Imperial College London

DrRylieGreen

Faculty of EngineeringDepartment of Bioengineering

Reader in Polymer Bioelectronics
 
 
 
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+44 (0)20 7594 0943rylie.green

 
 
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2.06Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
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77 results found

Palmer JC, Green RA, Boscher F, Poole-Warren LA, Carter PM, Enke YL, Lovell NH, Lord MSet al., 2019, Development and performance of a biomimetic artificial perilymph for in vitro testing of medical devices, JOURNAL OF NEURAL ENGINEERING, Vol: 16, ISSN: 1741-2560

Journal article

Goding J, Vallejo-Giraldo C, Syed O, Green Ret al., 2019, Considerations for hydrogel applications to neural bioelectronics, Journal of Materials Chemistry B, Vol: 7, Pages: 1625-1636, ISSN: 2050-7518

© 2019 The Royal Society of Chemistry. Hydrogels have been applied across a wide range of biomedical applications due to their versatility, but more recently have garnered interest as materials in bioelectronics due to the capacity to tailor their mechanical and biological properties. Hydrogel coatings in particular have been used to impart softness at the bionic device interface, deliver therapeutics and control cell interactions through presentation of peptides and growth factors. Additionally, the use of dynamic hydrogel properties has been harnessed as shuttles for the implantation of flexible electrode arrays. In all of these applications, the hydrogel must be designed not only to provide the desired performance, but also have no unexpected impacts on the surrounding tissues, such as extensive swelling that can compress the cells at the interface. Appropriate selection and design of hydrogel systems for bioelectronics requires an understanding of the physical, chemical and biological properties of hydrogels as well as their structure-property relationships. This review covers the design rationale for application of hydrogels systems for use in bioelectronic devices with a focus on in vivo applications.

Journal article

Cuttaz E, Goding J, Vallejo-Giraldo C, Aregueta-Robles U, Lovell N, Ghezzi D, Green RAet al., 2019, Conductive elastomer composites for fully polymeric, flexible bioelectronics., Biomater Sci

Flexible polymeric bioelectronics have the potential to address the limitations of metallic electrode arrays by minimizing the mechanical mismatch at the device-tissue interface for neuroprosthetic applications. This work demonstrates the straightforward fabrication of fully organic electrode arrays based on conductive elastomers (CEs) as a soft, flexible and stretchable electroactive composite material. CEs were designed as hybrids of polyurethane elastomers (PU) and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), with the aim of combining the electrical properties of PEDOT:PSS with the mechanical compliance of elastomers. CE composites were fabricated by solvent casting of PEDOT:PSS dispersed in dissolved PU at different conductive polymer (CP) loadings, from 5 wt% to 25 wt%. The formation of PEDOT:PSS networks within the PU matrix and the resultant composite material properties were examined as a function of CP loading. Increased PEDOT:PSS loading was found to result in a more connected network within the PU matrix, resulting in increased conductivity and charge storage capacity. Increased CP loading was also determined to increase the Young's modulus and reduce the strain at failure. Biological assessment of CE composites showed them to mediate ReNcell VM human neural precursor cell adhesion. The increased stiffness of CE films was also found to promote neurite outgrowth. CE sheets were directly laser micromachined into a functional array and shown to deliver biphasic waveforms with comparable voltage transients to Pt arrays in in vitro testing.

