title: Cytotoxic effect of galvanically coupled magnesium-titanium particles.
abstract: Recent work has shown that reduction reactions at metallic biomaterial surfaces can induce significant killing of cells in proximity to the surface. To exploit this phenomenon for therapeutic purposes, for example, for cancer tumor killing or antibacterial effects (amongst other applications), magnesium metal particles, galvanically coupled to titanium by sputtering, have been evaluated for their cell-killing capability (i.e. cytotoxicity). Magnesium (Mg) particles large enough to prevent particle phagocytosis were investigated, so that only electrochemical reactions, and not particle toxicity per se, caused cytotoxic effects. Titanium (Ti) coated magnesium particles, as well as magnesium-only particles were introduced into MC3T3-E1 mouse pre-osteoblast cell cultures over a range of particle concentrations, and cells were observed to die in a dosage-dependent manner. Ti-coated magnesium particles killed more cells at lower particle concentration than magnesium alone (P<0.05), although the pH measured for magnesium and magnesium-titanium had no significant difference at similar particle concentrations. Complete cell killing occurred at 750μg/ml and 1500μg/ml for Mg-Ti and Mg, respectively. Thus, this work demonstrates that galvanically coupled Mg-Ti particles have a significant cell killing capability greater than Mg alone. In addition, when the pH associated with complete killing with particles was created using NaOH only (no particles), then the percentage of cells killed was significantly less (P<0.05). Together, these findings show that pH is not the sole factor associated with cell killing and that the electrochemical reactions, including the reduction reactions, play an important role. Reduction reactions on galvanically coupled Mg-Ti and Mg particles may generate reactive oxygen intermediates that are able to kill cells in close proximity to the particles and this approach may lead to potential therapies for infection and cancer.
  
  
  CONCLUSIONS
  This paper demonstrates that during active corrosion of both Mg and Mg-Ti particles cells cultured with the particles are killed in a dose-dependent particle concentration fashion. Additionally, galvanically-coupled magnesium-titanium microparticles kill cells more effectively than magnesium particles alone. The killing effect was shown to not be due to pH shifts since no differences were seen for different particle types and pH adjusted medium without particles did not exhibit the same level of killing. The significance of this work is the recognition of this killing effect with Mg particles and the potential therapeutic applications in infection control and cancer treatment that this process may provide.
authors.affiliation: Department of Biomedical and Chemical Engineering, L.C. Smith College of Engineering and Computer Science, Syracuse University, Syracuse, New York 13244, USA; Syracuse Biomaterials Institute, Syracuse University, Syracuse, New York 13244, USA. Electronic address: jkim90@syr.edu.
authors.forename: Jua
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biomedical and Chemical Engineering, L.C. Smith College of Engineering and Computer Science, Syracuse University, Syracuse, New York 13244, USA; Syracuse Biomaterials Institute, Syracuse University, Syracuse, New York 13244, USA; Institute of Medical and Biological Engineering, University of Leeds, Leeds, UK. Electronic address: gilbert@syr.edu.
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D002460:Cell Line; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007239:Infections / Q000188:drug therapy / Q000378:metabolism; D008274:Magnesium / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003603:Cytotoxins; D014025:Titanium; D008274:Magnesium
keywords: Cytotoxicity; Galvanic Corrosion; Magnesium alloy; Oxidation and reduction reactions; Reactive oxygen species