Mechanically adaptive nanocomposites for neural interfacing

The recording of neural signals with microelectrodes that are implanted into the cortex of the brain is potentially useful for a range of clinical applications. However, the widespread use of such neural interfaces has so far been stifled because existing intracortical electrode systems rarely allow for consistent long-term recording of neural activity. This limitation is usually attributed to scar formation and neuron death near the surface of the implanted electrode. It has been proposed that the mechanical property mismatch between existing electrode materials and the brain tissue is a significant contributor to these events. To alleviate this problem, we utilized the architecture of the sea cucumber dermis as a blueprint to engineer a new class of mechanically adaptive materials as substrates for “smart” intracortical electrodes. We demonstrated that these originally rigid polymer nanocomposites soften considerably upon exposure to emulated physiological and in vivo conditions. The adaptive nature of these bioinspired materials makes them useful as a basis for electrodes that are sufficiently stiff to be easily implanted and subsequently soften to better match the stiffness of the brain. Initial histological evaluations suggest that mechanically adaptive neural prosthetics can more rapidly stabilize neural cell populations at the device interface than rigid systems, which bodes well for improving the functionality of intracortical devices.

[1]  S. Retterer,et al.  Dexamethasone treatment reduces astroglia responses to inserted neuroprosthetic devices in rat neocortex , 2005, Experimental Neurology.

[2]  John R. Reynolds,et al.  Electrochemical polymerization of poly(hydroxymethylated-3,4-ethylenedioxythiophene) (PEDOT-MeOH) on multichannel neural probes , 2004 .

[3]  Kentaro Abe,et al.  Review: current international research into cellulose nanofibres and nanocomposites , 2010, Journal of Materials Science.

[4]  Stuart J. Rowan,et al.  Biomimetic mechanically adaptive nanocomposites , 2010 .

[5]  Karen L. Smith,et al.  Ultrafast resorbing polymers for use as carriers for cortical neural probes. , 2011, Acta biomaterialia.

[6]  Patrick A Tresco,et al.  The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull. , 2007, Journal of biomedical materials research. Part A.

[7]  D. Kipke,et al.  Neural probe design for reduced tissue encapsulation in CNS. , 2007, Biomaterials.

[8]  Andrew S. Whitford,et al.  Cortical control of a prosthetic arm for self-feeding , 2008, Nature.

[9]  J. Hetke,et al.  Surface modification of neural recording electrodes with conducting polymer/biomolecule blends. , 2001, Journal of biomedical materials research.

[10]  S. Rowan,et al.  Stimuli-responsive, mechanically-adaptive polymer nanocomposites , 2011 .

[11]  Matthew D. Johnson,et al.  Spatiotemporal pH dynamics following insertion of neural microelectrode arrays , 2007, Journal of Neuroscience Methods.

[12]  D. Tyler,et al.  Stimuli-Responsive Polymer Nanocomposites Inspired by the Sea Cucumber Dermis , 2008, Science.

[13]  James P. Harris,et al.  In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes , 2011, Journal of neural engineering.

[14]  X. Cui,et al.  Poly (3,4-Ethylenedioxythiophene) for Chronic Neural Stimulation , 2007, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[15]  R. Bellamkonda,et al.  Biomechanical analysis of silicon microelectrode-induced strain in the brain , 2005, Journal of neural engineering.

[16]  I. Wilkie Is muscle involved in the mechanical adaptability of echinoderm mutable collagenous tissue? , 2002, The Journal of experimental biology.

[17]  Patrick A Tresco,et al.  Chronic response of adult rat brain tissue to implants anchored to the skull. , 2004, Biomaterials.

[18]  Christoph Weder,et al.  Development of a stimuli-responsive polymer nanocomposite toward biologically optimized, MEMS-based neural probes , 2011 .

[19]  S. Retterer,et al.  Controlling cellular reactive responses around neural prosthetic devices using peripheral and local intervention strategies , 2003, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[20]  Lynn A. Capadona,et al.  A versatile approach for the processing of polymer nanocomposites with self-assembled nanofibre templates. , 2007, Nature nanotechnology.

[21]  Stuart J. Rowan,et al.  Bioinspired Mechanically Adaptive Polymer Nanocomposites with Water-Activated Shape-Memory Effect , 2011 .

[22]  Miguel A. L. Nicolelis,et al.  Brain–machine interfaces: past, present and future , 2006, Trends in Neurosciences.

