Development of an Antimicrobial Peptide SAAP-148-Functionalized Supramolecular Coating on Titanium to Prevent Biomaterial-Associated Infections

Moniek G.J. Schmitz; Martijn Riool; Leonie de Boer; Annika F. Vrehen; Paul A.A. Bartels; Sebastian A.J. Zaat; Patricia Y.W. Dankers

doi:10.1002/admt.202201846

Development of an Antimicrobial Peptide SAAP-148-Functionalized Supramolecular Coating on Titanium to Prevent Biomaterial-Associated Infections

Moniek G.J. Schmitz
, Martijn Riool
, Leonie de Boer
, Annika F. Vrehen
, Paul A.A. Bartels
, Sebastian A.J. Zaat (Corresponding author)
, Patricia Y.W. Dankers (Corresponding author)

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

21 Citations (Scopus)

140 Downloads (Pure)

Abstract

Titanium implants are widely used in medicine but have a risk of biomaterial-associated infection (BAI), of which traditional antibiotic-based treatment is affected by resistance. Antimicrobial peptides (AMPs) are used to successfully kill antibiotic-resistant bacteria. Herein, a supramolecular coating for titanium implants is developed which presents the synthetic antimicrobial and antibiofilm peptide SAAP-148 via supramolecular interactions using ureido-pyrimidinone supramolecular units (UPy-SAAP-148GG). Material characterization of dropcast coatings shows the presence of UPy-SAAP-148GG at the surface. The supramolecular immobilized peptide remains antimicrobially active in dropcast polymer films and can successfully kill (antibiotic-resistant) Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli. Minor toxicity for human dermal fibroblasts is observed, with a reduced cell attachment after 24 h. Subsequently, a dipcoat coating on titanium implants is developed and tested in vivo in a subcutaneous implant infection mouse model with S. aureus administered locally on the implant before implantation to mimic contamination during surgery. The supramolecular coating containing 5 mol% of UPy-SAAP-148GG significantly prevents colonization of the implant surface as well as of the surrounding tissue, with no signs of toxicity. This shows that supramolecular AMP coatings on titanium are eminently suitable to prevent BAI.

Original language	English
Article number	2201846
Journal	Advanced Materials Technologies
Volume	8
Issue number	13
DOIs	https://doi.org/10.1002/admt.202201846
Publication status	Published - 10 Jul 2023

Bibliographical note

Funding Information:
M.G.J.S. and M.R., and S.A.J.Z. and P.Y.W.D. contributed equally to this work. The authors thank Ardine de Vos and Karen Schröder‐Bonneveld (Animal Research Institute AMC (ARIA), Amsterdam UMC) and Clara Guarch‐Pérez (Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC) for their excellent support in the animal experiments. Dr. Jan‐Wouter Drijfhout (Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Centre) is acknowledged for his advice on the peptide synthesis and providing SAAP‐148. This research was financially supported by the DPI, project no. 731.015.505, the Ministry of Education, Culture and Science (Gravity Programs 024.001.035 and 024.003.013), and the research program of Chemelot InSciTe, project EyeSciTe.

Funding Information:
M.G.J.S. and M.R., and S.A.J.Z. and P.Y.W.D. contributed equally to this work. The authors thank Ardine de Vos and Karen Schröder-Bonneveld (Animal Research Institute AMC (ARIA), Amsterdam UMC) and Clara Guarch-Pérez (Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC) for their excellent support in the animal experiments. Dr. Jan-Wouter Drijfhout (Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Centre) is acknowledged for his advice on the peptide synthesis and providing SAAP-148. This research was financially supported by the DPI, project no. 731.015.505, the Ministry of Education, Culture and Science (Gravity Programs 024.001.035 and 024.003.013), and the research program of Chemelot InSciTe, project EyeSciTe.

Publisher Copyright:
© 2023 The Authors. Advanced Materials Technologies published by Wiley-VCH GmbH.

Funding

M.G.J.S. and M.R., and S.A.J.Z. and P.Y.W.D. contributed equally to this work. The authors thank Ardine de Vos and Karen Schröder‐Bonneveld (Animal Research Institute AMC (ARIA), Amsterdam UMC) and Clara Guarch‐Pérez (Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC) for their excellent support in the animal experiments. Dr. Jan‐Wouter Drijfhout (Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Centre) is acknowledged for his advice on the peptide synthesis and providing SAAP‐148. This research was financially supported by the DPI, project no. 731.015.505, the Ministry of Education, Culture and Science (Gravity Programs 024.001.035 and 024.003.013), and the research program of Chemelot InSciTe, project EyeSciTe. M.G.J.S. and M.R., and S.A.J.Z. and P.Y.W.D. contributed equally to this work. The authors thank Ardine de Vos and Karen Schröder-Bonneveld (Animal Research Institute AMC (ARIA), Amsterdam UMC) and Clara Guarch-Pérez (Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC) for their excellent support in the animal experiments. Dr. Jan-Wouter Drijfhout (Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Centre) is acknowledged for his advice on the peptide synthesis and providing SAAP-148. This research was financially supported by the DPI, project no. 731.015.505, the Ministry of Education, Culture and Science (Gravity Programs 024.001.035 and 024.003.013), and the research program of Chemelot InSciTe, project EyeSciTe.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

antimicrobial peptides
biomaterial-associated infections
coatings
SAAP-148
supramolecular biomaterials
titanium
ureido-pyrimidinone