Journal article

Green R, 2019, Elastic and conductive hydrogel electrodes, NATURE BIOMEDICAL ENGINEERING, Vol: 3, Pages: 9-10, ISSN: 2157-846X

Journal article

Aregueta-Robles UA, Martens PJ, Poole-Warren LA, Green RAet al., 2018, Tissue engineered hydrogels supporting 3D neural networks, Acta Biomaterialia, ISSN: 1742-7061

Promoting nerve regeneration requires engineering cellular carriers to physically and biochemically support neuronal growth into a long lasting functional tissue. This study systematically evaluated the capacity of a biosynthetic poly(vinyl alcohol) (PVA) hydrogel to support growth and differentiation of co-encapsulated neurons and glia. A significant challenge is to understand the role of the dynamic degradable hydrogel mechanical properties on expression of relevant cellular morphologies and function. It was hypothesised that a carrier with mechanical properties akin to neural tissue will provide glia with conditions to thrive, and that glia in turn will support neuronal survival and development. PVA co-polymerised with biological macromolecules sericin and gelatin (PVA-SG) and with tailored nerve tissue-like mechanical properties were used to encapsulate Schwann cells (SCs) alone and subsequently a co-culture of SCs and neural-like PC12s. SCs were encapsulated within two PVA-SG gel variants with initial compressive moduli of 16 kPa and 2 kPa, spanning a range of reported mechanical properties for neural tissues. Both hydrogels were shown to support cell viability and expression of extracellular matrix proteins, however, SCs grown within the PVA-SG with a higher initial modulus were observed to present with greater physiologically relevant morphologies and increased expression of extracellular matrix proteins. The higher modulus PVA-SG was subsequently shown to support development of neuronal networks when SCs were co-encapsulated with PC12s. The lower modulus hydrogel was unable to support effective development of neural networks. This study demonstrates the critical link between hydrogel properties and glial cell phenotype on development of functional neural tissues. STATEMENT OF SIGNIFICANCE: Hydrogels as platforms for tissue regeneration must provide encapsulated cellular progenitors with physical and biochemical cues for initial survival and to support ongoin

Journal article

Green R, 2018, Are ‘next generation’ bioelectronics being designed using old technologies?, Bioelectronics in Medicine, Vol: 1, Pages: 171-174, ISSN: 2059-1500

Journal article

Gilmour A, Goding J, Robles UA, Staples N, Byrnes-Preston P, Morley J, Lovell NH, Chew DJ, Green Ret al., 2018, Stimulation of peripheral nerves using conductive hydrogel electrodes., Conf Proc IEEE Eng Med Biol Soc, Vol: 2018, Pages: 5475-5478, ISSN: 1557-170X

Nerve block via electrical stimulation of nerves requires a device capable of transferring large amounts of charge across the neural interface on chronic time scales. Current metal electrode designs are limited in their ability to safely and effectively deliver this charge in a stable manner. Conductive hydrogel (CH) coatings are a promising alternative to metal electrodes for neural interfacing devices. This study assessed the performance of CH electrodes compared to platinum-iridium (PtIr) electrodes in commercial nerve cuff devices in both the in vitro and acute in vivo environments. CH electrodes were found to have higher charge storage capacities and lower impedances compared to bare PtIr electrodes. Application of CH coatings also resulted in a three-fold increase in in vivo charge injection limit. These significant improvements in electrochemical properties will allow for the design of smaller and safer stimulating devices for nerve block applications.

Journal article

Goding JA, Gilmour AD, Aregueta-Robles UA, Hasan EA, Green RAet al., 2018, Living Bioelectronics: Strategies for Developing an Effective Long-Term Implant with Functional Neural Connections, Advanced Functional Materials, Vol: 28, ISSN: 1616-3028

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Existing bionic implants use metal electrodes, which have low charge transfer capacity and poor tissue integration. This limits their use in next-generation, high resolution devices. Coating and other modification techniques have been explored to improve the performance of metal electrodes. While this has enabled increased charge transfer properties and integration of biologically responsive components, stable long term performance remains a significant challenge. This progress report provides a background on electrode modification techniques, exploring state-of-the art approaches to improving implantable electrodes. The new frontier of cell-based electronics, is introduced detailing approaches that use tissue engineering principles applied to bionic devices. These living bioelectronic technologies aim to enable devices to grow into target tissues, creating direct neural connections. Ideally, this approach will create a paradigm shift in biomedical electrode design. Rather than relying on unwieldy metal electrodes and direct current injection, living bioelectronics will use cells embedded within devices to provide communication through synaptic connections. This report details the challenge of designing electrodes that can bridge the technology gap between conventional metal electrode interfaces and new living electrodes through considering electrical, chemical, physical and biological characteristics.

