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Temporal Attenuation of Iodine Content and its Effect on the Antibacterial Activity of Iodine-Supported Titanium Implants

Takashi Kato, Toshiharu Shirai, Norio Yamamoto, Hideji Nishida, Katsuhiro Hayashi, Akihiko Takeuchi, Shinji Miwa, Kaori Ohtani and Hiroyuki Tsuchiya

Infections related to orthopedic implants often require prolonged therapy and complex interventions; accordingly, the development of implants with a low risk of infection is a high priority. Iodine-supported titanium implants with antibacterial activity are safe and effective for prophylaxis against implant-related infections. However, temporal changes in the iodine content of implants and the effects on antibacterial activity have not been investigated. In vitro antibacterial activity against Staphylococcus aureus and Escherichia coli was investigated using implants with various iodine contents (0%, 20%, 50%, 60%, and 100%, where 100% corresponds to 13 μg/cm2 iodine based on current implants in clinical use). Temporal changes in iodine for 10–12 μg/cm2 iodine-supplemented titanium implants were also investigated in vitro and in vivo using rabbit models (subcutaneous soft tissue, intra-articular and endo-osseous sites). The minimum effective iodine concentration required for antibacterial activity and the residual iodine after 1 year of implantation were determined. Pure titanium implants and implants with a 0% oxide layer did not exhibit antibacterial activity. Titanium implants supplemented with 20%, 50%, 80%, and 100% iodine showed in vitro antibacterial activity that varied in a dose-dependent and duration-dependent manner. Implants with ≥ 20% iodine achieved complete clearance of S. aureus and E. coli colonies by 24 h of incubation. In vitro and in vivo experiments showed a similar temporal pattern of initially rapid and subsequently slow attenuation of iodine in the implants, with approximately 30% of the initial iodine content remaining at 1 year. Implants with iodine contents of ≥ 20% demonstrated sufficient antibacterial activity, indicating that current iodine-supported titanium implants possess adequate antibacterial activity to prevent implant-related infections, even after 1 year of implantation. These results support the clinical use of iodine-supported titanium implants to prevent orthopedic implant-related infections.