title: Harnessing the multifunctionality in nature: a bioactive agent release system with self-antimicrobial and immunomodulatory properties.
abstract: Major problems with biomedical devices in particular implants located in nonsterile environments concern: (i) excessive immune response to the implant, (ii) development of bacterial biofilms, and (iii) yeast and fungi infections. An original multifunctional coating that addresses all these issues concomitantly is developed. A new exponentially growing polyelectrolyte multilayer film based on polyarginine (PAR) and hyaluronic acid (HA) is designed. The films have a strong inhibitory effect on the production of inflammatory cytokines released by human primary macrophage subpopulations. This could reduce potential chronic inflammatory reaction following implantation. Next, it is shown that PAR, due to its positive charges, has an antimicrobial activity in film format against Staphylococcus aureus for 24 h. In order to have a long-term antimicrobial activity, a precursor nanoscale silver coating is deposited on the surface before adding the PAR/HA films. Moreover, the PAR/HA films can be easily further functionalized by embedding antimicrobial peptides, like catestatin (CAT), a natural host defense peptide. This PAR/HA+CAT film proves to be effective as an antimicrobial coating against yeast and fungi and its cytocompatibility is also assessed. Finally, this all-in-one system constitutes an original strategy to limit inflammation and prevents bacteria, yeast, and fungi infections.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, 11 rue Humann, 67085, Strasbourg, France.|Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000, Strasbourg, France.
authors.forename: Hayriye
authors.initials: H
authors.lastname: Özçelik
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, 11 rue Humann, 67085, Strasbourg, France.|Protip SAS, 8 Place de l'Hôpital, 67000, Strasbourg, France.
authors.forename: Nihal Engin
authors.initials: NE
authors.lastname: Vrana
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Uber 1-3, 68167, Mannheim, Germany.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Gudima
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Uber 1-3, 68167, Mannheim, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Riabov
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Uber 1-3, 68167, Mannheim, Germany.|Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, 36 Lenin Prospekt, Tomsk, 634050, Russia.
authors.forename: Alexei
authors.initials: A
authors.lastname: Gratchev
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, 11 rue Humann, 67085, Strasbourg, France.|Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000, Strasbourg, France.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Haikel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, 11 rue Humann, 67085, Strasbourg, France.|Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000, Strasbourg, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.affiliation: Institut de Physique et Chimie des Matériaux de Strasbourg, UMR 7054 CNRS, 23 rue du Loess, Strasbourg Cedex 2, Strasbourg, 67034, France.
authors.forename: Adele
authors.initials: A
authors.lastname: Carradò
authors.affiliation: Institut de Physique et Chimie des Matériaux de Strasbourg, UMR 7054 CNRS, 23 rue du Loess, Strasbourg Cedex 2, Strasbourg, 67034, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Faerber
authors.affiliation: Institut Charles Sadron, CNRS UPR 22, Strasbourg, 67034, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Roland
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Uber 1-3, 68167, Mannheim, Germany.|Red Cross Blood Service Baden-Württemberg - Hessen, Friedrich-Ebert Str. 107, D-68167, Mannheim, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Klüter
authors.affiliation: Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Uber 1-3, 68167, Mannheim, Germany.|Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, 36 Lenin Prospekt, Tomsk, 634050, Russia.|Red Cross Blood Service Baden-Württemberg - Hessen, Friedrich-Ebert Str. 107, D-68167, Mannheim, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kzhyshkowska
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, 11 rue Humann, 67085, Strasbourg, France.|Institut Charles Sadron, CNRS UPR 22, 23 rue du Lœss, 67034, Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Schaaf
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, 11 rue Humann, 67085, Strasbourg, France.|Faculté de Chirurgie Dentaire, Université de Strasbourg, 1 Place de l'Hôpital, 67000, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lavalle
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002478:Cells, Cultured; D053379:Chromogranin A / Q000737:chemistry / Q000494:pharmacology; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D055767:Immobilized Proteins / Q000737:chemistry / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008856:Microscopy, Fluorescence; D049329:Nanostructures / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D012834:Silver / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D013499:Surface Properties; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D053379:Chromogranin A; D020099:Coated Materials, Biocompatible; D016207:Cytokines; D055767:Immobilized Proteins; D010446:Peptide Fragments; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C109084:chromogranin A (344-364); C015462:polyarginine; D012834:Silver; D007371:Interferon-gamma; D006820:Hyaluronic Acid
keywords: antimicrobial peptides; immunomodulatory properties; implants; multifunctional coatings; polyelectrolyte multilayers