Journal article

Aregueta-Robles UA, Martens PJ, Poole-Warren LA, Green RAet al., 2018, Tailoring 3D hydrogel systems for neuronal encapsulation in living electrodes, Journal of Polymer Science, Part B: Polymer Physics, Vol: 56, Pages: 273-287, ISSN: 1099-0488

© 2017 Wiley Periodicals, Inc. State-of-the-art neurorprostheses rely on stiff metallic electrodes to communicate with neural tissues. It was envisioned that a soft, organic electrode coating embedded with functional neural cells will enhance electrode-tissue integration. To enable such a device, it is necessary to produce a cell scaffold with mechanical properties matched to native neural tissue. A degradable poly(vinyl alcohol) (PVA) hydrogel was tailored to have a range of compressive moduli through variation in macromer composition and initiator amount. A regression model was used to predict the amount of initiator required for hydrogel polymerization with nominal macromer content ranging between 5 and 20 wt %. Hydrogels at 5 and 10 wt % were reliably formed but 15 wt % and above were not able to be fabricated due to the light attenuation properties of the initiator ruthenium at increased concentration. Compressive modulus of hydrogels decreased upon incorporation of biomolecules (sericin and gelatin), however, the bulk stiffness spanned the range required to match neural tissue properties (0.04–20kPa). Neuroglia cells, such as Schwann cells survived and grew within the scaffold. The significant finding of this work is that the PVA-tyramine system can be tuned to provide a soft degradable scaffold for neural tissue regeneration while presenting bioactive molecules for cellular expansion. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 273–287.

Journal article

Staples NA, Goding JA, Gilmour AD, Aristovich KY, Byrnes-Preston P, Holder DS, Morley JW, Lovell NH, Chew DJ, Green RAet al., 2018, Conductive hydrogel electrodes for delivery of long-term high frequency pulses, Frontiers in Neuroscience, Vol: 11, ISSN: 1662-453X

Nerve block waveforms require the passage of large amounts of electrical energy at the neural interface for extended periods of time. It is desirable that such waveforms be applied chronically, consistent with the treatment of protracted immune conditions, however current metal electrode technologies are limited in their capacity to safely deliver ongoing stable blocking waveforms. Conductive hydrogel (CH) electrode coatings have been shown to improve the performance of conventional bionic devices, which use considerably lower amounts of energy than conventional metal electrodes to replace or augment sensory neuron function. In this study the application of CH materials was explored, using both a commercially available platinum iridium (PtIr) cuff electrode array and a novel low-cost stainless steel (SS) electrode array. The CH was able to significantly increase the electrochemical performance of both array types. The SS electrode coated with the CH was shown to be stable under continuous delivery of 2 mA square pulse waveforms at 40,000 Hz for 42 days. CH coatings have been shown as a beneficial electrode material compatible with long-term delivery of high current, high energy waveforms.

Journal article

Palmer JC, Lord MS, Pinyon JL, Wise AK, Lovell NH, Carter PM, Enke YL, Housley GD, Green RAet al., 2018, Comparing perilymph proteomes across species, Laryngoscope, Vol: 128, Pages: E47-E52, ISSN: 1531-4995