[23]  J. Muthuswamy,et al.  Brain micromotion around implants in the rodent somatosensory cortex , 2006, Journal of neural engineering.

[24]  Trotter,et al.  Cell-derived stiffening and plasticizing factors in sea cucumber (Cucumaria frondosa) dermis , 1999, The Journal of experimental biology.

[25]  C. Weder,et al.  Solid polymer electrolytes based on nanocomposites of ethylene oxide–epichlorohydrin copolymers and cellulose whiskers , 2004 .

[26]  Justin C. Williams,et al.  Flexible polyimide-based intracortical electrode arrays with bioactive capability , 2001, IEEE Transactions on Biomedical Engineering.

[27]  D. Loane,et al.  Role of microglia in neurotrauma , 2010, Neurotherapeutics.

[28]  R. Shadwick,et al.  Dynamic mechanical characterization of a mutable collagenous tissue: response of sea cucumber dermis to cell lysis and dermal extracts. , 2000, The Journal of experimental biology.

[29]  P. Tresco,et al.  The challenge of integrating devices into the central nervous system. , 2011, Critical reviews in biomedical engineering.

[30]  Karen L. Smith,et al.  Effects of insertion conditions on tissue strain and vascular damage during neuroprosthetic device insertion , 2006, Journal of neural engineering.

[31]  D. Szarowski,et al.  Brain responses to micro-machined silicon devices , 2003, Brain Research.

[32]  Shashi K. Murthy,et al.  Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology , 2009, Front. Neuroeng..

[33]  Rosa Villa,et al.  Study of functional viability of SU-8-based microneedles for neural applications , 2009 .

[34]  S. Eichhorn,et al.  Stress transfer in cellulose nanowhisker composites--influence of whisker aspect ratio and surface charge. , 2011, Biomacromolecules.

[35]  M. Takayanagi,et al.  Application of equivalent model method to dynamic rheo‐optical properties of crystalline polymer , 2007 .

[36]  Daryl R. Kipke,et al.  The role of flexible polymer interconnects in chronic tissue response induced by intracortical microelectrodes - a modeling and an in vivo study , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[37]  Yuliang Cao,et al.  Poly(vinyl alcohol)/poly(acrylic acid) hydrogel coatings for improving electrode-neural tissue interface. , 2009, Biomaterials.

[38]  W. Reichert Indwelling Neural Implants : Strategies for Contending with the In Vivo Environment , 2007 .

[39]  Stuart J. Rowan,et al.  Stimuli-responsive mechanically adaptive polymer nanocomposites. , 2010, ACS applied materials & interfaces.

[40]  Jon A. Mukand,et al.  Neuronal ensemble control of prosthetic devices by a human with tetraplegia , 2006, Nature.

[41]  David C. Martin,et al.  Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery. , 2006, Biomaterials.

[42]  Christoph Weder,et al.  Polymer nanocomposites with nanowhiskers isolated from microcrystalline cellulose. , 2009, Biomacromolecules.

[43]  K. Mabuchi,et al.  3D flexible multichannel neural probe array , 2004 .

[44]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[45]  Stephen J. Eichhorn,et al.  An estimation of the Young’s modulus of bacterial cellulose filaments , 2008 .

[46]  Jiping He,et al.  Polyimide-based intracortical neural implant with improved structural stiffness , 2004 .

[47]  Stuart J. Rowan,et al.  Bio-inspired mechanically-adaptive nanocomposites derived from cotton cellulose whiskers , 2010 .

[48]  Jiping He,et al.  Polyimide based neural implants with stiffness improvement , 2004 .

[49]  Trotter,et al.  Evidence that calcium-dependent cellular processes are involved in the stiffening response of holothurian dermis and that dermal cells contain an organic stiffening factor , 1995, The Journal of experimental biology.

[50]  John P. Donoghue,et al.  Bridging the Brain to the World: A Perspective on Neural Interface Systems , 2008, Neuron.

[51]  S. Eichhorn,et al.  Determination of the stiffness of cellulose nanowhiskers and the fiber-matrix interface in a nanocomposite using Raman spectroscopy , 2008 .

[52]  Xinyan Tracy Cui,et al.  Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[53]  E. Fetz,et al.  Direct control of paralyzed muscles by cortical neurons , 2008, Nature.

[54]  David C. Martin,et al.  Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4-ethylenedioxythiophene) (PEDOT) film , 2006, Journal of neural engineering.

[55]  Ravi V. Bellamkonda,et al.  A Novel Anti‐inflammatory Surface for Neural Electrodes , 2007 .

