Publications
113 results found
Poole-Warren L, Martens P, Green R, 2015, Biosynthetic Polymers for Medical Applications, ISBN: 9781782421139
© 2016 Elsevier Ltd. All rights reserved. Biosynthetic Polymers for Medical Applications provides the latest information on biopolymers, the polymers that have been produced from living organisms and are biodegradable in nature. These advanced materials are becoming increasingly important for medical applications due to their favorable properties, such as degradability and biocompatibility. This important book provides readers with a thorough review of the fundamentals of biosynthetic polymers and their applications. Part One covers the fundamentals of biosynthetic polymers for medical applications, while Part Two explores biosynthetic polymer coatings and surface modification. Subsequent sections discuss biosynthetic polymers for tissue engineering applications and how to conduct polymers for medical applications. Comprehensively covers all major medical applications of biosynthetic polymers. Provides an overview of non-degradable and biodegradable biosynthetic polymers and their medical uses. Presents a specific focus on coatings and surface modifications, biosynthetic hydrogels, particulate systems for gene and drug delivery, and conjugated conducting polymers.
Green RA, Goding JA, 2015, Biosynthetic conductive polymer composites for tissue-engineering biomedical devices, Biosynthetic Polymers for Medical Applications, Editors: Poole-Warren, Martens, Green, Publisher: Elsevier, Pages: 277-298, ISBN: 9781782421054
© 2016 Elsevier Ltd. All rights reserved. Conductive composites based on conductive polymers (CPs) have enabled the development of a range of materials for biomedical applications that can be tailored to improve material properties critical to long-term performance of implantable devices. Nonconductive polymers can be used to impart tailored presentation of biomolecules and improve the brittle mechanical properties of CPs. Additionally, CPs have been used to successfully impart conductivity to hydrogel and elastomeric polymers. While there have been significant challenges in producing interpenetrating networks of CPs, several approaches have yielded materials with bulk characteristics that indicate the presence of each of the component polymers. True interpenetrating networks (IPNs), such as double networks, where one network is a CP have not yet been realised; however, it is expected that IPNs will provide optimal materials with the highest electroactivity.
Aregueta-Robles UA, Lim KS, Martens PJ, et al., 2015, Producing 3D neuronal networks in hydrogels for living bionic device interfaces, Pages: 2600-2603, ISSN: 1557-170X
© 2015 IEEE. Hydrogels hold significant promise for supporting cell based therapies in the field of bioelectrodes. It has been proposed that tissue engineering principles can be used to improve the integration of neural interfacing electrodes. Degradable hydrogels based on poly (vinyl alcohol) functionalised with tyramine (PVA-Tyr) have been shown to support covalent incorporation of non-modified tyrosine rich proteins within synthetic hydrogels. PVA-Tyr crosslinked with such proteins, were explored as a scaffold for supporting development of neural tissue in a three dimensional (3D) environment. In this study a model neural cell line (PC12) and glial accessory cell line, Schwann cell (SC) were encapsulated in PVA-Tyr crosslinked with gelatin and sericin. Specifically, this study aimed to examine the growth and function of SC and PC12 co-cultures when translated from a two dimensional (2D) environment to a 3D environment. PC12 differentiation was successfully promoted in both 2D and 3D at 25 days post-culture. SC encapsulated as a single cell line and in co-culture were able to produce both laminin and collagen-IV which are required to support neuronal development. Neurite outgrowth in the 3D environment was confirmed by immunocytochemical staining. PVA-Tyr/sericin/gelatin hydrogel showed mechanical properties similar to nerve tissue elastic modulus. It is suggested that the mechanical properties of the PVA-Tyr hydrogels with native protein components are providing with a compliant substrate that can be used to support the survival and differentiation of neural networks.
