Self-defending additively manufactured bone implants bearing silver and copper nanoparticles.
Identifieur interne : 000187 ( Main/Corpus ); précédent : 000186; suivant : 000188Self-defending additively manufactured bone implants bearing silver and copper nanoparticles.
Auteurs : I A J. Van Hengel ; M W A M. Tierolf ; V P M. Valerio ; M. Minneboo ; A C Fluit ; L E Fratila-Apachitei ; I. Apachitei ; A A ZadpoorSource :
- Journal of materials chemistry. B [ 2050-7518 ] ; 2020.
Abstract
Effective preventive measures against implant-associated infection (IAI) are desperately needed. Therefore, the development of self-defending implants with intrinsic antibacterial properties has gained significant momentum. Biomaterials biofunctionalized with silver (Ag) have resulted in effective antibacterial biomaterials, yet regularly induce cytotoxicity. In this study, the use of both Ag and copper (Cu) nanoparticles (NPs) on TiO2 surfaces was investigated to generate antibacterial and osteoconductive biomaterials. Hence, additively manufactured Ti-6Al-4V volume-porous implants were biofunctionalized with plasma electrolytic oxidation (PEO) through the incorporation of varying ratios of Ag and/or Cu NPs in the TiO2 layer covering the implant surface. For all experimental groups, the surface morphology, chemical composition, ion release profile, generation of reactive ion species, antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and ex vivo, as well as the response of pre-osteoblastic MC3T3-E1 cells in metabolic activity and differentiation assays were determined. PEO biofunctionalization resulted in rough and highly porous surfaces that released Ag and Cu ions for 28 days and generated hydroxyl as well as methyl radicals. A strong synergistic bactericidal behavior between Ag and Cu ions was detected, which allowed to decrease the concentration of Ag ions by 10-fold, while maintaining the same level of antibacterial activity. Antibacterial agar diffusion and quantitative assays indicated strong antibacterial activity in vitro for the implants containing Ag and Ag/Cu, while no antibacterial activity was observed for implants bearing only Cu NPs. Moreover, the biofunctionalized implants with ratios of up to 75% Ag and 25% Cu NP totally eradicated all bacteria in an ex vivo model using murine femora. Meanwhile, the biofunctionalized implants did not show any signs of cytotoxicity, while implants bearing only Cu NPs improved the metabolic activity after 7 and 11 days. The biomaterials developed here, therefore, exploit the synergistic behavior of Ag and Cu to simultaneously offer strong antibacterial behavior while fully mitigating the cytotoxicity of Ag against mammalian cells.
DOI: 10.1039/c9tb02434d
PubMed: 31848564
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Tierolf</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Valerio, V P M" sort="Valerio, V P M" uniqKey="Valerio V" first="V P M" last="Valerio">V P M. Valerio</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Minneboo, M" sort="Minneboo, M" uniqKey="Minneboo M" first="M" last="Minneboo">M. Minneboo</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Fluit, A C" sort="Fluit, A C" uniqKey="Fluit A" first="A C" last="Fluit">A C Fluit</name><affiliation><nlm:affiliation>Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Fratila Apachitei, L E" sort="Fratila Apachitei, L E" uniqKey="Fratila Apachitei L" first="L E" last="Fratila-Apachitei">L E Fratila-Apachitei</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Apachitei, I" sort="Apachitei, I" uniqKey="Apachitei I" first="I" last="Apachitei">I. Apachitei</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Zadpoor, A A" sort="Zadpoor, A A" uniqKey="Zadpoor A" first="A A" last="Zadpoor">A A Zadpoor</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:31848564</idno><idno type="pmid">31848564</idno><idno type="doi">10.1039/c9tb02434d</idno><idno type="wicri:Area/Main/Corpus">000187</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000187</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Self-defending additively manufactured bone implants bearing silver and copper nanoparticles.</title><author><name sortKey="Van Hengel, I A J" sort="Van Hengel, I A J" uniqKey="Van Hengel I" first="I A J" last="Van Hengel">I A J. Van Hengel</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Tierolf, M W A M" sort="Tierolf, M W A M" uniqKey="Tierolf M" first="M W A M" last="Tierolf">M W A M. Tierolf</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Valerio, V P M" sort="Valerio, V P M" uniqKey="Valerio V" first="V P M" last="Valerio">V P M. Valerio</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Minneboo, M" sort="Minneboo, M" uniqKey="Minneboo M" first="M" last="Minneboo">M. Minneboo</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Fluit, A C" sort="Fluit, A C" uniqKey="Fluit A" first="A C" last="Fluit">A C Fluit</name><affiliation><nlm:affiliation>Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Fratila Apachitei, L E" sort="Fratila Apachitei, L E" uniqKey="Fratila Apachitei L" first="L E" last="Fratila-Apachitei">L E Fratila-Apachitei</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Apachitei, I" sort="Apachitei, I" uniqKey="Apachitei I" first="I" last="Apachitei">I. Apachitei</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author><author><name sortKey="Zadpoor, A A" sort="Zadpoor, A A" uniqKey="Zadpoor A" first="A A" last="Zadpoor">A A Zadpoor</name><affiliation><nlm:affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of materials chemistry. B</title><idno type="eISSN">2050-7518</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Effective preventive measures against implant-associated infection (IAI) are desperately needed. Therefore, the development of self-defending implants with intrinsic antibacterial properties has gained significant momentum. Biomaterials biofunctionalized with silver (Ag) have resulted in effective antibacterial biomaterials, yet regularly induce cytotoxicity. In this study, the use of both Ag and copper (Cu) nanoparticles (NPs) on TiO2 surfaces was investigated to generate antibacterial and osteoconductive biomaterials. Hence, additively manufactured Ti-6Al-4V volume-porous implants were