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CONDUCTING POLYMERS: A BRIDGE ACROSS THE BIONIC INTERFACE

By Wallace, Gordon G,Spinks, Geoffrey M
Publication: Chemical Engineering Progress
Date: Saturday, December 1 2007
HEADNOTE

Inherently conducting polymers (ICPs) exhibit a variety of dynamic behaviors that make them an exciting platform for a new generation of bionic devices.

Bionics - the quest to interface the worlds of biology and electronics to improve human performance

- is a fascinating and challenging field of research. One of the most successful bionic devices developed to date is the cochlear implant (1), wherein nerve cells located in the cochlea are reconnected to the world of sound using a 22electrode array, a speech processor and a microphone system. Other bionic devices include the bionic eye (2), stimulators for restoration of function in damaged spinal cord (3) and a neuroprosthesis for restoration of hand control (4).

Existing bionic devices use conventional electronic materials that are often not inherently compatible with biological systems. Although implant materials that are biocompatible (i.e., the biochemical and cellular changes they undergo in vivo are not harmful) do exist, the hard and static nature of metals and metal oxides are quite foreign to the biological environment.

Inherently conducting polymers (ICPs) are much more similar, in terms of general properties, to biological macromolecular structures. ICPs have mechanical behaviors similar to biological tissue, so they can function as an implant in a less obtrusive manner. Of course, the ability to conduct electrical charge into and out of cells makes these materials attractive alternatives to conventional, hard electronic materials.

However, what really makes ICPs exciting for biological applications is their dynamic nature. That, coupled with their soft character, provides an extra dimension in designing interfaces between the hard, digital electronics world and the soft, amorphous world of biological systems.

In this article, we introduce the dynamic behavior of ICPs and show examples of how these materials might be used in either wearable or implantable bionics.

Dynamic behavior of ICPs

Inherently conducting polymers, such as polypyrroles, polythiophenes and polyanilines (Figure 1), have become widely studied in today's materials research laboratories. While their conductivity is typically in the semi-conductor range (0.1-1,000 S/cm), the most intriguing aspect of these materials is their ability to control their physical and chemical properties.

For example, the relatively simple redox chemistry depicted in Eq. 1 (Figure 2) forms the basis of polypyrrole's dynamic behavior and its ability to function at the bionic interface. The facile redox chemistry elicits significant changes in a wide range of properties: the conductivity can change by ten orders of magnitude; the polymer's color changes; the polymer can switch from hydrophilic to hydrophobic; permeability to chemical species changes; the volume changes; and the mechanical properties (e.g., Young's modulus) change. All of these property changes occur upon the application of small voltages (typically less than 1 V) when the ICP is in contact with an electrolyte medium and connected to an auxiliary electrode (which can also be an ICP).

As synthesized, via oxidation of the monomers, ICPs are present in the charged conducting form. The positive charge on the polymer backbone is counter-balanced by a dopant (A~). This dopant can be a simple anion such as chloride, in which case, for thin uniform films of the material, the reaction shown in Eq. 1 would hold true. That is, for a PPy/Cl film, reduction of the material would result in chloride ion expulsion. Assuming this reaction was carried out in chloride-containing media, then reoxidation would result in chloride ion incorporation. However, where A~ is a large anionic species, the dopant anion is immobile. The charge balance in such cases is, therefore, maintained by incorporation of a cation from the electrolyte media in which the reduction occurs (Eq. 2). Many practical applications use this ability of the ICP to controllably expel or imbibe charged molecules.

A particular advantage of ICPs is the ability to tailor their structure and properties through the choice of the dopant species. The dopant can constitute over 50% wt. of the polymer, so its influence on properties will be significant. Several ICPs have been formulated using biological polyelectrolyte dopants, such as heparin or hyaluronic acid - producing electronic conductors that are organic in nature with a significant portion of the conducting polymer (the dopant) being a biological entity. The ability to functionalize the polymer using various biological molecules provides the potential for specifically targeting the action of the ICPs in controlled ways.

Wearable bionic devices

An ICP-coated Lycra material is an excellent wearable strain gage (5) capable of monitoring human movement. A resistance change occurs when the fabric is stretched, since the number of connections between individual conducting fibers changes as the fabric strains. A reasonably linear response has been reported over a wide deformation range. This large dynamic range in a non-encumbering, comfortable device means that the system is ideally suited for studying and monitoring complex human movements (6, 7).

