title: In vitro and in vivo characterization of antibacterial activity and biocompatibility: a study on silver-containing phosphonate monolayers on titanium.
abstract: Infections associated with implanted medical devices are a major cause of nosocomial infections, with serious medical and economic repercussions. A variety of silver-containing coatings have been proposed to decrease the risk of infection by hindering bacterial adhesion and biofilm formation. However, the therapeutic range of silver is relatively narrow and it is important to minimize the amount of silver in the coatings, in order to keep sufficient antibacterial activity without inducing cytotoxicity. In this study, the antibacterial efficiency and biocompatibility of nanocoatings with minimal silver loading (∼0.65 nmol cm(-2)) was evaluated in vitro and in vivo. Titanium substrates were coated by grafting mercaptododecylphosphonic acid (MDPA) monolayers followed by post-reaction with AgNO3. The MDPA/AgNO3 nanocoatings significantly inhibited Escherichia coli and Staphylococcus epidermidis adhesion and biofilm formation in vitro, while allowing attachment and proliferation of MC3T3-E1 preosteoblasts. Moreover, osteogenic differentiation of MC3T3 cells and murine mesenchymal stem cells was not affected by the nanocoatings. Sterilization by ethylene oxide did not alter the antibacterial activity and biocompatibility of the nanocoatings. After subcutaneous implantation of the materials in mice, we demonstrated that MDPA/AgNO3 nanocoatings exhibit significant antibacterial activity and excellent biocompatibility, both in vitro and in vivo, after postoperative seeding with S. epidermidis. These results confirm the interest of coating strategies involving subnanomolar amounts of silver exposed at the extreme surface for preventing bacterial adhesion and biofilm formation on metallic or ceramic medical devices without compromising their biocompatibility.
authors.affiliation: Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-UM1-ENSCM, Université de Montpellier 2, 34095 Montpellier, France.
authors.forename: Carmen-Mihaela
authors.initials: CM
authors.lastname: Tîlmaciu
authors.affiliation: Inserm U844, Hôpital Saint-Eloi, Montpellier F-34295, France; Université Montpellier1, UFR de Médecine, Montpellier F-34967, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Mathieu
authors.affiliation: Inserm U1047, Université Montpellier 1, UFR de Médecine, Nîmes, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lavigne
authors.affiliation: Inserm U844, Hôpital Saint-Eloi, Montpellier F-34295, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Toupet
authors.affiliation: Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-UM1-ENSCM, Université de Montpellier 2, 34095 Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Guerrero
authors.affiliation: Institut de Science des Matériaux de Mulhouse, UMR 7361 CNRS, 68057 Mulhouse Cedex, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ponche
authors.affiliation: Science et Surface, Centre Scientifique Auguste Moiroux, 64 chemin des Mouilles, 69134 Ecully Cedex, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Amalric
authors.affiliation: Inserm U844, Hôpital Saint-Eloi, Montpellier F-34295, France; Université Montpellier1, UFR de Médecine, Montpellier F-34967, France. Electronic address: daniele.noel@inserm.fr.
authors.forename: Danièle
authors.initials: D
authors.lastname: Noël
authors.affiliation: Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-UM1-ENSCM, Université de Montpellier 2, 34095 Montpellier, France. Electronic address: hubert.mutin@univ-montp2.fr.
authors.forename: P Hubert
authors.initials: PH
authors.lastname: Mutin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D005027:Ethylene Oxide / Q000494:pharmacology; D007477:Ions; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects; D056951:Photoelectron Spectroscopy; D012834:Silver / Q000494:pharmacology*; D012996:Solutions; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013242:Sterilization; D014025:Titanium / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D007477:Ions; D063065:Organophosphonates; D012996:Solutions; D012834:Silver; D014025:Titanium; D005027:Ethylene Oxide
keywords: Antibacterial; Biocompatibility; Biofilm; Cytotoxicity; Monolayer