title: Antimicrobial photodynamic therapy suppresses dental plaque formation in healthy adults: a randomized controlled clinical trial.
abstract: BACKGROUND
  Oral care is important for oral and systemic health, especially for elderly institutionalized individuals and compromised patients. However, conventional mechanical plaque control is often difficult for these patients because of the pain or the risk of aspiration. Although antimicrobial photodynamic therapy (aPDT), which is considered an alternative or adjunct to mechanical approaches, has potential application as a less stressful method of daily plaque control, no clinical application of this technique has been reported.
  
  
  METHODS
  We investigated the inhibitory effect of a combination of toluidine blue O (TBO), and a red light-emitting diode (LED) on dental plaque formation in healthy volunteers. The optimal concentration of TBO was determined in preliminary in vitro experiments to evaluate the bactericidal effect of aPDT on Streptococcus oralis and to clarify its safety in fibroblast cells. To survey the mechanism of TBO-mediated aPDT, the quality and quantity of reactive oxygen species (ROS) generated during aPDT were also examined using electron spin resonance (ESR) spectroscopy. Subsequently, the inhibitory effect of aPDT on dental plaque formation was investigated in eleven subjects as a clinical pilot study. The right or left mandibular premolars were randomly assigned to the treatment (with aPDT) or control (without aPDT) groups. In total, aPDT was applied six times (twice per day) to the teeth in the test group over a period of four days. On the fourth day, the study concluded and the analyses were performed.
  
  
  RESULTS
  A combination of 500 or 1000 μg/ml TBO and LED irradiation for 20 s significantly decreased the number of colony forming units of Streptococcus oralis. The cytotoxicity of aPDT was comparable to that of standard antiseptics used in the oral cavity. Hydroxyl radicals were detected by ESR analysis, but singlet oxygen was not. A randomized controlled trial demonstrated that aPDT with 1000 μg/ml TBO and red LED irradiation significantly suppressed dental plaque formation without harming teeth or the surrounding tissues.
  
  
  CONCLUSIONS
  aPDT has the potential to be a promising novel technical modality for dental plaque control.
  
  
  BACKGROUND
  This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (number UMIN000012504).
authors.forename: Akiko
authors.initials: A
authors.lastname: Ichinose-Tsuno
authors.affiliation: Department of Periodontology, Graduate school of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8549, Japan. aoperi@tmd.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Aoki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Teruo
authors.initials: T
authors.lastname: Kirikae
authors.forename: Takuro
authors.initials: T
authors.lastname: Shimbo
authors.forename: Masaichi-Chang-Il
authors.initials: MC
authors.lastname: Lee
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yoshino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Maruoka
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Itoh
authors.forename: Isao
authors.initials: I
authors.lastname: Ishikawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Izumi
mesh_terms: D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use / Q000633:toxicity; D000891:Anti-Infective Agents, Local / Q000633:toxicity; D058491:Bacterial Load / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003124:Colorimetry; D003773:Dental Plaque / Q000382:microbiology / Q000517:prevention & control*; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D017665:Hydroxyl Radical / Q000032:analysis; D008422:Materials Testing; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D023861:Photography, Dental; D017319:Photosensitizing Agents / Q000627:therapeutic use / Q000633:toxicity; D010865:Pilot Projects; D017382:Reactive Oxygen Species / Q000032:analysis; D016037:Single-Blind Method; D019533:Streptococcus oralis / Q000187:drug effects; D014048:Tolonium Chloride / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D014048:Tolonium Chloride; D017665:Hydroxyl Radical