This approach is the basis for a bio-feedback device for training athletes (7) (Figure 3). The sleeve was used to teach Australian Football League players how to land properly after jumping (8), so that the incidence of debilitating injuries due to rupture or tearing of knee ligaments could be reduced. This device was first tested by the Geelong Football club in 2004 with the assistance of Dr. Hugh Seward.

Bending deformation sensors with ICPs operating in an electrochemical environment have also been recently developed (9). These multilayer structures combine two outer ICP films sandwiched on either side of a porous membrane that holds a low-volatility electrolyte. Bending causes one ICP layer to stretch and the other to compress. These strains produce small changes in the osmotic pressure equilibrium that is established between the ICP and the electrolyte such that dopant ions will move between the electrolyte and the ICP in response to the applied strain. A mechanical sensor then measures the potential difference (or charge transferred) between the ICP layers. Here, too, the flexible, lowprofile nature of these devices makes them suitable for use in human movement studies. While these bending deformation sensors have a more-complex structure than the ICPcoated stretchable fabrics, they are more sensitive to small deformations and can be easily miniaturized.

Electrochemical movement sensors can also operate in reverse. In fact, they were first constructed as electromechanical bending actuators (10,11). When a voltage is applied between the ICP layers, oxidation/reduction reactions occur that lead to the incorporation and expulsion of ions, which, in turn, results in a significant reduction/expansion in volume. Configured appropriately, this oxidation/reduction can cause significant movement as one side of a laminated membrane expands while the other contracts. With the use of appropriate dopants and electrolytes, very fast actuation can be obtained (12) (Figure 4).

Can these actuator devices operate as "artificial muscles" to produce human movement and even develop the superhuman abilities of Steve Austin, the "bionic man" on the TV series The Six-Million Dollar Manl Manipulating human movement is, of course, a mammoth task. In today's highly technological world, we still do not have adequate lightweight, low-powerconsumption materials or technologies that can be strapped on to assist in human movement (50). However, when the performance of natural muscle is compared with conventional mechanical drive systems (motors, pneumatics, hydraulics), the sophistication of muscle as a machine can be appreciated. While these conventional drive systems outperform muscle at the macro-scale, muscle clearly wins at the micro and sub-micro scale. Humanoid robots like Honda's ASIMO show very impressive locomotion skills, but they currently lack dexterity. Even producing the myriad facial expressions to express emotion is an extremely complex task, involving the coordinated action of dozens of individual actuators packed into a very small volume (13). To truly emulate human agility, small, lightweight and low-power actuators are needed.

The pursuit of artificial muscles based on ICPs was initiated by Baughman (14). There have since been numerous demonstrations of bending (15) and linear (16) actuators covering the macro-scale (17) to the microscopic (18). These actuators operate electrochemically as shown in Eqs. 1 and 2, with the polymer expanding and contracting as a result of the ion flux into and out of the polymer. Numerous applications have been proposed or demonstrated including in robotics (19), micro-machines (18), an electronic Braille screen (20) and bionic devices such as a "rehabilitation glove" (21).

While significant improvement in the performance of artificial muscle based on conducting polymers has occurred in recent years, there is still some way to go before bionics can match natural muscle in terms of speed, efficiency and control. The largest reported strain is currently around 40% (22), although this takes several minutes to occur and decays quickly on repeated cycling. The speed of response has been increased by improving the electrochemical control (23) and the conductivity of the structure used (20). The fastest response from an ICP actuator (15%/s) is, however, still considerably slower than natural skeletal muscle (~80%/s). Next to large movements, speed is critically important in generating useful motion. The large, fast movements possible through musculoskeletal systems in animals is the basis of running, flying, swimming - attributes that would be highly desirable in nimble, dexterous and possibly miniaturized robots.

Recent developments in materials are moving closer to these possibilities. Carbon nanotubes (CNTs), for example, have proven very useful as actuators, both on their own and as the reinforcing phase in composite materials. Like natural muscle, the formation of CNTs and ICPs into fibers provides a better geometry for actuator performance. CNT fibers (24-26) and polyaniline fibers (27) are now readily available with high strength and conductivity. The addition of small quantities of CNTs to polyaniline, followed by wetspinning and drawing, produces superior actuation response under an external load (28). In fact, an actuation response was measured at more than 100 MPa applied stress, which is three times higher than previously reported for conducting polymer actuators.

