Antibiofilm coatings based on protein-engineered polymers and antimicrobial peptides for preventing implant-associated infections

Sergio Acosta; Arturo Ibañez-Fonseca; Conrado Aparicio; J. Carlos Rodríguez-Cabello

doi:10.1039/d0bm00155d

Antibiofilm coatings based on protein-engineered polymers and antimicrobial peptides for preventing implant-associated infections

Sergio Acosta, Arturo Ibañez-Fonseca, Conrado Aparicio, J. Carlos Rodríguez-Cabello

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40 Scopus citations

Abstract

Implant-associated infections (IAIs) are one of the leading concerns in orthopedics and dentistry as they commonly lead to implant failure. The presence of biofilms and, increasingly frequently, drug-resistant bacteria further impairs the efficacy of conventional antibiotics. Immobilization of antimicrobial peptides (AMPs) on implant surfaces is a promising alternative to antibiotics for prevention of IAIs. In addition, the use of functional linkers for the AMP tethering enables to increase the antimicrobial potential and the bioactivities of the coating. In this study, an extracellular-matrix-mimicking system based on elastin-like recombinamers (ELRs) has been developed for the covalent anchoring of AMPs and investigated for use as a hybrid antibiofilm coating. A drip-flow biofilm reactor was used to simulate in vivo environmental dynamic conditions, thus showing that the presence of the AMPs in the hybrid coatings provided strong antibiofilm activity against monospecies and microcosm biofilm models of clinical relevance. These results, together with an excellent cytocompatibility towards primary gingival fibroblasts, encourage the use of ELRs as multivalent platforms for AMPs and open up a wide range of possibilities in the biofabrication of advanced coatings combining the antibiofilm potential of AMPs and the outstanding tunability and biomechanical properties of the ELRs.

Original language	English (US)
Pages (from-to)	2866-2877
Number of pages	12
Journal	Biomaterials science
Volume	8
Issue number	10
DOIs	https://doi.org/10.1039/d0bm00155d
State	Published - May 21 2020

Bibliographical note

Funding Information:
The authors would like to thank Professor Joel Rudney (University of Minnesota) for facilitating the use of microbiology facilities and the S. gordonii bacteria and oral bacterial microcosms used here and Professor Sven Gorr (University of Minnesota) for facilitating the use of his lab facilities. The authors also acknowledge Ms Ruoqiong Chen for technical assistance with the drip-flow biofilm bioreactor and antimicrobial tests. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. CLSM was performed at the University of Minnesota Imaging Centers (http://uic.umn.edu) with the assistance of Dr Guillermo Marques. The authors are grateful for funding from the European Commission (NMP-2014-646075), the Spanish Government (MAT2016-78903-R and PCIN-2015-010 (FunBioPlas)), the Junta de Castilla y León (VA317P18) and the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León.

Publisher Copyright:
© 2020 The Royal Society of Chemistry.

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title = "Antibiofilm coatings based on protein-engineered polymers and antimicrobial peptides for preventing implant-associated infections",

abstract = "Implant-associated infections (IAIs) are one of the leading concerns in orthopedics and dentistry as they commonly lead to implant failure. The presence of biofilms and, increasingly frequently, drug-resistant bacteria further impairs the efficacy of conventional antibiotics. Immobilization of antimicrobial peptides (AMPs) on implant surfaces is a promising alternative to antibiotics for prevention of IAIs. In addition, the use of functional linkers for the AMP tethering enables to increase the antimicrobial potential and the bioactivities of the coating. In this study, an extracellular-matrix-mimicking system based on elastin-like recombinamers (ELRs) has been developed for the covalent anchoring of AMPs and investigated for use as a hybrid antibiofilm coating. A drip-flow biofilm reactor was used to simulate in vivo environmental dynamic conditions, thus showing that the presence of the AMPs in the hybrid coatings provided strong antibiofilm activity against monospecies and microcosm biofilm models of clinical relevance. These results, together with an excellent cytocompatibility towards primary gingival fibroblasts, encourage the use of ELRs as multivalent platforms for AMPs and open up a wide range of possibilities in the biofabrication of advanced coatings combining the antibiofilm potential of AMPs and the outstanding tunability and biomechanical properties of the ELRs.",