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10.1002/admt.202201846

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title = "Development of an Antimicrobial Peptide SAAP-148-Functionalized Supramolecular Coating on Titanium to Prevent Biomaterial-Associated Infections",

abstract = "Titanium implants are widely used in medicine but have a risk of biomaterial-associated infection (BAI), of which traditional antibiotic-based treatment is affected by resistance. Antimicrobial peptides (AMPs) are used to successfully kill antibiotic-resistant bacteria. Herein, a supramolecular coating for titanium implants is developed which presents the synthetic antimicrobial and antibiofilm peptide SAAP-148 via supramolecular interactions using ureido-pyrimidinone supramolecular units (UPy-SAAP-148GG). Material characterization of dropcast coatings shows the presence of UPy-SAAP-148GG at the surface. The supramolecular immobilized peptide remains antimicrobially active in dropcast polymer films and can successfully kill (antibiotic-resistant) Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli. Minor toxicity for human dermal fibroblasts is observed, with a reduced cell attachment after 24 h. Subsequently, a dipcoat coating on titanium implants is developed and tested in vivo in a subcutaneous implant infection mouse model with S. aureus administered locally on the implant before implantation to mimic contamination during surgery. The supramolecular coating containing 5 mol\% of UPy-SAAP-148GG significantly prevents colonization of the implant surface as well as of the surrounding tissue, with no signs of toxicity. This shows that supramolecular AMP coatings on titanium are eminently suitable to prevent BAI.",

keywords = "antimicrobial peptides, biomaterial-associated infections, coatings, SAAP-148, supramolecular biomaterials, titanium, ureido-pyrimidinone",

author = "Schmitz, \{Moniek G.J.\} and Martijn Riool and \{de Boer\}, Leonie and Vrehen, \{Annika F.\} and Bartels, \{Paul A.A.\} and Zaat, \{Sebastian A.J.\} and Dankers, \{Patricia Y.W.\}",

note = "Funding Information: M.G.J.S. and M.R., and S.A.J.Z. and P.Y.W.D. contributed equally to this work. The authors thank Ardine de Vos and Karen Schr{\"o}der‐Bonneveld (Animal Research Institute AMC (ARIA), Amsterdam UMC) and Clara Guarch‐P{\'e}rez (Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC) for their excellent support in the animal experiments. Dr. Jan‐Wouter Drijfhout (Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Centre) is acknowledged for his advice on the peptide synthesis and providing SAAP‐148. This research was financially supported by the DPI, project no. 731.015.505, the Ministry of Education, Culture and Science (Gravity Programs 024.001.035 and 024.003.013), and the research program of Chemelot InSciTe, project EyeSciTe. Funding Information: M.G.J.S. and M.R., and S.A.J.Z. and P.Y.W.D. contributed equally to this work. The authors thank Ardine de Vos and Karen Schr{\"o}der-Bonneveld (Animal Research Institute AMC (ARIA), Amsterdam UMC) and Clara Guarch-P{\'e}rez (Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC) for their excellent support in the animal experiments. Dr. Jan-Wouter Drijfhout (Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Centre) is acknowledged for his advice on the peptide synthesis and providing SAAP-148. This research was financially supported by the DPI, project no. 731.015.505, the Ministry of Education, Culture and Science (Gravity Programs 024.001.035 and 024.003.013), and the research program of Chemelot InSciTe, project EyeSciTe. Publisher Copyright: {\textcopyright} 2023 The Authors. Advanced Materials Technologies published by Wiley-VCH GmbH.",

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doi = "10.1002/admt.202201846",

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AU - Schmitz, Moniek G.J.

AU - Riool, Martijn

AU - de Boer, Leonie

AU - Vrehen, Annika F.

AU - Bartels, Paul A.A.

AU - Zaat, Sebastian A.J.

AU - Dankers, Patricia Y.W.

