The Synergistic Effects of Gold Particles and Dexamethasone on the Electrochemical and Biological Performance of PEDOT Neural Interfaces

Abstract

Although neural devices have shown efficacy in the treatment of neurodegenerative diseases, their functionality is limited by the inflammatory state and glial scar formation associated with chronic implantation. The aim of this study was to investigate neural electrode performance following functionalization with an anti-inflammatory coating derived from a conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) matrix doped with dexamethasone (Dex) and decorated with Au particles. Pristine PEDOT, PEDOT-Dex and their gold-decorated analogues (PEDOT/Au and PEDOT-Dex/Au) were formulated by electrochemical deposition and characterized with respect to electrode electrochemical properties, surface morphology and biocompatibility towards primary neural cells. Through a process of gold deposition, it was possible to eliminate the initial burst release observed in PEDOT-Dex and maintain a stable, stepwise increase in Dex elution over 7 days. The released amounts of Dex exceeded the concentrations considered as therapeutic for both PEDOT-Dex and PEDOT-Dex/Au. The results clearly indicated that the presence of either Dex or Au particles facilitated the outgrowth of neurites. Finally, it was shown that the application of composite materials, such as PEDOT-Dex/Au, is an efficient way to improve the efficacy of neural interfaces in vitro.

Keywords: PEDOT; dexamethasone; gold particles; neural interfaces.

Figure 1

Electrochemical properties of poly(3,4-ethylenedioxythiphene) (PEDOT)-functionalized Pt electrodes. (A) Cyclic voltammetric (CV) curves of the final cycles of the electropolymerization process of EDOT (15 mM) formed in 1× phosphate buffered saline (PBS) or in 1× PBS in the presence of 10 mM Dex, together with a CV of a bare Pt electrode. (B) CV curves of the process of gold deposition from 2 mM HAuCl₄ aqueous solution in 1× PBS. (C) Bode plot expression of impedance modulus and (D) Bode plot expression of the phase angle of PEDOT, PEDOT/Au, PEDOT-Dex, PEDOT-Dex/Au and a bare Pt electrode, collected in 1× PBS.

Figure 2

Surface characteristics of PEDOT functionalized Pt electrodes. (A) Fourier transform-infrared (FTIR) spectra and (B) macroscopic images of Dex, pristine PEDOT, PEDOT/Au, PEDOT-Dex and PEDOT-Dex/Au; grey regions in FTIR spectra indicate signals characteristic for Dex that can be found in PEDOT-Dex and PEDOT-Dex/Au.

Figure 3

Surface morphology of Dex-functionalized PEDOT and PEDOT composite matrices. (A) Scanning electron microscope (SEM) images of PEDOT, PEDOT-Dex and PEDOT/Au matrices. (B) Size distribution of gold particles and (C) energy-dispersive X-ray (EDS) spectrum of a region of interest depicted in the SEM image.

Figure 4

Dex release from Dex-doped PEDOT and PEDOT composite substrates. (A) Drug elution profiles of spontaneous Dex release from PEDOT-Dex and PEDOT-Dex/Au functionalized electrodes. Dots are the experimental values and lines represent the corresponding fitted curves calculated by means of Avrami’s equation. (B) Macroscopic images of PEDOT-Dex and PEDOT-Dex/Au functionalized electrodes after performing the elution experiment.

Figure 5

Biological properties of PEDOT functional coatings and bare Pt substrates. (A) Fluorescent images of primary ventral mesencephalic (VM) mixed cell population cultured for seven days on magnetron sputtered Pt, PEDOT, PEDOT/Au, PEDOT-Dex and PEDOT-Dex/Au; neurons are visualized by anti β-tubulin III (red), astrocyte cells by anti-glial fibrillary acidic protein, GFAP stain (green) and nuclei by 4′,6-diamidino-2-phenylindole, DAPI (blue). (B) The average neurite length and (C) cell density analysis of astrocyte and neuron presence on each of the experimental and control group; ★ = p < 0.05, N = 3.