Goding JA, Gilmour AD, Martens PJ, et al., 2015, Small bioactive molecules as dual functional co-dopants for conducting polymers, Journal of Materials Chemistry B, Vol: 3, Pages: 5058-5069, ISSN: 2050-750X
© The Royal Society of Chemistry 2015. Biological responses to neural interfacing electrodes can be modulated via biofunctionalisation of conducting polymer (CP) coatings. This study investigated the use of small bioactive molecules with anti-inflammatory properties. Specifically, anionic dexamethasone phosphate (DP) and valproic acid (VA) were used to dope the CP poly(ethylenedioxythiophene) (PEDOT). The impact of DP and VA on material properties was explored both individually and together as a codoped system, compared to the conventional dopant p-toluenesulfonate (pTS). Electrical properties of DP and VA doped PEDOT were reduced in comparison to PEDOT/pTS, however co-doping with both DP and VA was shown to significantly improve the electroactivity of PEDOT in comparison the individually doped coatings. Similarly, while the individually doped PEDOT coatings were mechanically friable, the inclusion of both dopants during electropolymerisation was shown to attenuate this response. In a whole-blood model of inflammation all DP and VA doped CPs retained their bioactivity, causing a significant reduction in levels of the pro-inflammatory cytokine TNF-α. These studies demonstrated that small charged bioactive molecules are able act as dopants for CPs and that co-doping with ions of varied size and doping affinity may provide a means of addressing the limitations of large bulky bimolecular dopants.
Amella AD, Patton AJ, Martens PJ, et al., 2015, Freestanding, soft bioelectronics, Pages: 607-610, ISSN: 1948-3554
© 2015 IEEE. Soft, flexible electrode arrays are proposed to address the limitations of metallic tracks and electrodes in stimulating neuroprosthetics. The aim of these studies was to explore spatially selective polymerization of conductive polymer (CP) within a hydrogel as a proof of concept for freestanding conductive hydrogel electrode arrays, which are not bound to a metallic substrate. A suspension of CP chains within a non-conductive hydrogel was used to initiate subsequent electrochemical growth of highly conductive dense CP in patterned locations throughout the hydrogel volume. Tracks were produced and electroactivity was confirmed through an increase in charge storage capacity and a decrease in impedance. The electrochemical growth of poly(ethylene dioxythiophene) (PEDOT) was established visually and found to be constrained to the hydrogel track. Excitable cells, HL-1s were cultured on the hydrogel construct and found to attach and proliferate. Conductive hydrogels may provide an alternative to metals for producing soft bioelectronics.
Goding J, Green R, Martens P, et al., 2015, Bioactive conducting polymers for optimising the neural interface, Biointerfaces : Where Material Meets Biology, Publisher: Royal Society of Chemistry, Pages: 192-220, ISBN: 978-1-78262-845-3
Patton AJ, Green RA, Poole-Warren LA, 2015, Mediating conducting polymer growth within hydrogels by controlling nucleation, APL Materials, Vol: 3, ISSN: 2166-532X
This study examines the efficacy of primary and secondary nucleation for electrochemical polymerisation of conductive polymers within poly(vinyl alcohol) methacrylate hydrogels. The two methods of nucleation investigated were a primary heterogeneous mechanism via introduction of conductive bulk metallic glass (Mg 64 Zn 30 Ca 5 Na 1 ) particles and a secondary mechanism via introduction of "pre-polymerised" conducting polymer within the hydrogel (PEDOT:PSS). Evidence of nucleation was not seen in the bulk metallic glass loaded gels, however, the PEDOT:PSS loaded gels produced charge storage capacities over 15 mC/cm 2 when sufficient polymer was loaded. These studies support the hypothesis that secondary nucleation is an efficient approach to producing stand-alone conducting hydrogels.
