Hybrid Nanocoatings of Self-assembled Organic-Inorganic Amphiphiles for Prevention of Implant Infections

Zhou Ye; Ting Sang; Kun Li; Nicholas G. Fischer; Isha Mutreja; Constanza Echeverría; Dhiraj Kumar; Zhen Tang; Conrado Aparicio

doi:10.1016/j.actbio.2021.12.008

Hybrid Nanocoatings of Self-assembled Organic-Inorganic Amphiphiles for Prevention of Implant Infections

Zhou Ye, Ting Sang, Kun Li, Nicholas G. Fischer, Isha Mutreja, Constanza Echeverría, Dhiraj Kumar, Zhen Tang, Conrado Aparicio

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

Antimicrobial coatings are one of the most promising strategies to prevent bacterial infections in orthopedic and dental implants. Combining antimicrobial agents with different antimicrobial mechanisms might have synergistic effects and be more potent. Others have shown that nanocomposites of silver nanoparticles (AgNPs) decorated with antimicrobial peptides (AMPs) show increased potency as free agents in solution. However, similar nanocomposites have not been explored to coat biomaterials through cooperative weak electrostatic attraction forces between AMP, AgNPs and substrates in need of protection against infection. In this work, we synthesized self-assembled antimicrobial amphiphiles of an AMP, GL13K. Then, we decorated the AMP nanostructures with AgNPs, which were finally used to coat etched Ti (eTi) surfaces. The strong hydrogen bonding between the AMP amphiphiles and the polar eTi yielded a robust and stable coating. When compared to single AgNP or single AMP coatings, our hybrid nanocoatings had notably higher in vitro antimicrobial potency against multiple bacteria strains related to implant infection. The hybrid coating also showed relevant antimicrobial activity in an in vivo subcutaneous infection model in rats. This work advances the application of AgNP/AMP nanocomposites as effective coatings for prevention of implant infections. Statement of significance: High morbidity, mortality and elevated costs are associated with orthopedic and dental implant infections. Conventional antibiotic treatment is ineffective due to barrier-like extracellular polymeric substances in biofilms and the increasing threat from antibiotic resistance. Antimicrobial coatings are one of the most promising strategies, but the performance is usually unsatisfactory, especially when tested in vivo. Here, we present a hybrid nanocoating with different modes of action to prevent implant infections using self-assembled antimicrobial peptide (AMP) amphiphiles decorated with silver nanoparticles (AgNPs). When compared to single AgNP or AMP coatings, our hybrid nanocoatings showed significant increases in antimicrobial potency against multiple implant infection-related bacterial strains in vitro and in an in vivo rat subcutaneous infection model.

Original language	English (US)
Journal	Acta Biomaterialia
DOIs	https://doi.org/10.1016/j.actbio.2021.12.008
State	Published - Dec 2021

Bibliographical note

Funding Information:
This research was supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health [grant number R01DE026117 to C. A., T90DE0227232 to N.G.F.], the National Institutes of Health's National Center for Advancing Translational Sciences [Translational Research Development Program- TRDP award to Z.Y. from grant UL1TR002494], the National Natural Science Foundation of China [grant number 82160190 to T.S.], the Jiangxi Provincial Department of Science and Technology, China [grant number 20203BBGL73156 to T.S., 20192BBG70022 to T.S.], and 3 M Gives [Key Opinion Leaders Scholarship to C.E]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the Narional Science Foundation through the National Coordinated (NNCI) under Award Number ECCS-2025124. Confocal laser scanning microscopy was performed at the University of Minnesota – University Imaging Center (SCR_020997).

Funding Information:
This research was supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health [grant number R01DE026117 to C. A. T90DE0227232 to N.G.F.], the National Institutes of Health's National Center for Advancing Translational Sciences [Translational Research Development Program- TRDP award to Z.Y. from grant UL1TR002494], the National Natural Science Foundation of China [grant number 82160190 to T.S.], the Jiangxi Provincial Department of Science and Technology, China [grant number 20203BBGL73156 to T.S. 20192BBG70022 to T.S.], and 3 M Gives [Key Opinion Leaders Scholarship to C.E]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the Narional Science Foundation through the National Coordinated (NNCI) under Award Number ECCS-2025124. Confocal laser scanning microscopy was performed at the University of Minnesota ? University Imaging Center (SCR_020997).

Publisher Copyright:
© 2021 Acta Materialia Inc.

