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
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
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