Gilmour AD, Goding J, Poole-Warren LA, et al., 2015, In vitro biological assessment of electrode materials for neural interfaces, Pages: 450-453, ISSN: 1948-3554
© 2015 IEEE. The development of the next generation electrode interfaces for neural prosthetic devices requires high-through-put multifaceted testing strategies to assess material interactions with both peripheral and central nervous system (CNS) immune cells. The utility of a primary astrocyte enriched glial cell culture was assessed as a potential in vitro tool for understanding the immune response to electrode materials. Conductive polymer consisting of electropolymerized poly(3,4-ethylenedioxythiophene) (PEDOT) doped with paratoluene sulfonate (pTS) was used as a novel electrode material and compared to the conventional electrode material, platinum (Pt). Morphology of astrocytes and microglia in contact with the materials was analyzed and compared to an immunoassay of TNFα release from human blood plasma. While all electrode materials failed to stimulate TNFα release from human leukocytes, the materials in contact with glial cells resulted in progressive reactive gliosis. This primary astrocyte in vitro assay provides insight into the degeneration of electrode performance in vivo as a result of scar tissue reactions in chronic implant devices. It also highlights the relevance of testing for immune reactions with an appropriate cell system.
Shi A, Shemesh J, Asadnia M, et al., 2015, A novel microfluidic patterning device for neuron-glia co-culture, Pages: 633-635
� 15CBMS-0001. Many biological processes in the body are regulated by synchronized activity between two cell types. To study cell-cell interactions, it is necessary to develop easy to use co-culture systems, where different cell types can be cultured within the same confined space. Designing a complete 3D biomimetic system to study these interactions in vitro requires complex protocols and use of non-conventional materials such as hydrogels. This paper reports development of a temporarily sealed microfluidic device which utilizes a novel valve design to directly and accurately co-culture two cell lines in alternating rows, allowing them to proliferate towards each other and then observe their interaction at the boundaries of their interface.
Lim KS, Ramaswamy Y, Alves MH, et al., 2015, Optimization of crosslinking parameters for biosynthetic poly(Vinyl-alcohol)-tyramine hydrogels, Pages: 284-287, ISSN: 1680-0737
© Springer International Publishing Switzerland 2015. Photo-polymerizable hydrogels have been widely researched as tissue engineering matrices. When designing a new photo-crosslinkable, biosynthetic hydrogel system, a number of parameters need to be optimized, such as the polymerization conditions and amount of biological polymer included. This study aimed to investigate the crosslinking parameters (i.e., choice of initiator, light intensity and irradiation time), as well as the biological polymer (i.e., gelatin) content, for a degradable tyramine functionalized poly(vinyl alcohol) (PVA-Tyr) system. This PVA-Tyr can be photocrosslinked using a visible light initiated process composed of ruthenium (Ru) and persulfate compounds. Comparison of ammonium persulfate (APS) and sodium persulfate (SPS) showed that SPS supported fabrication of higher quality gels at lower concentrations than APS. The initiator concentration and irradiation conditions that were found to produce the best quality PVATyr gels were 2 mM Ru/20 mM SPS and 3 minutes of 15 mW/cm2 of visible light. Moreover, incorporation of gelatin into the PVA-Tyr gels successfully facilitated attachment of Schwann cells on the gels. The Schwann cells were able to survive and proliferate over 3 days on the PVA-Tyr/gelatin gels. Overall, this study showed that PVA-Tyr gels have high potential as biomaterials for tissue engineering applications.
Green RA, Matteucci PB, Dodds CWD, et al., 2014, Laser patterning of platinum electrodes for safe neurostimulation, Journal of Neural Engineering, Vol: 11, ISSN: 1741-2552
© 2014 IOP Publishing Ltd. Objective. Laser surface modification of platinum (Pt) electrodes was investigated for use in neuroprosthetics. Surface modification was applied to increase the surface area of the electrode and improve its ability to transfer charge within safe electrochemical stimulation limits. Approach. Electrode arrays were laser micromachined to produce Pt electrodes with smooth surfaces, which were then modified with four laser patterning techniques to produce surface structures which were nanosecond patterned, square profile, triangular profile and roughened on the micron scale through structured laser interference patterning (SLIP). Improvements in charge transfer were shown through electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and biphasic stimulation at clinically relevant levels. A new method was investigated and validat ed which enabled the assessment of in vivo electrochemically safe charge injection limits. Main results. All of the modified surfaces provided electrical advantage over the smooth Pt. The SLIP surface provided the greatest benefit both in vitro and in vivo, and this surface was the only type which had injection limits above the threshold for neural stimulation, at a level shown to produce a response in the feline visual cortex when using an electrode array implanted in the suprachoroidal space of the eye. This surface was found to be stable when stimulated with more than 150 million clinically relevant pulses in physiological saline. Significance. Critical to the assessment of implant devices is accurate determination of safe usage limits in an in vivo environment. Laser patterning, in particular SLIP, is a superior technique for improving the performance of implant electrodes without altering the interfacial electrode chemistry through coating. Future work will require chronic in vivo assessment of these electrode patterns.
