4.8 Article

Mixed-charge pseudo-zwitterionic copolymer brush as broad spectrum antibiofilm coating

Journal

BIOMATERIALS
Volume 273, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120794

Keywords

Pseudo-zwitterionic copolymer; Mixed-charge; Broad spectrum antibiofilm; Polymerization kinetics; Catheter coating

Funding

  1. Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 3 grants [MOE2013-T3-1-004, MOE2018-T3-1-003]
  2. Singapore Ministry of Health Industry Alignment Fund [NMRC/MOHIAFCAT2/003/2014]
  3. A*STAR Industry Alignment Fund [H17/01/a0/0M9]
  4. A*STAR RIE2020 Advanced Manufacturing and Engineering (AME) IAP-PP Specialty Chemicals Program [A1786a0032]
  5. Nanyang Technological University (NTU)
  6. NTU Ph.D. scholarships

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This study demonstrates the effectiveness of a novel mixed-charge copolymer brush coating in combating biofilm formation, outperforming traditional zwitterionic polymers. By utilizing oppositely charged monomers, a greater than 99% reduction in biofilm formation was achieved against various bacteria in vitro, with excellent long-term efficacy in murine infection models. These findings suggest the potential of combining readily available singly charged monomers for potent antibiofilm applications.
Zwitterionic polymers are classical antifouling polymers but they require specialized monomers that have cationic and anionic charges integrated into a single monomer. Herein, we show that pseudo-zwitterionic copolymers synthesized from a mixture of 2 monomers each having a single opposite polarity has excellent antibiofilm efficacy. We have discovered a new mixed-charge copolymer brush (#1-A) synthesized from 2 oppositely charged monomers, the anionic SPM (3-Sulfopropyl methacrylate) and the cationic AMPTMA ((3-Acrylamidopropyl) trimethylammonium chloride), that achieves broad spectrum in vitro antibiofilm effect of greater than 99% reductions against all six Gram-positive and Gram-negative bacteria tested. In the murine subcutaneous wound catheter infection models, the #1-A has good long-term anti-biofilm efficacy against MRSA and Pseudomonas aeruginosa of 3.41 and 3.19 orders respectively, outperforming previous mixed-charge copolymer coatings. We discovered a new method to choose the cationic/anionic pair combination to form the best antibiofilm copolymer brush coating by exploiting the solution polymerization kinetics disparity between the cationic and anionic monomers. We also showed that #1-A is softer and has higher hydration than the classical zwitterionic polymer. This study shows the possibility of achieving potent antibiofilm efficacy by combining readily available opposite singly charged monomers.

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