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A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability

Abstract

Despite advanced sterilization and aseptic techniques, infections associated with medical implants have not been eradicated. Most present coatings cannot simultaneously fulfil the requirements of antibacterial and antifungal activity as well as biocompatibility and reusability. Here, we report an antimicrobial hydrogel based on dimethyldecylammonium chitosan (with high quaternization)-graft-poly(ethylene glycol) methacrylate (DMDC-Q-g-EM) and poly(ethylene glycol) diacrylate, which has excellent antimicrobial efficacy against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Fusarium solani. The proposed mechanism of the antimicrobial activity of the polycationic hydrogel is by attraction of sections of anionic microbial membrane into the internal nanopores of the hydrogel, like an ‘anion sponge’, leading to microbial membrane disruption and then microbe death. We have also demonstrated a thin uniform adherent coating of the hydrogel by simple ultraviolet immobilization. An animal study shows that DMDC-Q-g-EM hydrogel coating is biocompatible with rabbit conjunctiva and has no toxicity to the epithelial cells or the underlying stroma.

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Figure 1: qC-g-EM polymers and the antimicrobial killing mechanism of their hydrogels.
Figure 2: Antimicrobial activities of qC-g-EM hydrogels against various bacteria and fungi.
Figure 3: Coating of DMDC-Q-g-EM hydrogel on fluoropolymer substrate.
Figure 4: In vitro and in vivo biocompatibility studies.

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Acknowledgements

This work was funded and supported by Menicon Holdings (Japan), a Singapore Ministry of Education Tier 2 grant (M45120007), Nanyang Technological University (Singapore) and a Singapore SingHealth Foundation grant (SHF/09/GMC(1)/012(R) (R705)). R.W.B. and H-Y.Z. were supported by NMRC/TCR/002-SERI/2008 R618. Y.C. was supported by SingHealth Foundation SHF/09/GMC(1)/012(R) (R705). W.L. and Y.M. were supported by a Singapore Ministry of Education Tier 2 grant (T206B3210RS). We acknowledge the Singapore General Hospital (Pathology Department) for carrying out some of the early antimicrobial tests. We thank Y. Shucong, W. Xiujuan and F. Ning for their help in using field emission scanning electron microscopy, scanning electron microscopy and atomic force microscopy. The provision of computation time from the NTU HPC centre is gratefully acknowledged.

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Contributions

P.L. carried out the testing and coating experiments. Y.F.P., P.L. and S.H.Y. did the syntheses and characterization of all the polymers. Y.C. carried out the in vitro biocompatibility studies. X.Q. carried out some early antimicrobial testing. W.L. and Y.M. did the computer simulation and related writing. H-Y.Z. and R.W.B. did the animal study and related writing. C.Z., E-T.K., M.L., M.W.C., S.S.J.L., C.M.L. and M.B.C-P. advised on the design and interpretation of the experiments. M.B.C-P. directed the overall project. P.L., Y.F.P. and M.B.C-P. did the main writing of the manuscript.

Corresponding author

Correspondence to Mary B. Chan-Park.

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Competing interests

M.B.C-P. was the PI of this project funded by Menicon, which was directly interested in this product.

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Li, P., Poon, Y., Li, W. et al. A polycationic antimicrobial and biocompatible hydrogel with microbe membrane suctioning ability. Nature Mater 10, 149–156 (2011). https://doi.org/10.1038/nmat2915

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