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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Hetrick, E. M. & Schoenfisch, M. H. Reducing implant-related infections: Active release strategies. Chem. Soc. Rev. 35, 780–789 (2006).
Ferreira, L. & Zumbuehl, A. Non-leaching surfaces capable of killing microorganisms on contact. J. Mater. Chem. 19, 7796–7806 (2009).
Klibanov, A. M. Permanently microbicidal materials coatings. J. Mater. Chem. 17, 2479–2482 (2007).
Kristinsson, K. G. et al. Antimicrobial activity of polymers coated with iodine-complexed polyvinylpyrrolidone. J. Biomater. Appl. 5, 173–184 (1991).
Smith, A. W. Biofilms and antibiotic therapy: Is there a role for combating bacterial resistance by the use of novel drug delivery systems. Adv. Drug Delivery Rev. 57, 1539–1550 (2005).
Milovic, N. M., Wang, J., Lewis, K. & Klibanov, A. M. Immobilized N-alkylated polyethylenimine avidly kills bacteria by rupturing cell membranes with no resistance developed. Biotechnol. Bioeng. 90, 715–722 (2005).
Lin, J., Qiu, S. Y., Lewis, K. & Klibanov, A. M. Bactericidal properties of flat surfaces and nanoparticles derivatized with alkylated polyethylenimines. Biotechnol. Prog. 18, 1082–1086 (2002).
Tiller, J. C., Liao, C. J., Lewis, K. & Klibanov, A. M. Designing surfaces that kill bacteria on contact. Proc. Natl Acad. Sci. USA 98, 5981–5985 (2001).
Ilker, M. F., Nusslein, K., Tew, G. N. & Coughlin, E. B. Tuning the hemolytic and antibacterial activities of amphiphilic polynorbornene derivatives. J. Am. Chem. Soc. 126, 15870–15875 (2004).
Kuroda, K. & DeGrado, W. F. Amphiphilic polymethacrylate derivatives as antimicrobial agents. J. Am. Chem. Soc. 127, 4128–4129 (2005).
Tew, G. N., Clements, D., Tang, H., Arnt, L. & Scott, R. W. Antimicrobial activity of an abiotic host defense peptide mimic. Biochim. Biophys. Acta 1758, 1387–1392 (2006).
Gabriel, G. J., Som, A., Madkour, A. E., Eren, T. & Tew, G. N. Infectious disease: Connecting innate immunity to biocidal polymers. Mater. Sci. Eng. R 57, 28–64 (2007).
Kenawy, E. R., Worley, S. D. & Broughton, R. The chemistry and applications of antimicrobial polymers: A state-of-the-art review. Biomacromolecules 8, 1359–1384 (2007).
Bagheri, M., Beyermann, M. & Dathe, M. Immobilization reduces the activity of surface-bound cationic antimicrobial peptides with no influence upon the activity spectrum. Antimicrob. Agents Chemother. 53, 1132–1141 (2009).
Imazato, S., Russell, R. R. B. & McCabe, J. F. Antibacterial activity of MDPB polymer incorporated in dental resin. J. Dent. 23, 177–181 (1995).
Sambhy, V., Peterson, B. R. & Sen, A. Antibacterial and hemolytic activities of pyridinium polymers as a function of the spatial relationship between the positive charge and the pendant alkyl tail. Angew. Chem. Int. Ed. 47, 1250–1254 (2008).
Stratton, T. R., Rickus, J. L. & Youngblood, J. In vitro biocompatibility studies of antibacterial quaternary polymers. Biomacromolecules 10, 2550–2555 (2009).
Zumbuehl, A. et al. Antifungal hydrogels. Proc. Natl Acad. Sci. USA 104, 12994–12998 (2007).
Fuchs, A. D. & Tiller, J. C. Contact-active antimicrobial coatings derived from aqueous suspensions. Angew. Chem. Int. Ed. 45, 6759–6762 (2006).
Nurdin, N., Helary, G. & Sauvet, G. Biocidal polymers active by contact. 2. Biological evaluation of polyurethane coating with pendant quaternary ammonium-salts. J. Appl. Polym. Sci. 50, 663–670 (1993).
Madkour, A. E., Dabkowski, J. A., Nusslein, K. & Tew, G. N. Fast disinfecting antimicrobial surfaces. Langmuir 25, 1060–1067 (2009).
Jia, Z. S., Shen, D. F. & Xu, W. L. Synthesis and antibacterial activities of quaternary ammonium salt of chitosan. Carbohydr. Res. 333, 1–6 (2001).
Mao, S. R. et al. Synthesis, characterization and cytotoxicity of poly(ethyleneglycol)-graft-trimethyl chitosan block copolymers. Biomaterials 26, 6343–6356 (2005).
Zhu, S. Y., Qian, F., Zhang, Y., Tang, C. & Yin, C. H. Synthesis and characterization of PEG modified N-trimethylaminoethylmethacrylate chitosan nanoparticles. Eur. Polym. J. 43, 2244–2253 (2007).
Theis, T. & Stahl, U. Antifungal proteins: Targets, mechanisms and prospective applications. Cell. Mol. Life Sci. 61, 437–455 (2004).
Peppas, N. A., Hilt, J. Z., Khademhosseini, A. & Langer, R. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Adv. Mater. 18, 1345–1360 (2006).
Li, Q., Wang, D. A. & Elisseeff, J. H. Heterogeneous-phase reaction of glycidyl methacrylate and chondroitin sulfate: Mechanism of ring-opening-transesterification competition. Macromolecules 36, 2556–2562 (2003).
Sadovskaya, I., Brisson, J. R., Lam, J. S., Richards, J. C. & Altman, E. A. Structural elucidation of the lipopolysaccharide core regions of the wild-type strain PAO1 and O-chain-deficient mutant strains AK1401 and AK1012 from Pseudomonas aeruginosa serotype O5. Eur. J. Biochem. 255, 673–684 (1998).
Cheng, G., Xue, H., Zhang, Z., Chen, S. & Jiang, S. A switchable biocompatible polymer surface with self-sterilizing and nonfouling capabilities. Angew. Chem. Int. Ed. 47, 8831–8834 (2008).
Ostuni, E., Chapman, R. G., Holmlin, R. E., Takayama, S. & Whitesides, G. M. A survey of structure–property relationships of surfaces that resist the adsorption of protein. Langmuir 17, 5605–5620 (2001).
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.
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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