Neuro-Nanotechnology using Conductive Polymers Hetty Nie Neurons are notably one of the most difficult cells in the

body to heal and regenerate and therefore neurological disorders are extremely difficult to treat much less cure. The hope for new neural technologies is to improve prosthetic devices for neurological disorders ranging from deafness, to Parkinsons, and paralysis. One of the newest technologies has been to use conducting polymers to stimulate different neurological pathways in hopes that the new technology can increase the understanding of neurological diseases as well as provide innovative methods to treat these diseases. The technology is not only within research but attempts to fabricate devices that will be useful for disease treatment in the future. Conducting polymers, most notably PEDOT (Poly(3,4-ethylenedioxythiophene)) and PPY (polypyrrole) have the ability to interface with both the central and peripheral nervous system by acting as a transducer for ionic cell signals in a capacity far beyond those of classical electrodes.[1] PEDOT and PPY have become the most common choices for these technologies because of the reported low impedance and a 17% higher quality of neural recording in vivo up to approximately six weeks.[2] This effect is extremely important on the micro and nano scale since as the electrodes decrease in size, the impedance usually increases and low impedance is crucial for maintaining a high signal to noise ratio in the body which is especially critical in a noisy environment such as an organism. [3] Conductive polymers such as PEDOT and PPY are particularly attractive because they have electronic qualities similar to semiconductors while having material properties that are otherwise soft like classical polymers. The flexible material properties allow for a higher biocompatibility than electrodes made semiconductors because the more pliant material does not

stimulate an immune response as quickly as a hard material such as a semiconductor. Therefore, the polymer covered electrodes will take longer to be identified as foreign material and covered in astrocytes and will produce a more readable signal for longer.[3] Additionally, electrochemically polymerized conductive polymers can be fabricated into many different morphologies such as films, interconnected cavities, microfibrils and nanotubes which increase the usable surface area on electrodes. However, nanotubes are the most common since they have been shown to have higher sensitivity and need fewer molecules for detection than the other morphologies.[1] Polymer nanotubes are fabricated on top of the electrode in a process known as electrochemical polymerization, shown figure 1.[1] First, nanofibers made in of

biocompatible polymers such as poly(lacticco-glycolic acid) (PLGA) or poly(L-lactic acid) (PLLA) that contain an encapsilated drug such as dexamethasone (DEX) are deposited onto an electrode by

electrospinning (a to b). Then, the electrode and fibers are encapsulated in an alginate hydrogel which is then connected to an external electric current stimulates the growth of the PEDOT or PPY around the PLGA fibers. Later the PLGA or PLLA is removed
Figure 1. Schematic of the fabrication process for developing polymer coatings on neural microelectrodes.

to create interconnected tube like structures. Characterization of the resulting fibers were performed through SEM and the characterization of the conductivity of the polymer was performed using Electrochemical Impedance Spectroscopy (EIS). [1] These nanotube covered electrodes have been studied in vivo with animal trials to

observe both short and long term immune responsnes against the electrodes. The study that was conducted implanted standard probes into three rats and compared the recordings of impedance and signal to noise ratio to control. The study concluded that impedance was much lower than classical electrode although both showed similar trends of increasing in impedance the longer the electrode was implanted, and although both the signal and noise increased for both electrodes over the timespan of two weeks, the nanotube coated electrode performed from .8% better than the conventional electrode (immediately after surgery) to 3.7% better (about two weeks after the initial surgery.)[4] Besides being a biosensor by being a cell transducer, PEDOT nanobased electrodes have been suggested for the sensing of glucose. However, the fabrication of the electrode requires a slightly different approach using entrapped enzymes in PLGA or PLLA on platinum electrodes. The technique is useful since it bypasses the harsh chemicals that is required by most other techniques using enzymes.[5] Nanotube conducting polymer electrodes are not only being suggested biosensing, but are also suggested for applications in drug delivery. Because of the electrical properties of the conductive polymers, the nanotubes can be compelled to expand and contract by manipulating the external voltages. The fabrication of an electrode for drug delivery is very similar to that for biosensing. PEDOT nanotubes are grown around PLGA or PLLA nanowires containing a drug. The drug will have difficulty escaping from the nanotube since it has such a high aspect ratio and

the PLGA or PLLA will further retard the escape of the drug. When an external voltage is applied, the nanotube will dilate and allow more of the drug to escape and thereby control the drug release.[1] To further increase the electrical sensitivity of the nanotubes to more easily control the drug release profiles, it has been suggested to blend the conducting polymer nanotubes with single walled carbon nanotubes (SWNTs). The carbon nanotubes act as a scaffold for the PEDOT to polymerize and results in a surface morphology that is distinct from both PEDOT and SWNTs alone shown by Figure 2 below.[6]

Figure 2. SEM images of the morphologies of SWNT-PEDOT coating, SWNTs coating alone, and PEDOT coating alone, respectively.

