title: High-throughput in vitro assay to evaluate the cytotoxicity of liberated platinum compounds for stimulating neural electrodes.
abstract: It is currently unclear how the platinum (Pt) species released from platinum-containing stimulating electrodes may affect the health of the surrounding tissue. This study develops an effective system to assess the cytotoxicity of any electrode-liberated Pt over a short duration, to screen systems before future in vivo testing.
  
  
  
  A platinum electrode was stimulated for two hours under physiologically relevant conditions to induce the liberation of Pt species. The total concentration of liberated Pt species was quantified and the concentration found was used to develop a range of Pt species for our model system comprised of microglia and neuron-like cells.
  
  
  
  Under our stimulation conditions (k=2.3, charge density of 57.7μC/cm2), Pt was liberated to a concentration of 1ppm. Interestingly, after 24h of Pt exposure, the dose-dependent cytotoxicity plots revealed that cell death became statistically significant at 10ppm for microglia and 20ppm for neuronal cells. However, in neuron-like cell cultures, concentrations above 1ppm resulted in significant neurite loss after 24h.
  
  
  
  To our knowledge, there does not exist a simple, in vitro assay system for assessing the cytotoxicity of Pt liberated from stimulating neural electrodes.
  
  
  
  This work describes a simple model assay that is designed to be applicable to almost any electrode and stimulation system where the electrode is directly juxtaposed to the neural target. Based on the application, the duration of stimulation and Pt exposure may be varied.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr. Drive, Wickenden Bldg., Cleveland, OH 44106, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Blvd, 151W/APT, Cleveland, OH 44106, USA.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Kovach
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr. Drive, Wickenden Bldg., Cleveland, OH 44106, USA.
authors.forename: Doe W
authors.initials: DW
authors.lastname: Kumsa
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr. Drive, Wickenden Bldg., Cleveland, OH 44106, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Blvd, 151W/APT, Cleveland, OH 44106, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Research & Technology, Advanced Bionics LLC, 28515 Westinghouse Place, Valencia, CA 91355, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Hudak
authors.affiliation: Medtronic plc, Science and Technology, 710 Medtronic Parkway, Minneapolis, MN 55432, USA.
authors.forename: Darrel F
authors.initials: DF
authors.lastname: Untereker
authors.affiliation: Medtronic plc, Science and Technology, 710 Medtronic Parkway, Minneapolis, MN 55432, USA.
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Kelley
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr. Drive, Wickenden Bldg., Cleveland, OH 44106, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Blvd, 151W/APT, Cleveland, OH 44106, USA.
authors.forename: Horst A
authors.initials: HA
authors.lastname: von Recum
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr. Drive, Wickenden Bldg., Cleveland, OH 44106, USA; Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Blvd, 151W/APT, Cleveland, OH 44106, USA. Electronic address: jeffrey.capadona@case.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Capadona
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002461:Cell Line, Transformed; D017077:Culture Media, Conditioned / Q000633:toxicity; D003603:Cytotoxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004566:Electrodes / Q000009:adverse effects*; D051379:Mice; D017628:Microglia / Q000737:chemistry / Q000187:drug effects*; D009046:Motor Neurons / Q000187:drug effects*; D017671:Platinum Compounds / Q000633:toxicity*
chemical_list: D017077:Culture Media, Conditioned; D003603:Cytotoxins; D017671:Platinum Compounds
keywords: Cytotoxicity; Electrode; Microglia; Neuron; Neurostimulation; Platinum