A Conducting-Polymer Platform with Biodegradable Fibers for Stimulation and Guidance of Axonal Growth By Anita F. Quigley, Joselito M. Razal, Brianna C. Thompson, Simon E. Moulton, Magdalena Kita, Elizabeth L. Kennedy, Graeme M. Clark, Gordon G. Wallace,* and Robert M. I. Kapsa Effective functional innervation of medical bionic devices, as well as reinnervation of target tissue in nerve and spinal-cord injury, requires a platform that can stimulate orientated neural growth. Conducting and non-conducting biodegradable polymers have shown potential as suitable substrata for remodeling neural tissues. While these polymers are often evaluated individually, hybrid systems may offer some advantage. This report describes a biosynthetic platform, developed to direct nerve regeneration composed of a conducting polypyrrole (PPy) sheet overlaid with unidirectional, biodegradable polymer fibers. Dorsal root ganglia (DRG) explants, grown on these platforms, demonstrate axonal and Schwann cell alignment with the fibers. In addition, enhanced neurite outgrowth and Schwann cell migration was achieved after direct electrical stimulation via the conductive- polymer layer. We propose that such hybrid systems can promote rapid, directional nerve growth for the engineering of neu- ro-regenerative scaffolds and as interfaces between the electronic circuitry of medical bionic devices and the nervous system. Material platforms that can stimulate and spatially direct nerve growth hold great potential for the restoration of damaged or otherwise dysfunctional tissue and organ systems. In particular, such materials offer significant potential benefits for the functional reconnection of damaged nerves in the peripheral and central nervous systems (e.g., spinal cord) and for a connection of the neural circuitry to electronic bionic devices. The fabrication of polymer scaffolds for tissue engineering requires controlled synthesis that accommodates the structural and functional requirements of the target tissue. The major functional requirement for neural scaffolds is bridging of the injured neural tissue to re-establish effective neurotransmission by promotion of appropriate axonal outgrowth and innervation of tissues. Likewise, connection of implantable bionic devices with the nervous system requires stimulation and direction of functional nerve growth to the appropriate electronic circuitry that controls the device. From a structural standpoint, neural scaffolds for regenerative and bionic applications alike, therefore, need to incorporate a configuration that provides regenerative axonal stimulation, structural support, and appropriate guidance cues to regenerate axons as well as to supporte neuro-glial ensheathing cells. Within this context, organic conducting polymers (OCPs) provide advantages through their ability to conduct electrical signals to influence cell behavior or transmit signals between neural and electronic circuitry. PPy is a biocompatible OCP that has been used for the stimulation of neural growth and regeneration both in vivo and in vitro. [1–3] Electrical stimulation via PPy has been shown to directly enhance neurite outgrowth in PC12 (neural) cell lines, [2–4] and to positively influence neuronal outgrowth in primary spiral ganglion explants by controlled release of neurotrophins. [5,6] Likewise, a number of (non-conducting) biodegradable polymer formulations have shown potential to support neuro- regenerative activity in peripheral nerve [7–9] and spinal cord. [10] In particular, micropatterned poly-D,L-lactic acid (PLA) and poly(lactide-co-glycolide) (PLGA) polymers coated with the cell-adhesion molecule (CAM) laminin, were shown to direct neural outgrowth from DRG, achieving up to 95% alignment of neurites through both physical (micropatterned surface) and biochemical (laminin) guidance cues. [11] In addition, a previous study by Corey et al [12] has shown that nanostructures generated by electrospun poly-L-lactate nanofibers were able to influence directional neurite outgrowth from DRG; however, these experiments did not involve the electrical stimulation aspects described here. Biodegradable polymers have the advantage of being easily manipulated and provide excellent temporary scaffolds for tissue regeneration that can be tuned to degrade and liberate space for regenerating or infiltrating nerve tissue. To date, the development of OCPs and biodegradable polymer formulations for neural cell growth and differentiation has largely been carried out utilizing individual polymer components. COMMUNICATION www.advmat.de [*] Prof. G. G. Wallace, Dr. A. F. Quigley, Dr. J. M. Razal, B. C. Thompson, Dr. S. E. Moulton, M. Kita, Prof. G. M. Clark, Prof. R. M. I. Kapsa ARC Centre of Excellence for Electromaterials Science Intelligent Polymer Research Institute University of Wollongong Northfields Avenue Wollongong, NSW 2522 (Australia) E-mail: gwallace@uow.edu.au Dr. A. F. Quigley, M. Kita, Prof. G. M. Clark, Prof. R. M. I. Kapsa Centre for Clinical Neuroscience and Neurology Research Department of Medicine, St. Vincent’s Hospital 41 Victoria Pde Fitzroy, VIC 3065 (Australia) Dr. A. F. Quigley, M. Kita, E. Kennedy, Prof. G. M. Clark, Prof. R. M. I. Kapsa Bionic Ear Institute 384-388 Albert St East Melbourne, VIC 3002 (Australia) DOI: 10.1002/adma.200901165 Adv. Mater. 2009, 21, 1–5 ß 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 1 Final page numbers not assigned