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.

Highlights

  • The ST was replaced with SBF (1.5), and the pins were kept at 50 °C for 1 week, with daily changes of the SBF (1.5)

  • The resulting HAp-film-coated Ti (HAp-Ti) pins were immersed in an IP6 solution (1000 ppm, 5 cm3) at 50 °C for 1 day, to modify the HAp film surface (HAp-IP6-Ti)

  • Surface evaluation of the implant coated with ionic silver bound to HAp film via IP6-film chelation

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Summary

Introduction

® Ag+ on the IP6-modified surface of the HAp film by chelation. (b) Molecular model of IP6 drawn by Spartan (Wavefunction, Inc.; white: H, grey: C, red: O, Orange: P). (c) Image of the electrostatic potential of model (b); red indicates the presence of electrons at high density. (d) Structural formula of IP6 by Barré and Courtois; twelve OH groups in the IP6 form chelate-bonding sites for metal ions (ex, Ag+, Ca2+, Zn2+). (e) Diagram showing the coating of a Ti implant with HAp, the modification of the HAp surface with IP6, and the application of a layer of immobile ionic silver via IP6’s chelate-binding ability (HAp-IP6-Ag+ Ti). (f,g) Scanning electron microscopy (SEM) images of (f) the pure Ti substrate, and (g) HAp particles precipitated on the Ti substrate to form a layer. (h–j) SEM images of HAp-IP6-Ag+(1, 5, 10)-Ti pins, respectively. (i,j) Arrows indicate cubeshaped particles (arrows) deposited on the HAp layer. (c) Image of the electrostatic potential of model (b); red indicates the presence of electrons at high density. (e) Diagram showing the coating of a Ti implant with HAp, the modification of the HAp surface with IP6, and the application of a layer of immobile ionic silver via IP6’s chelate-binding ability (HAp-IP6-Ag+ Ti). (f,g) Scanning electron microscopy (SEM) images of (f) the pure Ti substrate, and (g) HAp particles precipitated on the Ti substrate to form a layer. Devices with good in vitro antibacterial effects do not necessarily elicit the same results at an infection site in vivo. To maintain its antibacterial activity in vivo, the silver must remain in an ionic state and be stably bound to the implant surface.

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