86 results found
Peressotti S, Koehl GE, Goding JA, et al., 2021, Self-Assembling Hydrogel Structures for Neural Tissue Repair., ACS Biomater Sci Eng
Hydrogel materials have been employed as biological scaffolds for tissue regeneration across a wide range of applications. Their versatility and biomimetic properties make them an optimal choice for treating the complex and delicate milieu of neural tissue damage. Aside from finely tailored hydrogel properties, which aim to mimic healthy physiological tissue, a minimally invasive delivery method is essential to prevent off-target and surgery-related complications. The specific class of injectable hydrogels termed self-assembling peptides (SAPs), provide an ideal combination of in situ polymerization combined with versatility for biofunctionlization, tunable physicochemical properties, and high cytocompatibility. This review identifies design criteria for neural scaffolds based upon key cellular interactions with the neural extracellular matrix (ECM), with emphasis on aspects that are reproducible in a biomaterial environment. Examples of the most recent SAPs and modification methods are presented, with a focus on biological, mechanical, and topographical cues. Furthermore, SAP electrical properties and methods to provide appropriate electrical and electrochemical cues are widely discussed, in light of the endogenous electrical activity of neural tissue as well as the clinical effectiveness of stimulation treatments. Recent applications of SAP materials in neural repair and electrical stimulation therapies are highlighted, identifying research gaps in the field of hydrogels for neural regeneration.
Cuttaz EA, Chapman CAR, Syed O, et al., 2021, Stretchable, fully polymeric electrode arrays for peripheral nerve stimulation, Advanced Science, Pages: 1-14, ISSN: 2198-3844
There is a critical need to transition research level flexible polymer bioelectronics toward the clinic by demonstrating both reliability in fabrication and stable device performance. Conductive elastomers (CEs) are composites of conductive polymers in elastomeric matrices that provide both flexibility and enhanced electrochemical properties compared to conventional metallic electrodes. This work focuses on the development of nerve cuff devices and the assessment of the device functionality at each development stage, from CE material to fully polymeric electrode arrays. Two device types are fabricated by laser machining of a thick and thin CE sheet variant on an insulative polydimethylsiloxane substrate and lamination into tubing to produce pre‐curled cuffs. Device performance and stability following sterilization and mechanical loading are compared to a state‐of‐the‐art stretchable metallic nerve cuff. The CE cuffs are found to be electrically and mechanically stable with improved charge transfer properties compared to the commercial cuff. All devices are applied to an ex vivo whole sciatic nerve and shown to be functional, with the CE cuffs demonstrating superior charge transfer and electrochemical safety in the biological environment.
Aregueta-Robles UA, Enke YL, Carter PM, et al., 2020, Subthreshold Electrical Stimulation for Controlling Protein-Mediated Impedance Increases in Platinum Cochlear Electrode, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 67, Pages: 3510-3520, ISSN: 0018-9294
Vallejo-Giraldo C, Genta M, Cauvi O, et al., 2020, Hydrogels for 3D neural tissue models: understanding cell-material interactions at a molecular level., Front Bioeng Biotechnol, Vol: 8, Pages: 1-14, ISSN: 2296-4185
The development of 3D neural tissue analogs is of great interest to a range of biomedical engineering applications including tissue engineering of neural interfaces, treatment of neurodegenerative diseases and in vitro assessment of cell-material interactions. Despite continued efforts to develop synthetic or biosynthetic hydrogels which promote the development of complex neural networks in 3D, successful long-term 3D approaches have been restricted to the use of biologically derived constructs. In this study a poly (vinyl alcohol) biosynthetic hydrogel functionalized with gelatin and sericin (PVA-SG), was used to understand the interplay between cell-cell communication and cell-material interaction. This was used to probe critical short-term interactions that determine the success or failure of neural network growth and ultimately the development of a useful model. Complex primary ventral mesencephalic (VM) neural cells were encapsulated in PVA-SG hydrogels and critical molecular cues that demonstrate mechanosensory interaction were examined. Neuronal presence was constant over the 10 day culture, but the astrocyte population decreased in number. The lack of astrocytic support led to a reduction in neural process outgrowth from 24.0 ± 1.3 μm on Day 7 to 7.0 ± 0.1 μm on Day 10. Subsequently, purified astrocytes were studied in isolation to understand the reasons behind PVA-SG hydrogel inability to support neural network development. It was proposed that the spatially restrictive nature (or tight mesh size) of PVA-SG hydrogels limited the astrocytic actin polymerization together with a cytoplasmic-nuclear translocation of YAP over time, causing an alteration in their cell cycle. This was confirmed by the evaluation of p27/Kip1 gene that was found to be upregulated by a twofold increase in expression at both Days 7 and 10 compared to Day 3, indicating the quiescent stage of the astrocytes in PVA-SG hydrogel. Cell migration was further studied by th
Novikov A, Goding J, Chapman C, et al., 2020, Stretchable bioelectronics: Mitigating the challenges of the percolation threshold in conductive elastomers, APL Materials, Vol: 8, Pages: 101105-101105
Dalrymple AN, Robles UA, Huynh M, et al., 2020, Electrochemical and biological performance of chronically stimulated conductive hydrogel electrodes, JOURNAL OF NEURAL ENGINEERING, Vol: 17, ISSN: 1741-2560
Dalrymple AN, Huynh M, Robles UA, et al., 2020, Electrochemical and mechanical performance of reduced graphene oxide, conductive hydrogel, and electrodeposited Pt-Ir coated electrodes: an active in vitro study, JOURNAL OF NEURAL ENGINEERING, Vol: 17, ISSN: 1741-2560
Chapman CAR, Cuttaz EA, Goding JA, et al., 2020, Actively controlled local drug delivery using conductive polymer-based devices, APPLIED PHYSICS LETTERS, Vol: 116, ISSN: 0003-6951
Aregueta-Robles UA, Martens PJ, Poole-Warren LA, et al., 2019, Tissue engineered hydrogels supporting 3D neural networks, Acta Biomaterialia, Vol: 95, Pages: 269-284, 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
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, Biomaterials Science, Vol: 7, Pages: 1372-1385, ISSN: 2047-4830
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.
Goding J, Vallejo-Giraldo C, Syed O, et 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.
Green R, 2019, Elastic and conductive hydrogel electrodes, NATURE BIOMEDICAL ENGINEERING, Vol: 3, Pages: 9-10, ISSN: 2157-846X
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: 1616-3028
© 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.
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: 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.
Staples NA, Goding JA, Gilmour AD, et al., 2018, Conductive hydrogel electrodes for delivery of long-term high frequency pulses, Frontiers in Neuroscience, Vol: 11, Pages: 1-13, 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.
© 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.
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: 2159-6867
© 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.
Goding J, Gilmour A, Martens P, et 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.
Palmer JC, Lord MS, Pinyon JL, et 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.
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
ï¿½ 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 ï¿½ 3 mV) compared to the Pt (317 ï¿½ 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.
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, 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.).
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, 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.
Hassarati RT, Marcal H, John L, et 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.
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., 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.
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
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