title: Bioactive implant surface with electrochemically bound doxycycline promotes bone formation markers in vitro and in vivo.
abstract: OBJECTIVE
  The objective of this study was to demonstrate a successful binding of Doxy hyclate onto a titanium zirconium alloy surface.
  
  
  METHODS
  The coating was done on titanium zirconium coins in a cathodic polarization setup. The surface binding was analyzed by SEM, SIMS, UV-vis, FTIR and XPS. The in vitro biological response was tested with MC3T3-E1 murine pre-osteoblast cells after 14 days of cultivation and analyzed in RT-PCR. A rabbit tibial model was also used to confirm its bioactivity in vivo after 4 and 8 weeks healing by means of microCT.
  
  
  RESULTS
  A mean of 141 μg/cm(2) of Doxy was found firmly attached and undamaged on the coin. Inclusion of Doxy was documented up to a depth of approximately 0.44 μm by tracing the (12)C carbon isotope. The bioactivity of the coating was documented by an in vitro study with murine osteoblasts, which showed significantly increased alkaline phosphatase and osteocalcin gene expression levels after 14 days of cell culture along with low cytotoxicity. Doxy coated surfaces showed increased bone formation markers at 8 weeks of healing in a rabbit tibial model.
  
  
  CONCLUSIONS
  The present work demonstrates a method of binding the broad spectrum antibiotic doxycycline (Doxy) to an implant surface to improve bone formation and reduce the risk of infection around the implant. We have demonstrated that TiZr implants with electrochemically bound Doxy promote bone formation markers in vitro and in vivo.
authors.affiliation: Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway; Institute of Medical and Polymer Engineering, Chair of Medical Engineering, Technische Universität München, Garching, Germany.
authors.forename: M S
authors.initials: MS
authors.lastname: Walter
authors.affiliation: Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway; Institute of Medical and Polymer Engineering, Chair of Medical Engineering, Technische Universität München, Garching, Germany.
authors.forename: M J
authors.initials: MJ
authors.lastname: Frank
authors.affiliation: Department of Fundamental Biology and Health Sciences, Research Institute on Health Sciences (IUNICS), University of Balearic Islands, Palma de Mallorca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Satué
authors.affiliation: Department of Fundamental Biology and Health Sciences, Research Institute on Health Sciences (IUNICS), University of Balearic Islands, Palma de Mallorca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Monjo
authors.affiliation: Department of Prosthodontics, Institute of Clinical Odontology, University of Oslo, Oslo, Norway.
authors.forename: H J
authors.initials: HJ
authors.lastname: Rønold
authors.affiliation: Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway.
authors.forename: S P
authors.initials: SP
authors.lastname: Lyngstadaas
authors.affiliation: Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway. Electronic address: h.j.haugen@odont.uio.no.
authors.forename: H J
authors.initials: HJ
authors.lastname: Haugen
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D015921:Dental Implants; D004318:Doxycycline / Q000737:chemistry* / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D011817:Rabbits; D013499:Surface Properties; D055114:X-Ray Microtomography
chemical_list: D015921:Dental Implants; D004318:Doxycycline
keywords: Biomolecule binding; Bone formation; Cathodic reduction; Doxycycline; In vivo; SIMS; Surface modification; Titanium zirconium implant; XPS; microCT