The response of actuators under load has also been improved by using ionic liquids as electrolytes (29). Ionic liquids also vastly improve the operating lifetime of conducting polymer actuators (and other devices) through the elimination of side reactions (30).

The choice of electrolyte dramatically improves the performance of polypyrrole actuators in terms of strain produced and speed of response. Very large strains can be achieved by using particular dopants and electrolytes (22), and the same system in bending mode can be used to generate very fast movements (12) (Figure 4). Accurate control of these movements is the subject of recent work (31).

Clearly, there is still some way to go before artificial muscles can match the performance of the natural systems. However, given the current rate of progress, the use of artificial muscles in bionic applications may not be far away. In fact, the "arm wrestling" challenge using prosthetic arms powered by artificial muscles is now an annual event (32).

No doubt patients suffering paralysis, tremors, arthritis or other movement disorders are eager for us to win the challenge -where an artificial-muscle-powered arm wrestles a human, and wins!

Implantable bionic devices

Although applications external to me body may be easier to develop initially, it is the ability of ICPs to interact with living tissue and cells that holds the most exciting prospects for future bionic applications. Can the sensing, actuating, controlled-release and energy-storage abilities of ICPs be developed to replace or augment natural body functions?

Rapid progress is being made in several areas, driven by the increasing understanding of how ICPs operate and by the advent of new materials, especially nano-materials and nanocomposites. Electronic communication with living cells is of interest, wim a view to improving the performance of implants for tissue engineering or bone regrowth (33). It is also critical to the performance of implants such as the bionic ear (1) or bionic eye (34), and may be further harnessed for targeted drug delivery and implanted biosensors.

Cell scaffolds

One powerful therapeutic technology is the controlled growth of human cells: there is a need for stem cells, nerve cells and muscle cells to be cultured, located and connected to surrounding tissues. The dynamic nature of ICPs makes them attractive as cell scaffolds.

Cell attachment and growth are affected by many factors, including surface chemistry and topography and even the hardness of the material. ICPs can be formulated to tune all of these factors. For example, the wettability of conducting polymers is significantly influenced by the application of electrical stimulation (Figure 5). At the mechanical level the elastic modulus of polypyrrole has been shown to change by a factor of four during redox cycling (35), and the dynamic cycling of surface stiffness may be useful in encouraging and directing cell growth (36-38).

While these fascinating properties can be used to influence cell behavior, the polymer composition determines polymercell compatibility. Obviously, intimate polymer-cell contact is required if effective electronic/molecular communication is to occur. For example, PPy containing heparin (a biological polyelectrolyte) as the dopant has been used to support endothelial cell growth (39, 40). With this dopant, the cells spread toform a confluent layer and adopt a morphology typical of healthy cells. The presence of the heparin as an integral part of the conducting structure was critical, as the use of other non biological dopants was not successful. More recently, the use of carboxy-endcapped polypyrroles has been shown to improve adhesion of endothelial cells (41).

Material composition is also critical in the growth of nerve cells on conducting polymers. In early work, the use of polyelectrolyte dopants (both biological (42) and synthetic (43)) was useful. The polyelectrolyte dopant results in formation of an electronic (soft) hydrogel still capable of delivering electrical stimulation.

PPy doped with conventional dopants, such as dodecylbenzenesulfonate (44) and poly(styrenesulfonate) (45) ions, has proven successful in neurite studies. The use of biologically significant dopants considerably improves neurite attachment and extension. For example, when a protein polymer containing fibronectin fragments and a nonapeptide were used as the PPy dopant, the cellular response was better than that of CH^sub 3^COO-doped PPy (46).

Neurite extension of PC-12 cells was more pronounced on PPy surfaces than on polystyrene (42, 47). The application of an electrical stimulus significantly increased the expression of neurites in the cells by providing a release mechanism for a nerve growth factor from the ICP platform (43). Stimulation also increases the adsorption of fibronectin, and this plays a critical role in promoting neurite extension (48).

In a study of polypyrrole implants for neural prosthetics (44), PPy doped with poly(styrenesulfonate) or dodecylbenzenesulfonate was implanted into a rat's cerebral cortex, and was shown to perform as well as (or better than) Teflon. Neurons and glial (central nervous system) cells enveloped the implant, providing a direct electrical route to brain cells via the implants. Such implants may provide a route for the transmission of external and internal electronic signals to brain tissue post-operatively to simulate and/or repair damaged neural structures.