© 2017 The American Laryngological, Rhinological and Otological Society, Inc. Objectives/Hypothesis: Biological components of perilymph affect the electrical performance of cochlear implants. Understanding the perilymph composition of common animal models will improve the understanding of this impact and improve the interpretation of results from animal studies and how it relates to humans. Study Design: Analysis and comparison of the proteomes of human, guinea pig, and cat perilymph. Methods: Multiple perilymph samples from both guinea pigs and cats were analysed via liquid chromatography with tandem mass spectrometry. Proteins were identified using the Mascot database. Human data were obtained from a published dataset. Proteins identified were refined to form a proteome for each species. Results: Over 200 different proteins were found per species. There were 81, 39, and 64 proteins in the final human, guinea pig, and cat proteomes, respectively. Twenty-one proteins were common to all three species. Fifty-two percent of the cat proteome was found in the human proteome, and 31% of the guinea pig was common to human. The cat proteome had similar complexity to the human proteome in three protein classes, whereas the guinea pig had a similar complexity in two. The presence of albumin was significantly higher in human perilymph than in the other two species. Immunoglobulins were more abundant in the human than in the cat proteome. Conclusions: Perilymph proteomes were compared across three species. The degree of crossover of proteins of both guinea pig and cat with human indicate that these animals suitable models for the human cochlea, albeit the cat perilymph is a closer match. Level of Evidence: NA. Laryngoscope, 128:E47–E52, 2018.

Journal article

Goding J, Gilmour A, Robles UA, Poole-Warren L, Lovell N, Martens P, Green Ret al., 2017, A living electrode construct for incorporation of cells into bionic devices, MRS Communications, Vol: 7, Pages: 487-495, ISSN: 2159-6867

© 2017 Materials Research Society. A living electrode construct that enables integration of cells within bionic devices has been developed. The layered construct uses a combination of non-degradable conductive hydrogel and degradable biosynthetic hydrogel to support cell encapsulation at device surfaces. In this study, the material system is designed and analyzed to understand the impact of the cell carrying component on electrode characteristics. The cell carrying layer is shown to provide a soft interface that supports extracellular matrix development within the electrode while not significantly reducing the charge transfer characteristics. The living layer was shown to degrade over 21 days with minimal swelling upon implantation.

Journal article

Goding J, Gilmour A, Martens P, Poole-Warren L, Green Ret al., 2017, Interpenetrating Conducting Hydrogel Materials for Neural Interfacing Electrodes, Advanced Healthcare Materials, Vol: 6, ISSN: 2192-2659

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Conducting hydrogels (CHs) are an emerging technology in the field of medical electrodes and brain–machine interfaces. The greatest challenge to the fabrication of CH electrodes is the hybridization of dissimilar polymers (conductive polymer and hydrogel) to ensure the formation of interpenetrating polymer networks (IPN) required to achieve both soft and electroactive materials. A new hydrogel system is developed that enables tailored placement of covalently immobilized dopant groups within the hydrogel matrix. The role of immobilized dopant in the formation of CH is investigated through covalent linking of sulfonate doping groups to poly(vinyl alcohol) (PVA) macromers. These groups control the electrochemical growth of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and subsequent material properties. The effect of dopant density and interdopant spacing on the physical, electrochemical, and mechanical properties of the resultant CHs is examined. Cytocompatible PVA hydrogels with PEDOT penetration throughout the depth of the electrode are produced. Interdopant spacing is found to be the key factor in the formation of IPNs, with smaller interdopant spacing producing CH electrodes with greater charge storage capacity and lower impedance due to increased PEDOT growth throughout the network. This approach facilitates tailorable, high-performance CH electrodes for next generation, low impedance neuroprosthetic devices.

Journal article

Palmer JC, Lord MS, Pinyon JL, Wise AK, Lovell NH, Carter PM, Enke YL, Housley GD, Green RAet al., 2016, Understanding the cochlear implant environment by mapping perilymph proteomes from different species, 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Pages: 5237-5240, ISSN: 1557-170X

