4.

Author information

1
1Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University, Chongqing, China.
2
Chongqing Key Laboratory for Disease Proteomics, Chongqing, China.
3
3Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB Canada.
4
4Department of Burns, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
#
Contributed equally

Abstract

Background:

Bacterial infection is one of the most common complications in burn, trauma, and chronic refractory wounds and is an impediment to healing. The frequent occurrence of antimicrobial-resistant bacteria due to irrational application of antibiotics increases treatment cost and mortality. Graphene oxide (GO) has been generally reported to possess high antimicrobial activity against a wide range of bacteria in vitro. In this study, a graphene oxide-quaternary ammonium salt (GO-QAS) nanocomposite was synthesized and thoroughly investigated for synergistic antibacterial activity, underlying antibacterial mechanisms and biocompatibility in vitro and in vivo.

Methods:

The GO-QAS nanocomposite was synthesized through amidation reactions of carboxylic group end-capped QAS polymers with primary amine-decorated GO to achieve high QAS loading ratios on nanosheets. Next, we investigated the antibacterial activity and biocompatibility of GO-QAS in vitro and in vivo.

Results:

GO-QAS exhibited synergistic antibacterial activity against bacteria through not only mechanical membrane perturbation, including wrapping, bacterial membrane insertion, and bacterial membrane perforation, but also oxidative stress induction. In addition, it was found that GO-QAS could eradicate multidrug-resistant bacteria more effectively than conventional antibiotics. The in vitro and in vivo toxicity tests indicated that GO-QAS did not exhibit obvious toxicity towards mammalian cells or organs at low concentrations. Notably, GO-QAS topically applied on infected wounds maintained highly efficient antibacterial activity and promoted infected wound healing in vivo.

Conclusions:

The GO-QAS nanocomposite exhibits excellent synergistic antibacterial activity and good biocompatibility both in vitro and in vivo. The antibacterial mechanisms involve both mechanical membrane perturbation and oxidative stress induction. In addition, GO-QAS accelerated the healing process of infected wounds by promoting re-epithelialization and granulation tissue formation. Overall, the results indicated that the GO-QAS nanocomposite could be applied as a promising antimicrobial agent for infected wound management and antibacterial wound dressing synthesis.

KEYWORDS:

Antibacterial activity; Antibiotic resistance; Graphene oxide; Quaternary ammonium salt; Synergistic effect; Wound healing

Conflict of interest statement

All the animal experiments (including in vivo biosafety, antibacterial activity, and infected wound healing evaluation) and the hemolysis assay were approved by the Institutional Animal Care and Use Committee of the Army Medical University.The authors declare that they have no competing interests.

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