Aregueta-Robles UA, Woolley AJ, Poole-Warren LA, et al., 2014, Organic electrode coatings for next-generation neural interfaces, Frontiers in Neuroengineering, Vol: 7, ISSN: 1662-6443
Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes. © 2014 Aregueta-Robles, Woolley, Poole-Warren, Lovell and Green.
Hassarati RT, Goding JA, Baek S, et al., 2014, Stiffness quantification of conductive polymers for bioelectrodes, Journal of Polymer Science, Part B: Polymer Physics, Vol: 52, Pages: 666-675, ISSN: 1099-0488
Conductive polymer (CP) coatings can improve the performance of metallic bioelectrodes in implantable devices, a benefit which is partially attributed to the "softer" material interface. However, due to the nature of CP fabrication on metallic substrates, accurate quantification of mechanical properties has been difficult to achieve. This study demonstrates that peak-force quantitative nanomechanical mapping (PF-QNM) is a robust technique for determining the modulus of CP coatings. The effect of dopant size, chemistry, and film hydration on the mechanical properties of poly(3,4-ethylene dioxythiophene) (PEDOT) is also examined. Analysis of PEDOT doped with poly(styrene sulfonate) produced across five different thicknesses confirms the utility of PF-QNM in yielding quantitative, repeatable moduli in both the dry and hydrated state. By doping PEDOT with paratoluene sulfonate and perchlorate (ClO 4 ) it is shown that the hydrophilicity and the size of the dopant are both critical factors influencing CP mechanical properties in the hydrated environment. © 2014 Wiley Periodicals, Inc.
Mario Cheong GL, Lim KS, Jakubowicz A, et al., 2014, Conductive hydrogels with tailored bioactivity for implantable electrode coatings, Acta Biomaterialia, Vol: 10, Pages: 1216-1226, ISSN: 1878-7568
The development of high-resolution neuroprosthetics has driven the need for better electrode materials. Approaches to achieve both electrical and mechanical improvements have included the development of hydrogel and conducting polymer composites. However, these composites have limited biological interaction, as they are often composed of synthetic polymers or non-ideal biological polymers, which lack the required elements for biorecognition. This study explores the covalent incorporation of bioactive molecules within a conducting hydrogel (CH). The CH was formed from the biosynthetic co-hydrogel poly(vinyl alcohol)-heparin and the conductive polymer (CP), poly(3,4-ethylene dioxythiophene). Adhesive biomolecules sericin and gelatin were covalently incorporated via methacrylate crosslinking within the CH. Electrical properties of the bioactive CH were assessed, and it was shown that the polar biomolecules improved charge transfer. The bioactivity of heparin within the hybrid assessed by examining stimulation of B-lymphocyte (BaF3) proliferation showed that bioactivity was retained after electropolymerization of the CP through the hydrogel. Similarly, incorporation of sericin and gelatin in the CH promoted neural cell adhesion and proliferation, with only small percentages (≤2 wt.%) required to achieve optimal results. Sericin provided the best support for the outgrowth of neural processes, and 1 wt.% was sufficient to facilitate adhesion and differentiation of neurons. The drug delivery capability of CH was shown through incorporation of nerve growth factor during polymer fabrication. NGF was delivered to the target cells, resulting in outgrowth of neural processes. The CH system is a flexible technology platform, which can be tailored to covalently incorporate bioactive protein sequences and deliver mobile water-soluble drug molecules. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Hassarati RT, Dueck WF, Tasche C, et al., 2014, Improving cochlear implant properties through conductive hydrogel coatings, IEEE Transactions on Neural Systems and Rehabilitation Engineering, Vol: 22, Pages: 411-418, ISSN: 1534-4320
