Electrically Conductive Biodegradable Polymer Composite for Nerve Regeneration: Electricity-Stimulated Neurite Outgrowth and Axon Regeneration *†Ze Zhang, ‡Mahmoud Rouabhia, †§Zhaoxu Wang, ¶Christophe Roberge, †§Guixin Shi, ¶Phillippe Roche, ¶Jiangming Li, and ¶Lê H. Dao *Département de chirurgie, Faculté de médecine, Université Laval; †Centre de recherche, Hôpital Saint-François d’Assise, CHUQ; ‡Faculté de médecine dentaire, Université Laval; §Médecine expérimentale, Faculté de médecine, Université Laval, Québec; and ¶Laboratoire de matériaux avancés, INRS-EMT, Université du Québec,Varennes, Québec, Canada Abstract: Normal and electrically stimulated PC12 cell cul- tures and the implantation of nerve guidance channels were performed to evaluate newly developed electrically conductive biodegradable polymer composites. Polypyr- role (PPy) doped by butane sulfonic acid showed a signifi- cantly higher number of viable cells compared with PPy doped by polystyrenesulfonate after a 6-day culture. The PC12 cells were left to proliferate for 6 days, and the PPy- coated membranes, showing less initial cell adherence, recorded the same proliferation rate as did the noncoated membranes. Direct current electricity at various intensities was applied to the PC12 cell-cultured conductive membranes. After 7 days, the greatest number of neurites appeared on the membranes with a current intensity approximating 1.7–8.4 mA/cm. Nerve guidance channels made of conductive biodegradable composite were implanted into rats to replace 8 mm of sciatic nerve. The implants were harvested after 2 months and analyzed with immunohistochemistry and transmission electron microscopy. The regenerated nerve tissue displayed myeli- nated axons and Schwann cells that were similar to those in the native nerve. Electrical stimulation applied through the electrically conductive biodegradable polymers therefore enhanced neurite outgrowth in a current-dependent fashion. The conductive polymers also supported sciatic nerve regeneration in rats. Key Words: Conductive polymer—Polypyrrole—Biodegradable polymer—PC12— Electrical stimulation—Neurite—Nerve guidance channel. Nerve injuries are among the primary causes of human disability, including lost mobility and sensory function. Transected nerves can be bridged using nerve grafts. Current medical practice uses autografts taken from other parts of the patient’s body. Unfor- tunately, this causes additional scarring and pain, as well as permanent sensory function loss of the donat- ing location (1). The synthetic nerve guidance channel therefore provides surgeons with an interest- ing option to bridge severed nerves. Among the various materials, synthetic biodegradable polymers such as poly(l-lactide) (2), poly(D, l-lactic-co- glycolic acid) (3), and the more flexible poly (D, l-lactide-epsilon-caprolactone) (4–6) have been widely tested. More recently, the focus has been on the incorporation of Schwann cells (7,8) and neu- rotrophic factors (9,10) into nerve guidance channels. Electrical stimulation is an effective cue to enhance neurite and axonal outgrowth (11–14) and consequently makes the use of electrically conduc- tive polymers very attractive in the construction of nerve guidance channels. Polypyrrole (PPy), an inher- ently conductive polymer, is shown to support neu- ronal growth, as the electrical stimulation applied through the PPy membrane enhances neurite out- growth (15). However, due to its highly conjugated molecular backbone, PPy is brittle, rigid, and nonbio- degradable, and is therefore difficult to use alone to make a nerve guidance tube. We recently developed a novel electrically conduc- tive biodegradable composite based on PPy and poly(D, l-lactide-co-epsilon-caprolactone) (PDLLA/ doi:10.1111/j.1525-1594.2007.00335.x Received February 2006; revised June 2006. Address correspondence and reprint requests to Dr. Ze Zhang, Hôpital Saint-François d’Assise, 10 rue de l’Espinay, local E0-165, Québec (QC), Canada, G1L 3L5. E-mail: Ze.Zhang@chg.ulaval.ca Artificial Organs 31(1):13–22, Blackwell Publishing, Inc. © 2007, Copyright the Authors Journal compilation © 2007, International Center for Artificial Organs and Transplantation 13