Keywords

Antimicrobial coatings
Antimicrobial peptides
Hybrid nanostructures
Peri-implant infections
Silver nanoparticle

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1016/j.actbio.2021.12.008

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@article{d8ce2b0390be445889df86dadbb12751,

title = "Hybrid Nanocoatings of Self-assembled Organic-Inorganic Amphiphiles for Prevention of Implant Infections",

abstract = "Antimicrobial coatings are one of the most promising strategies to prevent bacterial infections in orthopedic and dental implants. Combining antimicrobial agents with different antimicrobial mechanisms might have synergistic effects and be more potent. Others have shown that nanocomposites of silver nanoparticles (AgNPs) decorated with antimicrobial peptides (AMPs) show increased potency as free agents in solution. However, similar nanocomposites have not been explored to coat biomaterials through cooperative weak electrostatic attraction forces between AMP, AgNPs and substrates in need of protection against infection. In this work, we synthesized self-assembled antimicrobial amphiphiles of an AMP, GL13K. Then, we decorated the AMP nanostructures with AgNPs, which were finally used to coat etched Ti (eTi) surfaces. The strong hydrogen bonding between the AMP amphiphiles and the polar eTi yielded a robust and stable coating. When compared to single AgNP or single AMP coatings, our hybrid nanocoatings had notably higher in vitro antimicrobial potency against multiple bacteria strains related to implant infection. The hybrid coating also showed relevant antimicrobial activity in an in vivo subcutaneous infection model in rats. This work advances the application of AgNP/AMP nanocomposites as effective coatings for prevention of implant infections. Statement of significance: High morbidity, mortality and elevated costs are associated with orthopedic and dental implant infections. Conventional antibiotic treatment is ineffective due to barrier-like extracellular polymeric substances in biofilms and the increasing threat from antibiotic resistance. Antimicrobial coatings are one of the most promising strategies, but the performance is usually unsatisfactory, especially when tested in vivo. Here, we present a hybrid nanocoating with different modes of action to prevent implant infections using self-assembled antimicrobial peptide (AMP) amphiphiles decorated with silver nanoparticles (AgNPs). When compared to single AgNP or AMP coatings, our hybrid nanocoatings showed significant increases in antimicrobial potency against multiple implant infection-related bacterial strains in vitro and in an in vivo rat subcutaneous infection model.",

keywords = "Antimicrobial coatings, Antimicrobial peptides, Hybrid nanostructures, Peri-implant infections, Silver nanoparticle",

author = "Zhou Ye and Ting Sang and Kun Li and Fischer, {Nicholas G.} and Isha Mutreja and Constanza Echeverr{\'i}a and Dhiraj Kumar and Zhen Tang and Conrado Aparicio",

note = "Funding Information: This research was supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health [grant number R01DE026117 to C. A., T90DE0227232 to N.G.F.], the National Institutes of Health's National Center for Advancing Translational Sciences [Translational Research Development Program- TRDP award to Z.Y. from grant UL1TR002494], the National Natural Science Foundation of China [grant number 82160190 to T.S.], the Jiangxi Provincial Department of Science and Technology, China [grant number 20203BBGL73156 to T.S., 20192BBG70022 to T.S.], and 3 M Gives [Key Opinion Leaders Scholarship to C.E]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the Narional Science Foundation through the National Coordinated (NNCI) under Award Number ECCS-2025124. Confocal laser scanning microscopy was performed at the University of Minnesota – University Imaging Center (SCR_020997). Funding Information: This research was supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health [grant number R01DE026117 to C. A. T90DE0227232 to N.G.F.], the National Institutes of Health's National Center for Advancing Translational Sciences [Translational Research Development Program- TRDP award to Z.Y. from grant UL1TR002494], the National Natural Science Foundation of China [grant number 82160190 to T.S.], the Jiangxi Provincial Department of Science and Technology, China [grant number 20203BBGL73156 to T.S. 20192BBG70022 to T.S.], and 3 M Gives [Key Opinion Leaders Scholarship to C.E]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the Narional Science Foundation through the National Coordinated (NNCI) under Award Number ECCS-2025124. Confocal laser scanning microscopy was performed at the University of Minnesota ? University Imaging Center (SCR_020997). Publisher Copyright: {\textcopyright} 2021 Acta Materialia Inc.",

year = "2021",

month = dec,

doi = "10.1016/j.actbio.2021.12.008",

language = "English (US)",

journal = "Acta Biomaterialia",

issn = "1742-7061",

publisher = "Acta Materialia Inc",

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TY - JOUR

T1 - Hybrid Nanocoatings of Self-assembled Organic-Inorganic Amphiphiles for Prevention of Implant Infections

AU - Ye, Zhou

AU - Sang, Ting

AU - Li, Kun

AU - Fischer, Nicholas G.

AU - Mutreja, Isha

AU - Echeverría, Constanza

AU - Kumar, Dhiraj

AU - Tang, Zhen

AU - Aparicio, Conrado

N1 - Funding Information: This research was supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health [grant number R01DE026117 to C. A., T90DE0227232 to N.G.F.], the National Institutes of Health's National Center for Advancing Translational Sciences [Translational Research Development Program- TRDP award to Z.Y. from grant UL1TR002494], the National Natural Science Foundation of China [grant number 82160190 to T.S.], the Jiangxi Provincial Department of Science and Technology, China [grant number 20203BBGL73156 to T.S., 20192BBG70022 to T.S.], and 3 M Gives [Key Opinion Leaders Scholarship to C.E]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the Narional Science Foundation through the National Coordinated (NNCI) under Award Number ECCS-2025124. Confocal laser scanning microscopy was performed at the University of Minnesota – University Imaging Center (SCR_020997). Funding Information: This research was supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health [grant number R01DE026117 to C. A. T90DE0227232 to N.G.F.], the National Institutes of Health's National Center for Advancing Translational Sciences [Translational Research Development Program- TRDP award to Z.Y. from grant UL1TR002494], the National Natural Science Foundation of China [grant number 82160190 to T.S.], the Jiangxi Provincial Department of Science and Technology, China [grant number 20203BBGL73156 to T.S. 20192BBG70022 to T.S.], and 3 M Gives [Key Opinion Leaders Scholarship to C.E]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Parts of this work were carried out in the University of Minnesota I.T. Characterization Facility, which receives partial support from NSF through the MRSEC program. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the Narional Science Foundation through the National Coordinated (NNCI) under Award Number ECCS-2025124. Confocal laser scanning microscopy was performed at the University of Minnesota ? University Imaging Center (SCR_020997). Publisher Copyright: © 2021 Acta Materialia Inc.