author = "Sergio Acosta and Arturo Iba{\~n}ez-Fonseca and Conrado Aparicio and Rodr{\'i}guez-Cabello, {J. Carlos}",

note = "Funding Information: The authors would like to thank Professor Joel Rudney (University of Minnesota) for facilitating the use of microbiology facilities and the S. gordonii bacteria and oral bacterial microcosms used here and Professor Sven Gorr (University of Minnesota) for facilitating the use of his lab facilities. The authors also acknowledge Ms Ruoqiong Chen for technical assistance with the drip-flow biofilm bioreactor and antimicrobial tests. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. CLSM was performed at the University of Minnesota Imaging Centers (http://uic.umn.edu) with the assistance of Dr Guillermo Marques. The authors are grateful for funding from the European Commission (NMP-2014-646075), the Spanish Government (MAT2016-78903-R and PCIN-2015-010 (FunBioPlas)), the Junta de Castilla y Le{\'o}n (VA317P18) and the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y Le{\'o}n. Publisher Copyright: {\textcopyright} 2020 The Royal Society of Chemistry.",

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AU - Rodríguez-Cabello, J. Carlos

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N2 - Implant-associated infections (IAIs) are one of the leading concerns in orthopedics and dentistry as they commonly lead to implant failure. The presence of biofilms and, increasingly frequently, drug-resistant bacteria further impairs the efficacy of conventional antibiotics. Immobilization of antimicrobial peptides (AMPs) on implant surfaces is a promising alternative to antibiotics for prevention of IAIs. In addition, the use of functional linkers for the AMP tethering enables to increase the antimicrobial potential and the bioactivities of the coating. In this study, an extracellular-matrix-mimicking system based on elastin-like recombinamers (ELRs) has been developed for the covalent anchoring of AMPs and investigated for use as a hybrid antibiofilm coating. A drip-flow biofilm reactor was used to simulate in vivo environmental dynamic conditions, thus showing that the presence of the AMPs in the hybrid coatings provided strong antibiofilm activity against monospecies and microcosm biofilm models of clinical relevance. These results, together with an excellent cytocompatibility towards primary gingival fibroblasts, encourage the use of ELRs as multivalent platforms for AMPs and open up a wide range of possibilities in the biofabrication of advanced coatings combining the antibiofilm potential of AMPs and the outstanding tunability and biomechanical properties of the ELRs.

AB - Implant-associated infections (IAIs) are one of the leading concerns in orthopedics and dentistry as they commonly lead to implant failure. The presence of biofilms and, increasingly frequently, drug-resistant bacteria further impairs the efficacy of conventional antibiotics. Immobilization of antimicrobial peptides (AMPs) on implant surfaces is a promising alternative to antibiotics for prevention of IAIs. In addition, the use of functional linkers for the AMP tethering enables to increase the antimicrobial potential and the bioactivities of the coating. In this study, an extracellular-matrix-mimicking system based on elastin-like recombinamers (ELRs) has been developed for the covalent anchoring of AMPs and investigated for use as a hybrid antibiofilm coating. A drip-flow biofilm reactor was used to simulate in vivo environmental dynamic conditions, thus showing that the presence of the AMPs in the hybrid coatings provided strong antibiofilm activity against monospecies and microcosm biofilm models of clinical relevance. These results, together with an excellent cytocompatibility towards primary gingival fibroblasts, encourage the use of ELRs as multivalent platforms for AMPs and open up a wide range of possibilities in the biofabrication of advanced coatings combining the antibiofilm potential of AMPs and the outstanding tunability and biomechanical properties of the ELRs.

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Antibiofilm coatings based on protein-engineered polymers and antimicrobial peptides for preventing implant-associated infections

Abstract

Bibliographical note

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Nikon A1RHD Multiphoton Upright Confocal

Nikon Inverted TI-E Deconvolution Microscope

University Imaging Centers

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Antibiofilm coatings based on protein-engineered polymers and antimicrobial peptides for preventing implant-associated infections

Abstract

Bibliographical note

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Equipment

Nikon A1RHD Multiphoton Upright Confocal

Nikon Inverted TI-E Deconvolution Microscope

University Imaging Centers

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