title: 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.
authors.affiliation: Department of Otolaryngology, The University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Evans
authors.forename: Brianna C
authors.initials: BC
authors.lastname: Thompson
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Wallace
authors.forename: Rodney
authors.initials: R
authors.lastname: Millard
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Leary
authors.forename: Graeme M
authors.initials: GM
authors.lastname: Clark
authors.forename: Robert K
authors.initials: RK
authors.lastname: Shepherd
authors.forename: Rachael T
authors.initials: RT
authors.lastname: Richardson
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000737:chemistry*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D002478:Cells, Cultured; D003054:Cochlear Implants; D004058:Diffusion; D004558:Electric Stimulation; D004566:Electrodes; D004867:Equipment Design; D005724:Ganglia / Q000166:cytology; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D011108:Polymers / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013136:Spiral Ganglion; D023822:Tissue Engineering / Q000295:instrumentation*
chemical_list: D001557:Benzenesulfonates; D019208:Brain-Derived Neurotrophic Factor; D011108:Polymers; D011758:Pyrroles; C067635:polypyrrole; C029501:4-toluenesulfonic acid