Kyle M Kovach1, Doe W Kumsa2, Vishnupriya Srivastava1, Eric M Hudak3, Darrel F Untereker4, Shawn C Kelley4, Horst A von Recum1, Jeffrey R Capadona5. 1. 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. 2. Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Jr. Drive, Wickenden Bldg., Cleveland, OH 44106, USA. 3. Department of Research & Technology, Advanced Bionics LLC, 28515 Westinghouse Place, Valencia, CA 91355, USA. 4. Medtronic plc, Science and Technology, 710 Medtronic Parkway, Minneapolis, MN 55432, USA. 5. 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.
Abstract
BACKGROUND: 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. NEW METHOD: 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. RESULTS: 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. COMPARISON WITH EXISTING METHODS: To our knowledge, there does not exist a simple, in vitro assay system for assessing the cytotoxicity of Pt liberated from stimulating neural electrodes. CONCLUSIONS: 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. Published by Elsevier B.V.
BACKGROUND: 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. NEW METHOD: 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. RESULTS: 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. COMPARISON WITH EXISTING METHODS: To our knowledge, there does not exist a simple, in vitro assay system for assessing the cytotoxicity of Pt liberated from stimulating neural electrodes. CONCLUSIONS: 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. Published by Elsevier B.V.
Authors: Kevin C Spencer; Jay C Sy; Khalil B Ramadi; Ann M Graybiel; Robert Langer; Michael J Cima Journal: Sci Rep Date: 2017-05-16 Impact factor: 4.379