76 results found
Palmer JC, Green RA, Boscher F, et 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
Cuttaz E, Goding J, Vallejo-Giraldo C, et 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.
Aregueta-Robles UA, Martens PJ, Poole-Warren LA, et al., 2018, Tissue engineered hydrogels supporting 3D neural networks., Acta Biomater
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
Green R, 2018, Are ‘next generation’ bioelectronics being designed using old technologies?, Bioelectronics in Medicine, Vol: 1, Pages: 171-174, ISSN: 2059-1500
Gilmour A, Goding J, Robles UA, et 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.
Goding JA, Gilmour AD, Aregueta-Robles UA, et al., 2018, Living Bioelectronics: Strategies for Developing an Effective Long-Term Implant with Functional Neural Connections, ADVANCED FUNCTIONAL MATERIALS, Vol: 28, ISSN: 1616-301X
Aregueta-Robles UA, Martens PJ, Poole-Warren LA, et 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: 0887-6266
Green RA, 2018, Conductive hydrogel electrodes for delivery of long-term high frequency pulses, Frontiers in Neuroscience, Vol: 11, ISSN: 1662-4548
© 2018 Staples, Goding, Gilmour, Aristovich, Byrnes-Preston, Holder, Morley, Lovell, Chew and Green. 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.
Goding J, Vallejo-Giraldo C, Syed O, et al., Considerations for Applications of Hydrogels in Bioelectronics, Journal of Materials Chemistry B, ISSN: 2050-750X
<p>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...</p>
Goding J, Gilmour A, Robles UA, et al., 2017, A living electrode construct for incorporation of cells into bionic devices, MRS COMMUNICATIONS, Vol: 7, Pages: 487-495, ISSN: 2159-6859
Goding J, Gilmour A, Martens P, et al., 2017, Interpenetrating Conducting Hydrogel Materials for Neural Interfacing Electrodes, ADVANCED HEALTHCARE MATERIALS, Vol: 6, ISSN: 2192-2640
Palmer JC, Lord MS, Pinyon JL, et al., 2016, Understanding the cochlear implant environment by mapping perilymph proteomes from different species, 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.
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
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.
Patton AJ, Poole-Warren LA, Green RA, 2016, Mechanisms for Imparting Conductivity to Nonconductive Polymeric Biomaterials, MACROMOLECULAR BIOSCIENCE, Vol: 16, Pages: 1103-1121, ISSN: 1616-5187
Gilmour AD, Woolley AJ, Poole-Warren LA, et al., 2016, A critical review of cell culture strategies for modelling intracortical brain implant material reactions., Biomaterials, Vol: 91, Pages: 23-43
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.
Hassarati RT, Marcal H, John L, et al., 2016, Biofunctionalization of conductive hydrogel coatings to support olfactory ensheathing cells at implantable electrode interfaces, 6th Indo-Australian Conference on Biomaterials, Tissue Engineering, Drug Delivery System and Regenerative Medicine, Publisher: WILEY-BLACKWELL, Pages: 712-722, ISSN: 1552-4973
Roberts JJ, Farrugia BL, Green RA, et 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, Journal of Tissue Engineering, Vol: 7, Pages: 204173141667713-204173141667713, ISSN: 2041-7314
Josef G, Rylie G, Laura P-W, 2016, Soft and flexible electroactive materials for neuroprosthetic devices, Frontiers in Bioengineering and Biotechnology, Vol: 4
Rachelle H, L John F, Maria A, et al., 2016, Electrical stimulation of cells in living bioelectronic devices, Frontiers in Bioengineering and Biotechnology, Vol: 4
Alexander P, Rylie G, Laura P-W, 2016, Covalent incorporation of biomolecules for improving functional properties of freestanding conductive hydrogels, Frontiers in Bioengineering and Biotechnology, Vol: 4
Green R, Abidian MR, 2015, Conducting Polymers for Neural Prosthetic and Neural Interface Applications, ADVANCED MATERIALS, Vol: 27, Pages: 7620-7637, ISSN: 0935-9648
, 2015, 11 - Biosynthetic conductive polymer composites for tissue-engineering biomedical devices, Biosynthetic Polymers for Medical Applications, Pages: 277-298, ISBN: 9781782421139
© 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.
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.
, 2015, Small bioactive molecules as dual functional co-dopants for conducting polymers, Journal of Materials Chemistry B, Vol: 3, Pages: 5058-5069, ISSN: 2050-7518
© 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.
, 2015, Bioactive conducting polymers for optimising the neural interface, Pages: 192-220
© 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.
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.
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