Conductive hydrogel (CH) coatings for biomedical electrodes have shown considerable promise in improving electrode mechanical and charge transfer properties. While they have desirable properties as a bulk material, there is limited understanding of how these properties translate to a microelectrode array. This study evaluated the performance of CH coatings applied to Nucleus Contour Advance cochlear electrode arrays. Cyclic voltammetry and biphasic stimulation were carried out to determine electrical properties of the coated arrays. Electrical testing demonstrated that CH coatings supported up to 24 times increase in charge injection limit. Reduced impedance was also maintained for over 1 billion stimulations without evidence of delamination or degradation. Mechanical studies performed showed negligible effect of the coating on the pre-curl structure of the Contour Advance arrays. Testing the coating in a model human scala tympani confirmed that adequate contact was maintained across the lateral wall. CH coatings are a viable, stable coating for improving electrical properties of the platinum arrays while imparting a softer material interface to reduce mechanical mismatch. Ultimately, these coatings may act to minimize scar tissue formation and fluid accumulation around electrodes and thus improve the electrical performance of neural implants. © 2013 IEEE.
Baek S, Green RA, Poole-Warren LA, 2014, The biological and electrical trade-offs related to the thickness of conducting polymers for neural applications, Acta Biomaterialia, Vol: 10, Pages: 3048-3058, ISSN: 1878-7568
Poly(3,4-ethylenedioxythiophene) (PEDOT) films have attracted substantial interest as coatings for platinum neuroprosthetic electrodes due to their excellent chemical stability and electrical properties. This study systematically examined PEDOT coatings formed with different amounts of charge and dopant ions, and investigated the combination of surface characteristics that were optimal for neural cell interactions. PEDOT samples were fabricated by varying the electrodeposition charge from 0.05 to 1 C cm. Samples were doped with either poly(styrenesulfonate), tosylate (pTS) or perchlorate. Scanning electron micrographs revealed that both thickness and nodularity increased as the charge used to produce the sample was increased, and larger dopants produced smoother films across all thicknesses. X-ray photoelectron spectroscopy confirmed that the amount of charge directly corresponded to the thickness and amount of dopant in the samples. Additionally, with increased thickness and nodularity, the electrochemical properties of all PEDOT coatings improved. However, neural cell adhesion and outgrowth assays revealed that there is a direct biological tradeoff related to the thickness and nodularity. Cell attachment, growth and differentiation was poorer on the thicker, rougher samples, but thin, less nodular PEDOT films exhibited significant improvements over bare platinum. PEDOT/pTS fabricated with a charge density of <0.1 C cm provided superior electrochemical and biological properties over conventional platinum electrodes and would be the most suitable conducting polymer for neural interface applications. © 2014 Acta Materialia Inc.
Baek S, Green RA, Poole-Warren LA, 2014, Effects of dopants on the biomechanical properties of conducting polymer films on platinum electrodes, Journal of Biomedical Materials Research - Part A, Vol: 102, Pages: 2743-2754, ISSN: 1552-4965
Conducting polymers have often been described in literature as a coating for metal electrodes which will dampen the mechanical mismatch with neural tissue, encouraging intimate cell interactions. However, there is very limited quantitative analysis of conducting polymer mechanics and the relation to tissue interactions. This article systematically analyses the impact of coating platinum (Pt) electrodes with the conducting polymer poly(ethylene dioxythiophene) (PEDOT) doped with a series of common anions which have been explored for neural interfacing applications. Nanoindentation was used to determine the coating modulus and it was found that the polymer stiffness increased as the size of the dopant ion was increased, with PEDOT doped with polystyrene sulfonate (PSS) having the highest modulus at 3.2 GPa. This was more than double that of the ClO 4 doped PEDOT at 1.3 GPa. Similarly, the electrical properties of these materials were shown to have a size dependent behavior with the smaller anions producing PEDOT films with the highest charge transfer capacity and lowest impedance. Coating stiffness was found to have a negligible effect on in vitro neural cell survival and differentiation, but rather polymer surface morphology, dopant toxicity and mobility is found to have the greatest impact. © 2013 Wiley Periodicals, Inc.
