title: Macrophage responses to implants: prospects for personalized medicine.
abstract: Implants, transplants, and implantable biomedical devices are mainstream solutions for a wide variety of human pathologies. One of the persistent problems around nondegradable metallic and polymeric implants is failure of macrophages to resolve the inflammation and their tendency to stay in a state, named "frustrated phagocytosis." During the initial phase, proinflammatory macrophages induce acute reactions to trauma and foreign materials, whereas tolerogenic anti-inflammatory macrophages control resolution of inflammation and induce the subsequent healing stage. However, implanted materials can induce a mixed pro/anti-inflammatory phenotype, supporting chronic inflammatory reactions accompanied by microbial contamination and resulting in implant failure. Several materials based on natural polymers for improved interaction with host tissue or surfaces that release anti-inflammatory drugs/bioactive agents have been developed for implant coating to reduce implant rejection. However, no definitive, long-term solution to avoid adverse immune responses to the implanted materials is available to date. The prevention of implant-associated infections or chronic inflammation by manipulating the macrophage phenotype is a promising strategy to improve implant acceptance. The immunomodulatory properties of currently available implant coatings need to be improved to develop personalized therapeutic solutions. Human primary macrophages exposed to the implantable materials ex vivo can be used to predict the individual's reactions and allow selection of an optimal coating composition. Our review describes current understanding of the mechanisms of macrophage interactions with implantable materials and outlines the prospects for use of human primary macrophages for diagnostic and therapeutic approaches to personalized implant therapy.
authors.affiliation: *Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia; Protip SAS, Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France julia.kzhyshkowska@medma.uni-heidelberg.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Kzhyshkowska
authors.affiliation: *Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia; Protip SAS, Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Gudima
authors.affiliation: *Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia; Protip SAS, Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Riabov
authors.affiliation: *Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia; Protip SAS, Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Dollinger
authors.affiliation: *Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia; Protip SAS, Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lavalle
authors.affiliation: *Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia; Protip SAS, Strasbourg, France; Institut National de la Santé et de la Recherche Médicale, INSERM Unité 1121, Strasbourg, France; and Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: Nihal Engin
authors.initials: NE
authors.lastname: Vrana
mesh_terms: D000818:Animals; D020099:Coated Materials, Biocompatible; D005549:Foreign-Body Reaction / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis; D057285:Precision Medicine / Q000379:methods*; D019736:Prostheses and Implants / Q000009:adverse effects*; D013499:Surface Properties
chemical_list: D020099:Coated Materials, Biocompatible
keywords: biomarker; biomaterial; coating; cytokine; titanium