PY - 2021/12

Y1 - 2021/12

N2 - Antimicrobial coatings are one of the most promising strategies to prevent bacterial infections in orthopedic and dental implants. Combining antimicrobial agents with different antimicrobial mechanisms might have synergistic effects and be more potent. Others have shown that nanocomposites of silver nanoparticles (AgNPs) decorated with antimicrobial peptides (AMPs) show increased potency as free agents in solution. However, similar nanocomposites have not been explored to coat biomaterials through cooperative weak electrostatic attraction forces between AMP, AgNPs and substrates in need of protection against infection. In this work, we synthesized self-assembled antimicrobial amphiphiles of an AMP, GL13K. Then, we decorated the AMP nanostructures with AgNPs, which were finally used to coat etched Ti (eTi) surfaces. The strong hydrogen bonding between the AMP amphiphiles and the polar eTi yielded a robust and stable coating. When compared to single AgNP or single AMP coatings, our hybrid nanocoatings had notably higher in vitro antimicrobial potency against multiple bacteria strains related to implant infection. The hybrid coating also showed relevant antimicrobial activity in an in vivo subcutaneous infection model in rats. This work advances the application of AgNP/AMP nanocomposites as effective coatings for prevention of implant infections. Statement of significance: High morbidity, mortality and elevated costs are associated with orthopedic and dental implant infections. Conventional antibiotic treatment is ineffective due to barrier-like extracellular polymeric substances in biofilms and the increasing threat from antibiotic resistance. Antimicrobial coatings are one of the most promising strategies, but the performance is usually unsatisfactory, especially when tested in vivo. Here, we present a hybrid nanocoating with different modes of action to prevent implant infections using self-assembled antimicrobial peptide (AMP) amphiphiles decorated with silver nanoparticles (AgNPs). When compared to single AgNP or AMP coatings, our hybrid nanocoatings showed significant increases in antimicrobial potency against multiple implant infection-related bacterial strains in vitro and in an in vivo rat subcutaneous infection model.

AB - Antimicrobial coatings are one of the most promising strategies to prevent bacterial infections in orthopedic and dental implants. Combining antimicrobial agents with different antimicrobial mechanisms might have synergistic effects and be more potent. Others have shown that nanocomposites of silver nanoparticles (AgNPs) decorated with antimicrobial peptides (AMPs) show increased potency as free agents in solution. However, similar nanocomposites have not been explored to coat biomaterials through cooperative weak electrostatic attraction forces between AMP, AgNPs and substrates in need of protection against infection. In this work, we synthesized self-assembled antimicrobial amphiphiles of an AMP, GL13K. Then, we decorated the AMP nanostructures with AgNPs, which were finally used to coat etched Ti (eTi) surfaces. The strong hydrogen bonding between the AMP amphiphiles and the polar eTi yielded a robust and stable coating. When compared to single AgNP or single AMP coatings, our hybrid nanocoatings had notably higher in vitro antimicrobial potency against multiple bacteria strains related to implant infection. The hybrid coating also showed relevant antimicrobial activity in an in vivo subcutaneous infection model in rats. This work advances the application of AgNP/AMP nanocomposites as effective coatings for prevention of implant infections. Statement of significance: High morbidity, mortality and elevated costs are associated with orthopedic and dental implant infections. Conventional antibiotic treatment is ineffective due to barrier-like extracellular polymeric substances in biofilms and the increasing threat from antibiotic resistance. Antimicrobial coatings are one of the most promising strategies, but the performance is usually unsatisfactory, especially when tested in vivo. Here, we present a hybrid nanocoating with different modes of action to prevent implant infections using self-assembled antimicrobial peptide (AMP) amphiphiles decorated with silver nanoparticles (AgNPs). When compared to single AgNP or AMP coatings, our hybrid nanocoatings showed significant increases in antimicrobial potency against multiple implant infection-related bacterial strains in vitro and in an in vivo rat subcutaneous infection model.

KW - Antimicrobial coatings

KW - Antimicrobial peptides

KW - Hybrid nanostructures

KW - Peri-implant infections

KW - Silver nanoparticle

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ER -

Hybrid Nanocoatings of Self-assembled Organic-Inorganic Amphiphiles for Prevention of Implant Infections

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Hybrid Nanocoatings of Self-assembled Organic-Inorganic Amphiphiles for Prevention of Implant Infections

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