Goding J, Green R, Martens P, et al., 2014, CHAPTER 8. Bioactive Conducting Polymers for Optimising the Neural Interface, Smart Materials Series, Publisher: Royal Society of Chemistry, Pages: 192-220
Baek S, Green R, Granville A, et al., 2013, Erratum: Thin film hydrophilic electroactive polymer coatings for bioelectrodes (Journal of Materials Chemistry B (2013) DOI:10.1039/C3TB20152J), Journal of Materials Chemistry B, Vol: 1, ISSN: 2050-750X
Green RA, Lim KS, Henderson WC, et al., 2013, Living electrodes: Tissue engineering the neural interface, Pages: 6957-6960, ISSN: 1557-170X
Soft, cell integrated electrode coatings are proposed to address the problem of scar tissue encapsulation of stimulating neuroprosthetics. The aim of these studies was to prove the concept and feasibility of integrating a cell loaded hydrogel with existing electrode coating technologies. Layered conductive hydrogel constructs are embedded with neural cells and shown to both support cell growth and maintain electro activity. The safe charge injection limit of these electrodes was 8 times higher than conventional platinum (Pt) electrodes and the stiffness was four orders of magnitude lower than Pt. Future studies will determine the biological cues required to support stem cell differentiation from the electrode surface. © 2013 IEEE.
Green RA, Guenther T, Jeschke C, et al., 2013, Integrated electrode and high density feedthrough system for chip-scale implantable devices, Biomaterials, Vol: 34, Pages: 6109-6118, ISSN: 1878-5905
High density feedthroughs have been developed which allow for the integration of chip-scale features and electrode arrays with up to 1141 stimulating sites to be located on a single implantable package. This layered technology displays hermetic properties and can be produced from as little as two laminated 200μm thick alumina sheets. It can also be expanded to a greater number of layers to allow flexible routing to integrated electronics. The microelectrodes, which are produced from sintered platinum (Pt) particulate, have high charge injection capacity as a result of a porous surface morphology. Despite their inherent porosity the electrodes are electrically stable following more than 1.8 billion stimulation pulses delivered at clinically relevant levels. The ceramic-Pt constructs are also shown to have acceptable biological properties, causing no cell growth inhibition using standard leachant assays and support neural cell survival and differentiation under both passive conditions and active electrical stimulation. © 2013.
Gilmour AD, Green RA, Thomson CE, 2013, A low-maintenance, primary cell culture model for the assessment of carbon nanotube toxicity, Toxicological and Environmental Chemistry, Vol: 95, Pages: 1129-1144, ISSN: 1029-0486
Carbon nanotubes (CNTs) have gained substantial interest as a material for biomedical devices with reliable properties suitable for electrically conducting biomedical devices. While CNTs combine ideal properties for a number of tissue-interfacing applications, their biocompatibility and safety have been the source of considerable conjecture. This study outlines a method for evaluating biocompatibility, using a low-cost, short-term assessment model of CNT with primary cells, which are more representative of an in vivo situation than cell lines. It was demonstrated that carboxylate-modified, multi-walled CNTs exhibit cytotoxic behavior in as little as 6 hr of exposure to primary fibroblasts. The resultant cell death was concentration dependent, demonstrating the efficacy of acute assessment of cytocompatibility. Although cell viability remained relatively high (being above 85% for all CNT concentrations up to 500 μg/ml), these results reflect similar relationships found for longer term exposures. This method has reliable potential for high-throughput assessment and quality control of CNTs in biomedical applications using a primary cell model. © 2013 © 2013 Taylor & Francis.
