Effect of the dopant anion in polypyrrole on nerve growth and release of a neurotrophic protein Brianna C. Thompson a , Simon E. Moulton a , Rachael T. Richardson b , Gordon G. Wallace a, * a ARC Centre of Excellence for Electromaterials Science, Intelligent Polymer Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia b The Bionic Ear Institute, 384 Albert Street, East Melbourne, Victoria, Australia article info Article history: Received 6 December 2010 Accepted 4 January 2011 Available online 25 February 2011 Keywords: Polypyrrole Neurotrophin-3 Dopant Electrical stimulation Neural abstract The dopant anion in polypyrrole plays a critical role in determining the physical and chemical properties of these conducting polymers. Here we demonstrate an additional effect on the ability to incorporate and release a neurotrophic protein e neurotrophin-3. The multi-faceted role of the dopant is critical in ensuring optimal performance of polypyrroles in their use as platforms for nerve growth. In this paper, the effect of changing the co-dopant used in electrochemical polypyrrole synthesis on the compatibility with primary auditory nerve tissue is considered and compared to some of the physical properties of the films. Significant differences in the controlled-release properties of the films were also observed. The ability of the polymers to enhance nerve growth and survival in vitro with neurotrophin-3 release was also studied, which is a function of both compatibility with the neural tissue and the ability of the polymer to release sufficient neurotrophic protein to affect cell growth. A small synthetic dopant, para- toluene sulphonate, was found to perform favourably in both aspects and ultimately proved to be the most suitable material for the application at hand, which is the delivery of neurotrophins for inner-ear therapies. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction Sensorineural hearing loss is the most common form of hearing loss and involves the loss of sensory hair cells. In severe cases, cochlear implantation is the only option available to restore hearing. However, the loss of hair cells leads to progressive degeneration of auditory neurons (spiral ganglion neurons) and eventual apoptosis of these cells [1,2]. The loss of these spiral ganglion neurons can have detrimental affects on the functioning of the cochlear implant, due to a decrease in the integrity of the nerveeelectrode interface [3]. Strategies to prevent the degeneration of the auditory nerve are therefore of interest to improve the function of the cochlear implant. The application of neurotrophins to the cochlea as a means of promoting survival of spiral ganglion neurons has been investi- gated over several years. Various neurotrophins, including neuro- trophin-3 (NT-3), have been applied to cultured neurons and to the cochlea in vivo (for a review of potential clinical applications of neurotrophins in inner-ear therapies, see [4]). Both NT-3 and another neurotrophin, brain-derived neurotrophic factor (BDNF), have been shown to enhance nerve survival when applied either immediately post-deafening [5e7], or after partial neural degen- eration has occurred post-deafening [8,9]. Two major challenges remain for therapeutic use of the neurotrophins in the deafened cochlea. Firstly, a safe method is required to deliver the therapeutic proteins into the cochlea that minimises the risk of infection and does not disrupt the function of the cochlear implant, and secondly, the neurotrophins must be delivered for an extended period of time for the rescued nerves to become established. Polypyrrole (PPy) has potential to act as a controlled-release material to provide neuro- trophin delivery without disrupting the cochlear implant function, as it could coat the existing platinum electrodes without increasing the impedance, adding additional surgical steps, or introducing additional devices into the ear. The use of PPy as a matrix for storage and electrically-controlled delivery of drugs has been investigated for several molecules [10e18]. The authors have previously reported the controlled delivery of nerve growth factors, in particular NT-3 [19,20] and brain-derived neurotrophic factor [21,22]. An important consider- ation in use for the controlled release of molecules is the dopant used during the electrochemical synthesis of PPy films. While often the dopant is the drug or molecule of interest, some systems use a co-dopant to reduce the amount of drug used, or to improve the electrical, mechanical or other physical properties of the polymer [10,11,14,19e24]. * Corresponding author. Tel.: þ61 2 4221 3127; fax: þ61 2 4221 3114. E-mail address: gwallace@uow.edu.au (G.G. Wallace). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2011.01.053 Biomaterials 32 (2011) 3822e3831