Biomaterials 24 (2003) 777–787 In vivo studies of polypyrrole/peptide coated neural probes Xinyan Cui a , James Wiler b , Marta Dzaman b , Richard A. Altschuler b , David C. Martin a,c,d, * a Macromolecular Science and Engineering Center, The University of Michigan, 2300 Hayward Street, Ann Arbor, MI 48109-2136, USA b Department of Otolaryngology, The University of Michigan, Kresge Hearing Research Institute, Ann Arbor, MI 48109-0506, USA c Department of Materials Science and Engineering, The University of Michigan, Ann Arbor, MI 48109-2136, USA d Department of Biomedical Engineering, The University of Michigan, Ann Arbor, MI 48109-2136, USA Received 4 June 2002; accepted 29 August 2002 Abstract Neural probes are micromachined multichannel electrode arrays that facilitate the functional stimulation and recording of neurons in the peripheral and central nervous system. For long-term implantations, surface modification is necessary for maintainingthestableconnectionbetweenelectrodesandneurons.Theconductivepolymerpolypyrrole(PPy)andsyntheticpeptide DCDPGYIGSR were co-deposited on the electrode surface by electrochemical polymerization. The stability of PPy/ DCDPGYIGSR coatings was tested in soaking experiments. It was found that the peptide was entrapped in the PPy film and didnotdiffuseawaywithin7weeksofsoakinginDIwater.Coatedprobeswereimplantedinguineapigbrainforperiodsof1,2and 3 weeks. Recording tests were performed and the impedance was monitored. The explanted probes and tissue were examined by immunocytochemical studies. Significantly more neurofilament positive staining was found on the coated electrode which indicated that the coatings had established strong connections with the neuronal structure in vivo. Good recordings were obtained from the coatedsitesthathadneuronsattached.Firstweektissuesectionshadnosignificantgliosis.Inweek2,alayerofnon-neuronaltissue consisting of mostly meningeal fibroblasts and ECM protein including at least fibronectin was formed around the probe tracks of both coated and uncoated probes. Astrocytes started to form a loosely organized layer by the end of the third week. r 2002 Elsevier Science Ltd. All rights reserved. Keywords: Polypyrrole; Peptides; Neural probes and Gliosis 1. Introduction Neural probes are micromachined multichannel electrodearraysthatfacilitatethefunctionalstimulation and recording of neurons in peripheral and central nervous system. One of the many challenges these devicesarefacingistheirlong-termperformanceinvivo. A current problem for chronic recording in the central nervous system (CNS) is that the devices lose the ability to record neural activity a few days to weeks after implantation. The causes of this problem may be one or more of the following: migration from the intended location after surgery, protein fouling, increase of electrode impedance, decrease of neuron density at the vicinity of the probe and isolation of the electrode sites by scar tissue formation [1–8]. Presumably, the perfor- mance of these devices could be improved by promoting better integration within the nervous system and minimizing the host response. The CNS tissue reacts to implants through a series of events. The early response to materials is primarily inflammation. The reported local degree of the reaction varies among different materials and implantation locations [9–19]. Chronically, the response is character- ized by a hypertrophic reaction from surrounding astrocytes [9,14] with elevated expression of intermedi- ate filament proteins such as GFAP and vimentin [20], the presence of a variable number of microglia and foreign body giant cells [9,10,14,16,17] and a general thickening of the surrounding tissue wrapping around the implant [2,4,14,19]. As a result, a glial-fibroblastic scar is formed and is characteristically inhibitory to *Corresponding author. Macromolecular Science and Engineering Center, The University of Michigan, 2300 Hayward Street, Ann Arbor, MI 48109-2136, USA. Tel.: +1-734-936-3161; fax: +1-734- 763-4788. E-mail address: milty@umich.edu (D.C. Martin). 0142-9612/02/$-see front matter r 2002 Elsevier Science Ltd. All rights reserved. PII:S0142-9612(02)00415-5