biofunctionalized with plasma electrolytic oxidation (PEO) through the incorporation of varying ratios of Ag and/or Cu NPs in the TiO2 layer covering the implant surface. For all experimental groups, the surface morphology, chemical composition, ion release profile, generation of reactive ion species, antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and ex vivo, as well as the response of pre-osteoblastic MC3T3-E1 cells in metabolic activity and differentiation assays were determined. PEO biofunctionalization resulted in rough and highly porous surfaces that released Ag and Cu ions for 28 days and generated hydroxyl as well as methyl radicals. A strong synergistic bactericidal behavior between Ag and Cu ions was detected, which allowed to decrease the concentration of Ag ions by 10-fold, while maintaining the same level of antibacterial activity. Antibacterial agar diffusion and quantitative assays indicated strong antibacterial activity in vitro for the implants containing Ag and Ag/Cu, while no antibacterial activity was observed for implants bearing only Cu NPs. Moreover, the biofunctionalized implants with ratios of up to 75% Ag and 25% Cu NP totally eradicated all bacteria in an ex vivo model using murine femora. Meanwhile, the biofunctionalized implants did not show any signs of cytotoxicity, while implants bearing only Cu NPs improved the metabolic activity after 7 and 11 days. The biomaterials developed here, therefore, exploit the synergistic behavior of Ag and Cu to simultaneously offer strong antibacterial behavior while fully mitigating the cytotoxicity of Ag against mammalian cells.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">31848564</PMID><DateRevised><Year>2020</Year><Month>08</Month><Day>28</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">2050-7518</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><Issue>8</Issue><PubDate><Year>2020</Year><Month>02</Month><Day>26</Day></PubDate></JournalIssue><Title>Journal of materials chemistry. B</Title><ISOAbbreviation>J Mater Chem B</ISOAbbreviation></Journal><ArticleTitle>Self-defending additively manufactured bone implants bearing silver and copper nanoparticles.</ArticleTitle><Pagination><MedlinePgn>1589-1602</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1039/c9tb02434d</ELocationID><Abstract><AbstractText>Effective preventive measures against implant-associated infection (IAI) are desperately needed. Therefore, the development of self-defending implants with intrinsic antibacterial properties has gained significant momentum. Biomaterials biofunctionalized with silver (Ag) have resulted in effective antibacterial biomaterials, yet regularly induce cytotoxicity. In this study, the use of both Ag and copper (Cu) nanoparticles (NPs) on TiO2 surfaces was investigated to generate antibacterial and osteoconductive biomaterials. Hence, additively manufactured Ti-6Al-4V volume-porous implants were biofunctionalized with plasma electrolytic oxidation (PEO) through the incorporation of varying ratios of Ag and/or Cu NPs in the TiO2 layer covering the implant surface. For all experimental groups, the surface morphology, chemical composition, ion release profile, generation of reactive ion species, antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and ex vivo, as well as the response of pre-osteoblastic MC3T3-E1 cells in metabolic activity and differentiation assays were determined. PEO biofunctionalization resulted in rough and highly porous surfaces that released Ag and Cu ions for 28 days and generated hydroxyl as well as methyl radicals. A strong synergistic bactericidal behavior between Ag and Cu ions was detected, which allowed to decrease the concentration of Ag ions by 10-fold, while maintaining the same level of antibacterial activity. Antibacterial agar diffusion and quantitative assays indicated strong antibacterial activity in vitro for the implants containing Ag and Ag/Cu, while no antibacterial activity was observed for implants bearing only Cu NPs. Moreover, the biofunctionalized implants with ratios of up to 75% Ag and 25% Cu NP totally eradicated all bacteria in an ex vivo model using murine femora. Meanwhile, the biofunctionalized implants did not show any signs of cytotoxicity, while implants bearing only Cu NPs improved the metabolic activity after 7 and 11 days. The biomaterials developed here, therefore, exploit the synergistic behavior of Ag and Cu to simultaneously offer strong antibacterial behavior while fully mitigating the cytotoxicity of Ag against mammalian cells.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>van Hengel</LastName><ForeName>I A J</ForeName><Initials>IAJ</Initials><Identifier Source="ORCID">0000-0002-7171-257X</Identifier><AffiliationInfo><Affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tierolf</LastName><ForeName>M W A M</ForeName><Initials>MWAM</Initials><AffiliationInfo><Affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Valerio</LastName><ForeName>V P M</ForeName><Initials>VPM</Initials><AffiliationInfo><Affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Minneboo</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fluit</LastName><ForeName>A C</ForeName><Initials>AC</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fratila-Apachitei</LastName><ForeName>L E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Apachitei</LastName><ForeName>I</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zadpoor</LastName><ForeName>A A</ForeName><Initials>AA</Initials><Identifier Source="ORCID">0000-0003-3234-2112</Identifier><AffiliationInfo><Affiliation>Additive Manufacturing Laboratory, Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, The Netherlands. i.a.j.vanhengel@tudelft.nl.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Mater Chem B</MedlineTA><NlmUniqueID>101598493</NlmUniqueID><ISSNLinking>2050-750X</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>12</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>12</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>12</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31848564</ArticleId><ArticleId IdType="doi">10.1039/c9tb02434d</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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