Even further, PEDOT has been used with electrically active tissues in the body such as neurons, cardiac and skeletal muscles. In an in vitro study, cultured neurons were subjected to EDOT (PEDOT monomer). The PEDOT nanotubes were then polymerized around the living cells. The cells were viable for up to 72 hours with 80% cell survival when subjected to EDOT and were generally easily separable from the PEDOT scaffold and were viable for nearly five days after PEDOT polymerization.[7] In a different study, PEDOT nanotube scaffolds were used to stimulate the growth of electrically active cells because the PEDOT propagated electrical signals where the cells have been damaged. Not only did the PEDOT encourage cell growth

because of the electrical properties, it also acted as a scaffold for new cells to branch and grow as shown in Figure 3. [8]

Figure 3 Confocal microscopy images of stained neuroblastoma cells growing on a PEDOT coated surface (a) and a glass treated for cell culture purposes (b) respectively.

Conductive polymers show a new hope in furthering the methods for treating neurological diseases. They offer a new and more biocompatible material with which to create electrode interfaces, in addition to having applications as a new strategy for biosensing. But most of all, conductive polymers have indications for neuron regeneration which may be the key to curing many neurological ailments from sensory disorders to paralysis to Parkinsons. Nanoscale PEDOT and other conductive polymers provide increasingly promising solutions to many neurological diseases that currently have very few treatment options.

References [1]M. R. Abidian, D.C. Martin. Multifunctional Nanobiomaterials for Neural Interfaces. Volume 19, Advanced Functional Materials, pp 573-585, 2009 [2] M. R. Abidian, K. A. Ludwig, T. C Marzullo, D. C. Martin, D. R. Kipke. Interfacing Conducting Polymer Nanotubes with Central Nervous System: Chronic Neural Recording using Poly(3,40ethylenedioxythiophene) Nanotubes. Volume 21, Advance Materials, pp 3764-3770, 2009. [3] M.R. Abidian, J. M Corey, D.R. Kipke, D. C. Martin. Conducting-Polymer Nanotubes Improve Electrical Properties, Mechanical Adhesion, Neural Attachment, and Neurite Outgrowth of Neural Electrodes. Volume 3, Small, pp 421-429, 2010. [4] M. R. Abidian, L. G. Salas, A. Yazdan-Shahmorad, T. C. Marzullo, D. C. Martin, D. R. Kipke. In-Vivo Evaluation of Chronically Implanted Neural Microelectrode Arrays Modified with Poly (3,4-ethylenedioxythiophene) Nanotubes. Proceedings of the 3rd International IEEE EMBS Conference on Neural Engineering. May2-5, 2007. [5] K. N. Layton and M. R. Abidian. Conducting Polymer Nanofiber-Based Biosensor for Detection of Neurochemicals. Proceedings of the 5th International IEEE EMBS Conference on Neural Engineering. April 27- May 1, 2011. [6] Y. Xiao, X. Ye, L. He, J. Che. New Carbon Nanotube-Conducting Polymer Composite Electrodes for Drug Delivery Applicatioins. Volume 61, Polymer International, pp 190-196, 2011. [7] S. M. Richardson-Burns, J. L Hendricks, B. Foster, L. K. Povlich, D. H. Kim, D. C Martin. Polymerization of the Conducing Polymer Poly(3,4-ethylenedioxytiophene) (PEDOT) Around Living Neural Cells. Volume 28, Biomaterials, pp 1539-1553, 2006. [8] M. H. Bolin, K. Svennerson, X. Wang, I. S. Chronakis, A. Richter-Dahlfors, E. W. H. Jager, M. Berggren. Nano-fiber Scaffold Electrodes Based on PEDOT for Cell Stimulation Volume 142, Sensors and Actuators, pp451-456, 2009.