Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF‐coated electrodes

Abstract

Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day SGN explant assay found that neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p < 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants.

Stable release of BDNF from the fibroblast cell line NIH3T3 grown on silicone elastomers enhances survival of spiral ganglion cells in vitro and in vivo

“…In comparison to these data, cannula-or tube-based BDNF delivery systems needed significantly higher concentrations ranging from 50 ng/ml (Miller et al, 1997) to 100 ng/ml (Agterberg et al, 2009;McGuinness and Shepherd, 2005;Shepherd et al, 2008;Shinohara et al, 2002) to rescue SGC and regenerate their neurites. This observation is supported by Evans et al (2009) using cochlear electrodes coated with Fig. 7.…”

“…One option could be the use of the CI as drug delivery device (Evans et al, 2009;Richardson et al, 2009;Huang et al, 2010). However, this drug delivery system is limited by the amount of growth factors that can be loaded on the implant surface.…”

Skeletal myotube formation enhanced by electrospun polyurethane carbon nanotube scaffolds

“…9,10 Electrically conducting materials have also been used to deliver electrical signals to cells and to alter key cell behaviors. Electrically conductive materials, such as polypyrrole, 11,12 polyaniline, 13 and poly(3,4-ethylenedioxythiophene), 14 have been shown to affect cell behavior when electrically stimulated. In addition, nanocomposites of polylactic acid and multiwalled carbon nanotubes (MWNT) have been reported to promote osteoblast differentiation in vitro, achieving a 46% increase in calcium deposition in the extracellular matrix and a 300% greater expression of various genes (such as osteopontin, osteonectin mRNA, and osteocalcin) when an alternating current (10 µA at 10 Hz of electrical stimulation for six hours daily for 21 consecutive days) was applied to the polylactic acid-MWNT composites.…”

Brain-Derived Neurotrophic Factor Modulates Auditory Function in the Hearing Cochlea

“…Neurotrophins have been pivotal in research directed towards achieving this aim. These proteins have been shown to rescue auditory neurons from cell death after sensorineural hearing loss (Staecker et al 1996(Staecker et al , 1998Miller et al 1997;Gillespie et al 2004) and to promote the regrowth of the peripheral dendrites of surviving neurons (Wise et al 2005;Miller et al 2007;Evans et al 2009) with both effects being desirable to increase electrode specificity (Miller et al 2007; O' Leary et al 2009). …”