© 2016 IEEE. Cochlear implants operate within a bony channel of the cochlea, bathed in a fluid known as the perilymph. The perilymph is a complex fluid containing ions and proteins, which are known to actively interact with metallic electrodes. To improve our understanding of how cochlear implant performance varies in preclinical in vivo studies in comparison to human trials and patient outcomes, the protein composition (or perilymph proteome) is needed. Samples of perilymph were gathered from feline and Guinea pig subjects and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to produce proteomes and compare against the recently published human proteome. Over 64% of the proteins in the Guinea pig proteome were found to be common to the human proteome. The proportions of apolipoproteins, enzymes and immunoglobulins showed little variation between the two proteomes, with other classes showing similarity. This establishes a good basis for comparison of results. The results for the feline profile showed less similarity with the human proteome and would not provide a quality comparison. This work highlights the suitability of the Guinea pig to model the biological environment of the human cochlear and the need to carefully select models of the biological environment of a cochlear implant to more adequately translate in vitro and in vivo studies to the clinic.

Conference paper

Hassarati RT, Foster LJR, Green RA, 2016, Influence of biphasic stimulation on olfactory ensheathing cells for neuroprosthetic devices, Frontiers in Neuroscience, Vol: 10, ISSN: 1662-453X

� 2016 Hassarati, Foster and Green. The recent success of olfactory ensheathing cell (OEC) assisted regeneration of injured spinal cord has seen a rising interest in the use of these cells in tissue-engineered systems. Previously shown to support neural cell growth through glial scar tissue, OECs have the potential to assist neural network formation in living electrode systems to produce superior neuroprosthetic electrode surfaces. The following study sought to understand the influence of biphasic electrical stimulation (ES), inherent to bionic devices, on cell survival and function, with respect to conventional metallic and developmental conductive hydrogel (CH) coated electrodes. The CH utilized in this study was a biosynthetic hydrogel consisting of methacrylated poly(vinyl-alcohol) (PVA), heparin and gelatin through which poly(3,4-ethylenedioxythiophene) (PEDOT) was electropolymerised. OECs cultured on Pt and CH surfaces were subjected to biphasic ES. Image-based cytometry yielded little significant difference between the viability and cell cycle of OECs cultured on the stimulated and passive samples. The significantly lower voltages measured across the CH electrodes (147 � 3 mV) compared to the Pt (317 � 5 mV), had shown to influence a higher percentage of viable cells on CH (91-93%) compared to Pt (78-81%). To determine the functionality of these cells following electrical stimulation, OECs co-cultured with PC12 cells were found to support neural cell differentiation (an indirect measure of neurotrophic factor production) following ES.

Journal article

Cogan SF, Garrett DJ, Green RA, 2016, Electrochemical Principles of Safe Charge Injection, Neurobionics: The Biomedical Engineering of Neural Prostheses, Pages: 55-88, ISBN: 9781118816028

© 2016 John Wiley & Sons, Inc. All rights reserved. Summary: Proper selection of stimulation parameters, such as the pulse frequency, pulse width and the duty cycle, is important during charge injection for obtaining the desired functional response and ensuring that the stimulation is delivered without electrode corrosion or tissue damage. This chapter describes two categories of charge transfer at the electrode-tissue interface: capacitive charge transfer by double-layer charging, and Faradaic charge transfer in which species are oxidized or reduced. Lists of electrode materials suitable for chronic recording and stimulation are limited to platinum and its alloys with iridium, porous titanium nitride and, to a lesser extent, iridium oxide, and some stainless steels. The chapter then discusses the factors influencing electrode reversibility. Emerging electrode coatings based on intrinsically conducting polymers, carbon nanotubes (CNTs), doped ultra-nano-crystalline diamond and graphene are also discussed. Highlights of the properties of those more conventional electrode materials are finally presented.