Nerve axons can grow on a PPy surface, and the development of axons can be influenced by controlled release of nerve growth factors incorporated in the polymer to stimulate axon formation (49). In addition, PPy-coated electrodes can effectively transduce an a.c.-modulated electrical stimulus to neural tissues via in vivo recording. The biocompatibility of PPy, therefore, makes it an exciting substrate for neural scaffold structures, nerve stimulation by charge injection, and implant devices.

While direct electrical stimulation obviously has a beneficial effect, it is again the multidimensional effects arising from electrical stimulation of ICPs that provide unique possibilities. We have demonstrated the cumulative beneficial effect of direct electrical stimulation and localized controlled (on demand) release of growth factors such as neurotrophin-3 (NT3) in promoting the outgrowth of neurites from an explant containing dorsal root ganglion cells. Explants were grown for 24 h on PPy coated with cell adhesion molecules (CAM) and doped with p-toluene sulfonate, both with neurotrophin-3 (PPy/pTS/NT3) and without (PPy/pTS), and these explants were subjected to a Diphasic current-pulse stimulus for 1 h. Neurite outgrowth was examined after three days in culture. The explants grown on the stimulated PPy/pTS/NT3 had more neurites per explant (Figure 6a) than the explants grown on stimulated PPy/pTS (Figure 6b). Stimulation of PPy/pTS did not significantly alter the number of neurites per explant compared to unstimulated PPy/pTS (p = 1.0). On the other hand, explants grown on PPy/pTS/NT3 with applied stimulation experienced enhanced neurite outgrowth compared to explants grown on unstimulated PPy/pTS/NT3 and compared to stimulated or unstimulated PPy/pTS (p < 0.001).

Closing thoughts - get ready for nanobionics! .

The continuing advances in nanotechnology related to ICPs discussed here are taking us closer to realizing the true potential of these materials in the field of medical bionics.

More-effective bridging of the bionic interface will impact greatly on many aspects of medical science. For example, more-efficient connectors to nerve cells will immediately enhance the performance of implants such as the bionic ear and the bionic eye. Efficient stimulation of oesteoblasts will assist in bone regrowth, while the promotion of endothelial cell growth is critical in wound healing as well as in the integration of implants such as stents. Further development of artificial muscle technology based on ICPs will also have a dramatic impact on those requiring assistance with movement either during rehabilitation or due to disease or injury.

As material scientists and engineers delve into the nanodomain, particularly with ICPs, the boundaries between electronics and biology become fuzzy. This is exactly what we want - a seamless transition between the hard world of electronics and the soft world of biology!

The field of nanobionics offers the exciting prospect of applying the many new nano-structured materials in combination with dynamically tunable materials like ICPs to herald a new age of manipulation and control of the biological world.

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AUTHOR_AFFILIATION

GORDON G. WALLACE

GEOFFREY M. SPINKS

INTELLIGENT POLYMER

RESEARCH INSTITUTE

UNIV. OF WOLLONGONG

AUTHOR_AFFILIATION

GORDON G. WALLACE is executive research director of the ARC Centre of Excellence for Electromaterials Science, which is part of the Intelligent Polymer Research Institute at the Univ. of Wollongong (Northfields Ave., Wollongong, NSW 2522, Australia; Phone: +61-2-4221-3127; Fax: +61-2-4221-3114; E-mail: gwallace@uow.edu.au). His research interests include organic conductors, nanomaterials and electrochemical probe methods of analysis. A current focus involves the use of these tools and materials in developing biocommunications from the molecular to skeletal domains in order to improve human performance via medical bionics. Wallace has authored more than 400 refereed publications and a monograph (two editions) on inherently conducting polymers for intelligent material systems. He has supervised 50 PhD students to the completion of their degree. He is a fanatical supporter of the Geelong Football club, which tested the knee sleeve shown in Figure 3 and recently won the 2007 Australian Football League premiership.

GEOFFREY M. SPINKS is a professor of materials engineering at the Univ. of Wollongong (Phone: +61-2-4221-3010; E-mail: gspinks@uow.edu.au). He holds a Bachelor of Applied Science and a PhD in polymer science from the Univ. of Melbourne. Since joining the Univ. of Wollongong in 1990, he has developed a research program in electroactive polymers, especially for artificial muscles and sensors, and has published more than 100 refereed journal articles. He is not a fan of the Geelong Football club.

Acknowledgements

Many colleagues and PhD students have made significant contributions to this area of research - thank you! We are also indebted to the Australian Research Council (ARC) for its continuing financial support.