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An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility

Orthopedic device-related infections remain a serious challenge to treat. Central to these infections are bacterial biofilms that form on the orthopedic implant itself. These biofilms shield the bacteria from the host immune system and most common antibiotic drugs, which renders them essentially ant...

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Autores principales: Coppola, Guglielmo Attilio, Onsea, Jolien, Moriarty, T. Fintan, Nehrbass, Dirk, Constant, Caroline, Zeiter, Stephan, Aktan, Merve Kübra, Braem, Annabel, Van der Eycken, Erik V., Steenackers, Hans P., Metsemakers, Willem-Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097006/
https://www.ncbi.nlm.nih.gov/pubmed/33967997
http://dx.doi.org/10.3389/fmicb.2021.658521
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author Coppola, Guglielmo Attilio
Onsea, Jolien
Moriarty, T. Fintan
Nehrbass, Dirk
Constant, Caroline
Zeiter, Stephan
Aktan, Merve Kübra
Braem, Annabel
Van der Eycken, Erik V.
Steenackers, Hans P.
Metsemakers, Willem-Jan
author_facet Coppola, Guglielmo Attilio
Onsea, Jolien
Moriarty, T. Fintan
Nehrbass, Dirk
Constant, Caroline
Zeiter, Stephan
Aktan, Merve Kübra
Braem, Annabel
Van der Eycken, Erik V.
Steenackers, Hans P.
Metsemakers, Willem-Jan
author_sort Coppola, Guglielmo Attilio
collection PubMed
description Orthopedic device-related infections remain a serious challenge to treat. Central to these infections are bacterial biofilms that form on the orthopedic implant itself. These biofilms shield the bacteria from the host immune system and most common antibiotic drugs, which renders them essentially antibiotic-tolerant. There is an urgent clinical need for novel strategies to prevent these serious infections that do not involve conventional antibiotics. Recently, a novel antibiofilm coating for titanium surfaces was developed based on 5-(4-bromophenyl)-N-cyclopentyl-1-octyl-1H-imidazol-2-amine as an active biofilm inhibitor. In the current study we present an optimized coating protocol that allowed for a 5-fold higher load of this active compound, whilst shortening the manufacturing process. When applied to titanium disks, the newly optimized coating was resilient to the most common sterilization procedures and it induced a 1 log reduction in biofilm cells of a clinical Staphylococcus aureus isolate (JAR060131) in vitro, without affecting the planktonic phase. Moreover, the antibiofilm effect of the coating in combination with the antibiotic cefuroxime was higher than cefuroxime treatment alone. Furthermore, the coating was successfully applied to a human-scale fracture fixation device resulting in a loading that was comparable to the titanium disk model. Finally, an in vivo biocompatibility and healing study in a rabbit osteotomy model indicated that these coated implants did not negatively affect fracture healing or osteointegration. These findings put our technology one step closer to clinical trials, confirming its potential in fighting orthopedic infections without compromising healing.
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spelling pubmed-80970062021-05-06 An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility Coppola, Guglielmo Attilio Onsea, Jolien Moriarty, T. Fintan Nehrbass, Dirk Constant, Caroline Zeiter, Stephan Aktan, Merve Kübra Braem, Annabel Van der Eycken, Erik V. Steenackers, Hans P. Metsemakers, Willem-Jan Front Microbiol Microbiology Orthopedic device-related infections remain a serious challenge to treat. Central to these infections are bacterial biofilms that form on the orthopedic implant itself. These biofilms shield the bacteria from the host immune system and most common antibiotic drugs, which renders them essentially antibiotic-tolerant. There is an urgent clinical need for novel strategies to prevent these serious infections that do not involve conventional antibiotics. Recently, a novel antibiofilm coating for titanium surfaces was developed based on 5-(4-bromophenyl)-N-cyclopentyl-1-octyl-1H-imidazol-2-amine as an active biofilm inhibitor. In the current study we present an optimized coating protocol that allowed for a 5-fold higher load of this active compound, whilst shortening the manufacturing process. When applied to titanium disks, the newly optimized coating was resilient to the most common sterilization procedures and it induced a 1 log reduction in biofilm cells of a clinical Staphylococcus aureus isolate (JAR060131) in vitro, without affecting the planktonic phase. Moreover, the antibiofilm effect of the coating in combination with the antibiotic cefuroxime was higher than cefuroxime treatment alone. Furthermore, the coating was successfully applied to a human-scale fracture fixation device resulting in a loading that was comparable to the titanium disk model. Finally, an in vivo biocompatibility and healing study in a rabbit osteotomy model indicated that these coated implants did not negatively affect fracture healing or osteointegration. These findings put our technology one step closer to clinical trials, confirming its potential in fighting orthopedic infections without compromising healing. Frontiers Media S.A. 2021-04-21 /pmc/articles/PMC8097006/ /pubmed/33967997 http://dx.doi.org/10.3389/fmicb.2021.658521 Text en Copyright © 2021 Coppola, Onsea, Moriarty, Nehrbass, Constant, Zeiter, Aktan, Braem, Van der Eycken, Steenackers and Metsemakers. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Coppola, Guglielmo Attilio
Onsea, Jolien
Moriarty, T. Fintan
Nehrbass, Dirk
Constant, Caroline
Zeiter, Stephan
Aktan, Merve Kübra
Braem, Annabel
Van der Eycken, Erik V.
Steenackers, Hans P.
Metsemakers, Willem-Jan
An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility
title An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility
title_full An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility
title_fullStr An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility
title_full_unstemmed An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility
title_short An Improved 2-Aminoimidazole Based Anti-Biofilm Coating for Orthopedic Implants: Activity, Stability, and in vivo Biocompatibility
title_sort improved 2-aminoimidazole based anti-biofilm coating for orthopedic implants: activity, stability, and in vivo biocompatibility
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097006/
https://www.ncbi.nlm.nih.gov/pubmed/33967997
http://dx.doi.org/10.3389/fmicb.2021.658521
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