Book chapter

Patton AJ, Poole-Warren LA, Green RA, 2016, Mechanisms for Imparting Conductivity to Nonconductive Polymeric Biomaterials, Macromolecular Bioscience, Pages: 1103-1121, ISSN: 1616-5195

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Traditionally, conductive materials for electrodes are based on high modulus metals or alloys. Development of bioelectrodes that mimic the mechanical properties of the soft, low modulus tissues in which they are implanted is a rapidly expanding field of research. Many polymers exist that more closely match tissue mechanics than metals; however, the majority do not conduct charge. Integrating conductive properties via incorporation of metals and other conductors into nonconductive polymers is a successful approach to producing polymers that can be used in electrical interfacing devices. When combining conductive materials with nonconductive polymer matrices, there is often a tradeoff between the electrical and mechanical properties. This review analyzes the advantages and disadvantages of approaches involving coating or layer formation, composite formation via dispersion of conductive inclusions through polymer matrices, and in situ growth of a conductive network within polymers. (Figure presented.).

Journal article

Gilmour AD, Woolley AJ, Poole-Warren LA, Thomson CE, Green RAet al., 2016, A critical review of cell culture strategies for modelling intracortical brain implant material reactions, Biomaterials, Vol: 91, Pages: 23-43, ISSN: 1878-5905

© 2016 Elsevier Ltd. The capacity to predict in vivo responses to medical devices in humans currently relies greatly on implantation in animal models. Researchers have been striving to develop in vitro techniques that can overcome the limitations associated with in vivo approaches. This review focuses on a critical analysis of the major in vitro strategies being utilized in laboratories around the world to improve understanding of the biological performance of intracortical, brain-implanted microdevices. Of particular interest to the current review are in vitro models for studying cell responses to penetrating intracortical devices and their materials, such as electrode arrays used for brain computer interface (BCI) and deep brain stimulation electrode probes implanted through the cortex. A background on the neural interface challenge is presented, followed by discussion of relevant in vitro culture strategies and their advantages and disadvantages. Future development of 2D culture models that exhibit developmental changes capable of mimicking normal, postnatal development will form the basis for more complex accurate predictive models in the future. Although not within the scope of this review, innovations in 3D scaffold technologies and microfluidic constructs will further improve the utility of in vitro approaches.

Journal article

Hassarati RT, Marcal H, John L, Foster R, Green RAet al., 2016, Biofunctionalization of conductive hydrogel coatings to support olfactory ensheathing cells at implantable electrode interfaces, Journal of Biomedical Materials Research - Part B Applied Biomaterials, Pages: 712-722, ISSN: 1552-4981

© 2015 Wiley Periodicals, Inc. Mechanical discrepancies between conventional platinum (Pt) electrodes and neural tissue often result in scar tissue encapsulation of implanted neural recording and stimulating devices. Olfactory ensheathing cells (OECs) are a supportive glial cell in the olfactory nervous system which can transition through glial scar tissue while supporting the outgrowth of neural processes. It has been proposed that this function can be used to reconnect implanted electrodes with the target neural pathways. Conductive hydrogel (CH) electrode coatings have been proposed as a substrate for supporting OEC survival and proliferation at the device interface. To determine an ideal CH to support OECs, this study explored eight CH variants, with differing biochemical composition, in comparison to a conventional Pt electrodes. All CH variants were based on a biosynthetic hydrogel, consisting of poly(vinyl alcohol) and heparin, through which the conductive polymer (CP) poly(3,4-ethylenedioxythiophene) was electropolymerized. The biochemical composition was varied through incorporation of gelatin and sericin, which were expected to provide cell adherence functionality, supporting attachment, and cell spreading. Combinations of these biomolecules varied from 1 to 3 wt %. The physical, electrical, and biological impact of these molecules on elect rode performance was assessed. Cyclic voltammetry and electrochemical impedance spectroscopy demonstrated that the addition of these biological molecules had little significant effect on the coating's ability to safely transfer charge. Cell attachment studies, however, determined that the incorporation of 1 wt % gelatin in the hydrogel was sufficient to significantly increase the attachment of OECs compared to the nonfunctionalized CH.

