title: A novel hydroxyapatite film coated with ionic silver via inositol hexaphosphate chelation prevents implant-associated infection.
abstract: Various silver-coated implants have been developed to prevent implant-associated infections, and have shown dramatic effects in vitro. However, the in vivo results have been inconsistent. Recent in vitro studies showed that silver exerts antibacterial activity by mediating the generation of reactive oxygen species in the presence of oxygen. To maintain its antibacterial activity in vivo, the silver should remain in an ionic state and be stably bound to the implant surface. Here, we developed a novel bacteria-resistant hydroxyapatite film in which ionic silver is immobilized via inositol hexaphosphate chelation using a low-heat immersion process. This bacteria-resistant coating demonstrated significant antibacterial activity both in vitro and in vivo. In a murine bioluminescent osteomyelitis model, no bacteria were detectable 21 days after inoculation with S. aureus and placement of this implant. Serum interleukin-6 was elevated in the acute phase in this model, but it was significantly lower in the ionic-silver group than the control group on day 2. Serum C-reactive protein remained significantly higher in the control group than the ionic-silver group on day 14. Because this coating is produced by a low-heat immersion process, it can be applied to complex structures of various materials, to provide significant protection against implant-associated infections.
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.
authors.forename: Haruki
authors.initials: H
authors.lastname: Funao
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.|Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, JAPAN.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nagai
authors.affiliation: Department of Pathology, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.
authors.forename: Aya
authors.initials: A
authors.lastname: Sasaki
authors.affiliation: Department of Applied Chemistry, School of Science and Technology, Meiji University, Kawasaki, Kanagawa, JAPAN.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hoshikawa
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Pathology, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.|Department of Pathology and Oncology, School of Medicine, Juntendo University, Bunkyo, Tokyo, JAPAN.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.|Laboratory for Immune Cell Systems, RIKEN Centre for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, JAPAN.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Applied Chemistry, School of Science and Technology, Meiji University, Kawasaki, Kanagawa, JAPAN.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Aizawa
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.
authors.forename: Morio
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku, Tokyo, JAPAN.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000494:pharmacology; D004195:Disease Models, Animal; D017886:Durapatite / Q000737:chemistry*; D005269:Femur / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D007477:Ions / Q000737:chemistry; D008163:Luminescent Measurements; D051379:Mice; D010019:Osteomyelitis / Q000097:blood / Q000517:prevention & control / Q000662:veterinary; D010833:Phytic Acid / Q000737:chemistry*; D019736:Prostheses and Implants; D012834:Silver / Q000737:chemistry*; D013054:Spectrophotometry, Atomic; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D002614:Chelating Agents; D020099:Coated Materials, Biocompatible; D015850:Interleukin-6; D007477:Ions; D012834:Silver; D010833:Phytic Acid; D002097:C-Reactive Protein; D017886:Durapatite