Green RA, Lim KS, Henderson WC, et al., 2013, Living electrodes: tissue engineering the neural interface, Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, Vol: 2013, Pages: 6957-6960, ISSN: 1557-170X
Soft, cell integrated electrode coatings are proposed to address the problem of scar tissue encapsulation of stimulating neuroprosthetics. The aim of these studies was to prove the concept and feasibility of integrating a cell loaded hydrogel with existing electrode coating technologies. Layered conductive hydrogel constructs are embedded with neural cells and shown to both support cell growth and maintain electro activity. The safe charge injection limit of these electrodes was 8 times higher than conventional platinum (Pt) electrodes and the stiffness was four orders of magnitude lower than Pt. Future studies will determine the biological cues required to support stem cell differentiation from the electrode surface.
Baek S, Green R, Granville A, et al., 2013, Thin film hydrophilic electroactive polymer coatings for bioelectrodes (vol 1, pg 3803, 2013), JOURNAL OF MATERIALS CHEMISTRY B, Vol: 1, Pages: 6670-6670, ISSN: 2050-7518
Baek S, Green RA, Granville A, et al., 2013, Thin film hydrophilic electroactive polymer coatings for bioelectrodes, Journal of materials chemistry. B, Materials for biology and medicine, Vol: 1, Pages: 3803-3810, ISSN: 2050-7518
Green RA, Hassarati RT, Bouchinet L, et al., 2012, Substrate dependent stability of conducting polymer coatings on medical electrodes, Biomaterials, Vol: 33, Pages: 5875-5886, ISSN: 1878-5905
Conducting polymer (CP) coatings on medical electrodes have the potential to provide superior performance when compared to conventional metallic electrodes, but their stability is strongly dependant on the substrate properties. The aim of this study was to examine the effect of laser roughening of underlying platinum (Pt) electrode surfaces on the mechanical, electrical and biological performance of CP coatings. In addition, the impact of dopant type on electrical performance and stability was assessed. The CP poly(ethylene dioxythiophene) (PEDOT) was coated on Pt microelectrode arrays, with three conventional dopant ions. The in vitro electrical characteristics were assessed by cyclic voltammetry and biphasic stimulation. Results showed that laser roughening of the underlying substrate did not affect the charge injection limit of the coated material, but significantly improved the passive stability and chronic stimulation lifetime without failure of the coating. Accelerated material ageing and long-term biphasic stimulus studies determined that some PEDOT variants experienced delamination within as little as 10 days when the underlying Pt was smooth, but laser roughening to produce a surface index of 2.5 improved stability, such that more than 1.3 billion stimulation cycles could be applied without evidence of failure. PEDOT doped with paratoluene sulfonate (PEDOT/pTS) was found to be the most stable CP on roughened Pt, and presented a surface topography which encouraged neural cell attachment. © 2012.
Green RA, Hassarati RT, Goding JA, et al., 2012, Macromol. Biosci. 4/2012, Macromolecular Bioscience, Vol: 12, Pages: n/a-n/a, ISSN: 1616-5187
Poole-Warren LA, Goding J, Green RA, et al., 2012, Challenges of therapeutic delivery using conducting polymers, Therapeutic Delivery, Vol: 3, Pages: 421-427, ISSN: 2041-5990
Green RA, Matteucci P, Hassarati R, et al., 2012, Performance of conducting polymer electrodes for stimulating neuroprosthetics, Journal of neural engineering, Vol: 10, Pages: 1-11, ISSN: 1741-2552
Objective. Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. Approach. PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. Main results. It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. Significance. These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.
Green RA, Hassarati R, Goding J, et al., 2012, Conductive Hydrogels: Mechanically Robust Hybrids for Use as Biomaterials, Macromolecular Bioscience, Vol: 12, Pages: 494-501, ISSN: 1616-5187
A hybrid system for producing conducting polymers within a doping hydrogel mesh is presented. These conductive hydrogels demonstrate comparable electroactivity to conventional conducting polymers without requiring the need for mobile doping ions which are typically used in literature. These hybrids have superior mechanical stability and a modulus significantly closer to neural tissue than materials which are commonly used for medical electrodes. Additionally they are shown to support the attachment and differentiation of neural like cells, with improved interaction when compared to homogeneous hydrogels. The system provides flexibility such that biologic incorporation can be tailored for application.
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