Conference paper

Roberts JJ, Farrugia BL, Green RA, Rnjak-Kovacina J, Martens PJet al., 2016, In situ formation of poly(vinyl alcohol)-heparin hydrogels for mild encapsulation and prolonged release of basic fibroblast growth factor and vascular endothelial growth factor., J Tissue Eng, Vol: 7, ISSN: 2041-7314

Heparin-based hydrogels are attractive for controlled growth factor delivery, due to the native ability of heparin to bind and stabilize growth factors. Basic fibroblast growth factor and vascular endothelial growth factor are heparin-binding growth factors that synergistically enhance angiogenesis. Mild, in situ encapsulation of both basic fibroblast growth factor and vascular endothelial growth factor and subsequent bioactive dual release has not been demonstrated from heparin-crosslinked hydrogels, and the combined long-term delivery of both growth factors from biomaterials is still a major challenge. Both basic fibroblast growth factor and vascular endothelial growth factor were encapsulated in poly(vinyl alcohol)-heparin hydrogels and demonstrated controlled release. A model cell line, BaF32, was used to show bioactivity of heparin and basic fibroblast growth factor released from the gels over multiple days. Released basic fibroblast growth factor promoted higher human umbilical vein endothelial cell outgrowth over 24 h and proliferation for 3 days than the poly(vinyl alcohol)-heparin hydrogels alone. The release of vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels promoted human umbilical vein endothelial cell outgrowth but not significant proliferation. Dual-growth factor release of basic fibroblast growth factor and vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels resulted in a synergistic effect with significantly higher human umbilical vein endothelial cell outgrowth compared to basic fibroblast growth factor or vascular endothelial growth factor alone. Poly(vinyl alcohol)-heparin hydrogels allowed bioactive growth factor encapsulation and provided controlled release of multiple growth factors which is beneficial toward tissue regeneration applications.

Journal article

Ulises AR, Khoon L, Penny M, Nigel L, Laura PW, Rylie Get al., 2016, Tissue engineering cell-based bioelectronics, Frontiers in Bioengineering and Biotechnology, ISSN: 2296-4185

Conference paper

Josef G, Rylie G, Laura PW, 2016, Soft and flexible electroactive materials for neuroprosthetic devices, Frontiers in Bioengineering and Biotechnology, Vol: 4, ISSN: 2296-4185

Journal article

Alexander P, Rylie G, Laura PW, 2016, Covalent incorporation of biomolecules for improving functional properties of freestanding conductive hydrogels, Frontiers in Bioengineering and Biotechnology, Vol: 4, ISSN: 2296-4185

Journal article

Rachelle H, L John F, Maria A, Rylie Get al., 2016, Electrical stimulation of cells in living bioelectronic devices, Frontiers in Bioengineering and Biotechnology, Vol: 4, ISSN: 2296-4185

Journal article

Green R, Abidian MR, 2015, Conducting Polymers for Neural Prosthetic and Neural Interface Applications, Advanced materials (Deerfield Beach, Fla.), Vol: 27, Pages: 7620-7637, ISSN: 1521-4095

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Neural-interfacing devices are an artificial mechanism for restoring or supplementing the function of the nervous system, lost as a result of injury or disease. Conducting polymers (CPs) are gaining significant attention due to their capacity to meet the performance criteria of a number of neuronal therapies including recording and stimulating neural activity, the regeneration of neural tissue and the delivery of bioactive molecules for mediating device-tissue interactions. CPs form a flexible platform technology that enables the development of tailored materials for a range of neuronal diagnostic and treatment therapies. In this review, the application of CPs for neural prostheses and other neural interfacing devices is discussed, with a specific focus on neural recording, neural stimulation, neural regeneration, and therapeutic drug delivery.

Journal article

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.

Book chapter

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.

Book

Aregueta-Robles UA, Lim KS, Martens PJ, Lovell NH, Poole-Warren LA, Green Ret 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.

Conference paper

Goding JA, Gilmour AD, Martens PJ, Poole-Warren LA, Green RAet 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.

Journal article

Goding J, Green R, Martens P, Poole-Warren Let 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

Book chapter

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