N1 - Funding Information: M.G.J.S. and M.R., and S.A.J.Z. and P.Y.W.D. contributed equally to this work. The authors thank Ardine de Vos and Karen Schröder‐Bonneveld (Animal Research Institute AMC (ARIA), Amsterdam UMC) and Clara Guarch‐Pérez (Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC) for their excellent support in the animal experiments. Dr. Jan‐Wouter Drijfhout (Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Centre) is acknowledged for his advice on the peptide synthesis and providing SAAP‐148. This research was financially supported by the DPI, project no. 731.015.505, the Ministry of Education, Culture and Science (Gravity Programs 024.001.035 and 024.003.013), and the research program of Chemelot InSciTe, project EyeSciTe. Funding Information: M.G.J.S. and M.R., and S.A.J.Z. and P.Y.W.D. contributed equally to this work. The authors thank Ardine de Vos and Karen Schröder-Bonneveld (Animal Research Institute AMC (ARIA), Amsterdam UMC) and Clara Guarch-Pérez (Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC) for their excellent support in the animal experiments. Dr. Jan-Wouter Drijfhout (Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Centre) is acknowledged for his advice on the peptide synthesis and providing SAAP-148. This research was financially supported by the DPI, project no. 731.015.505, the Ministry of Education, Culture and Science (Gravity Programs 024.001.035 and 024.003.013), and the research program of Chemelot InSciTe, project EyeSciTe. Publisher Copyright: © 2023 The Authors. Advanced Materials Technologies published by Wiley-VCH GmbH.

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N2 - Titanium implants are widely used in medicine but have a risk of biomaterial-associated infection (BAI), of which traditional antibiotic-based treatment is affected by resistance. Antimicrobial peptides (AMPs) are used to successfully kill antibiotic-resistant bacteria. Herein, a supramolecular coating for titanium implants is developed which presents the synthetic antimicrobial and antibiofilm peptide SAAP-148 via supramolecular interactions using ureido-pyrimidinone supramolecular units (UPy-SAAP-148GG). Material characterization of dropcast coatings shows the presence of UPy-SAAP-148GG at the surface. The supramolecular immobilized peptide remains antimicrobially active in dropcast polymer films and can successfully kill (antibiotic-resistant) Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli. Minor toxicity for human dermal fibroblasts is observed, with a reduced cell attachment after 24 h. Subsequently, a dipcoat coating on titanium implants is developed and tested in vivo in a subcutaneous implant infection mouse model with S. aureus administered locally on the implant before implantation to mimic contamination during surgery. The supramolecular coating containing 5 mol% of UPy-SAAP-148GG significantly prevents colonization of the implant surface as well as of the surrounding tissue, with no signs of toxicity. This shows that supramolecular AMP coatings on titanium are eminently suitable to prevent BAI.

AB - Titanium implants are widely used in medicine but have a risk of biomaterial-associated infection (BAI), of which traditional antibiotic-based treatment is affected by resistance. Antimicrobial peptides (AMPs) are used to successfully kill antibiotic-resistant bacteria. Herein, a supramolecular coating for titanium implants is developed which presents the synthetic antimicrobial and antibiofilm peptide SAAP-148 via supramolecular interactions using ureido-pyrimidinone supramolecular units (UPy-SAAP-148GG). Material characterization of dropcast coatings shows the presence of UPy-SAAP-148GG at the surface. The supramolecular immobilized peptide remains antimicrobially active in dropcast polymer films and can successfully kill (antibiotic-resistant) Staphylococcus aureus, Acinetobacter baumannii, and Escherichia coli. Minor toxicity for human dermal fibroblasts is observed, with a reduced cell attachment after 24 h. Subsequently, a dipcoat coating on titanium implants is developed and tested in vivo in a subcutaneous implant infection mouse model with S. aureus administered locally on the implant before implantation to mimic contamination during surgery. The supramolecular coating containing 5 mol% of UPy-SAAP-148GG significantly prevents colonization of the implant surface as well as of the surrounding tissue, with no signs of toxicity. This shows that supramolecular AMP coatings on titanium are eminently suitable to prevent BAI.

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KW - coatings

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KW - supramolecular biomaterials

KW - titanium

KW - ureido-pyrimidinone

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ER -

Development of an Antimicrobial Peptide SAAP-148-Functionalized Supramolecular Coating on Titanium to Prevent Biomaterial-Associated Infections

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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New Supramolecular Research Findings from Eindhoven University of Technology Outlined (Development of an Antimicrobial Peptide Saap-148-functionalized Supramolecular Coating On Titanium To Prevent Biomaterial-associated Infections)

Cite this

Development of an Antimicrobial Peptide SAAP-148-Functionalized Supramolecular Coating on Titanium to Prevent Biomaterial-Associated Infections

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Press/Media

New Supramolecular Research Findings from Eindhoven University of Technology Outlined (Development of an Antimicrobial Peptide Saap-148-functionalized Supramolecular Coating On Titanium To Prevent Biomaterial-associated Infections)

Cite this