Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/154112
Title: | Precisely structured nitric-oxide-releasing copolymer brush defeats broad-spectrum catheter-associated biofilm infections in vivo | Authors: | Hou, Zheng Wu, Yang Xu, Chen Reghu, Sheethal Shang, Zifang Chen, Jingjie Pranantyo, Dicky Marimuth, Kalisvar De, Partha Pratim Ng, Oon Tek Pethe, Kevin Kang, En-Tang Li, Peng Chan-Park, Mary B. |
Keywords: | Engineering::Chemical engineering::Polymers and polymer manufacture | Issue Date: | 2020 | Source: | Hou, Z., Wu, Y., Xu, C., Reghu, S., Shang, Z., Chen, J., Pranantyo, D., Marimuth, K., De, P. P., Ng, O. T., Pethe, K., Kang, E., Li, P. & Chan-Park, M. B. (2020). Precisely structured nitric-oxide-releasing copolymer brush defeats broad-spectrum catheter-associated biofilm infections in vivo. ACS Central Science, 6(11), 2031-2045. https://dx.doi.org/10.1021/acscentsci.0c00755 | Journal: | ACS Central Science | Abstract: | Gram-negative bacteria cannot be easily eradicated by antibiotics and are a major source of recalcitrant infections of indwelling medical devices. Among various device-associated infections, intravascular catheter infection is a leading cause of mortality. Prior approaches to surface modification, such as antibiotics impregnation, hydrophilization, unstructured NO-releasing, etc., have failed to achieve adequate infection-resistant coatings. We report a precision-structured diblock copolymer brush (H(N)-b-S) composed of a surface antifouling block of poly(sulfobetaine methacrylate) (S) and a subsurface bactericidal block (H(N)) of nitric-oxide-emitting functionalized poly(hydroxyethyl methacrylate) (H) covalently grafted from the inner and outer surfaces of a polyurethane catheter. The block copolymer architecture of the coating is important for achieving good broad-spectrum anti-biofilm activity with good biocompatibility and low fouling. The coating procedure is scalable to clinically useful catheter lengths. Only the block copolymer brush coating ((H(N)-b-S)) shows unprecedented, above 99.99%, in vitro biofilm inhibition of Gram-positive and Gram-negative bacteria, 100-fold better than previous coatings. It has negligible toxicity toward mammalian cells and excellent blood compatibility. In a murine subcutaneous infection model, it achieves >99.99% biofilm reduction of Gram-positive and Gram-negative bacteria compared with <90% for silver catheter, while in a porcine central venous catheter infection model, it achieves >99.99% reduction of MRSA with 5-day implantation. This precision coating is readily applicable for long-term biofilm-resistant and blood-compatible copolymer coatings covalently grafted from a wide range of medical devices. | URI: | https://hdl.handle.net/10356/154112 | ISSN: | 2374-7951 | DOI: | 10.1021/acscentsci.0c00755 | Schools: | School of Chemical and Biomedical Engineering Lee Kong Chian School of Medicine (LKCMedicine) School of Physical and Mathematical Sciences |
Research Centres: | Centre for Antimicrobial Bioengineering | Rights: | © 2020 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles SCBE Journal Articles SPMS Journal Articles |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Precisely Structured Nitric-Oxide-Releasing Copolymer Brush Defeats Broad-Spectrum Catheter-Associated Biofilm Infections In Vivo.pdf | 5.16 MB | Adobe PDF | View/Open | |
Precisely Structured Coating revised Supporting submitted tracked.pdf | 2.22 MB | Adobe PDF | View/Open |
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