[56]  B A Wester,et al.  Development and characterization of in vivo flexible electrodes compatible with large tissue displacements , 2009, Journal of neural engineering.

[57]  Christoph Weder,et al.  Stress-transfer in anisotropic and environmentally adaptive cellulose whisker nanocomposites. , 2010, Biomacromolecules.

[58]  J. Trotter,et al.  Towards a fibrous composite with dynamically controlled stiffness: lessons from echinoderms. , 2000, Biochemical Society transactions.

[59]  Ken Gall,et al.  Toward a self-deploying shape memory polymer neuronal electrode , 2006, Journal of neural engineering.

[60]  Philippe Renaud,et al.  In Vivo Electrical Impedance Spectroscopy of Tissue Reaction to Microelectrode Arrays , 2009, IEEE Transactions on Biomedical Engineering.

[61]  D. Kipke,et al.  Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain , 2009, Journal of Neuroscience Methods.

[62]  Jochen Guck,et al.  Viscoelastic properties of individual glial cells and neurons in the CNS , 2006, Proceedings of the National Academy of Sciences.

[63]  David C. Martin,et al.  Conducting polymers grown in hydrogel scaffolds coated on neural prosthetic devices. , 2004, Journal of biomedical materials research. Part A.

[64]  G. Buzsáki Large-scale recording of neuronal ensembles , 2004, Nature Neuroscience.

[65]  David C. Martin,et al.  Electrochemical deposition and characterization of poly(3,4-ethylenedioxythiophene) on neural microelectrode arrays , 2003 .

[66]  R. Bellamkonda,et al.  Biomaterials for the central nervous system , 2008, Journal of The Royal Society Interface.

[67]  J Miller,et al.  Minocycline increases quality and longevity of chronic neural recordings , 2007, Journal of neural engineering.

[68]  Jean-Marc Fellous,et al.  In vitro model of glial scarring around neuroelectrodes chronically implanted in the CNS. , 2006, Biomaterials.

[69]  Ravi V. Bellamkonda,et al.  Dexamethasone-coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes , 2007, Brain Research.

[70]  S. Eichhorn,et al.  Elastic modulus and stress-transfer properties of tunicate cellulose whiskers. , 2005, Biomacromolecules.

[71]  Andrew B. Schwartz,et al.  Brain-Controlled Interfaces: Movement Restoration with Neural Prosthetics , 2006, Neuron.

[72]  Jiping He,et al.  Benzocyclobutene (BCB) based intracortical neural implant , 2003, Proceedings International Conference on MEMS, NANO and Smart Systems.

[73]  David C. Martin,et al.  Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays , 2005, Experimental Neurology.

[74]  Miguel A. L. Nicolelis,et al.  Actions from thoughts , 2001, Nature.

[75]  J. Wolpaw,et al.  Brain–computer interfaces in neurological rehabilitation , 2008, The Lancet Neurology.

[76]  James P. Harris,et al.  Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies , 2011, Journal of neural engineering.

[77]  Daryl R Kipke,et al.  Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants , 2007, Journal of neural engineering.

[78]  Jiping He,et al.  Biocompatible benzocyclobutene (BCB)-based neural implants with micro-fluidic channel. , 2004, Biosensors & bioelectronics.

[79]  A. Levey,et al.  Implanted neural electrodes cause chronic, local inflammation that is correlated with local neurodegeneration , 2009, Journal of neural engineering.

[80]  M. Ward,et al.  Toward a comparison of microelectrodes for acute and chronic recordings , 2009, Brain Research.

[81]  K. Mabuchi,et al.  Parylene flexible neural probes integrated with microfluidic channels. , 2005, Lab on a chip.

[82]  Andrew B Schwartz,et al.  Cortical neural prosthetics. , 2004, Annual review of neuroscience.

[83]  Ravi V. Bellamkonda,et al.  Extraction Force and Cortical Tissue Reaction of Silicon Microelectrode Arrays Implanted in the Rat Brain , 2007, IEEE Transactions on Biomedical Engineering.

[84]  David C. Martin,et al.  Surface modification of neural probes with conducting polymer poly(hydroxymethylated-3,4-ethylenedioxythiophene) and its biocompatibility , 2006, Applied biochemistry and biotechnology.

[85]  H. Schiöth,et al.  Alpha-Melanocyte-Stimulating Hormone through Melanocortin-4 Receptor Inhibits Nitric Oxide Synthase and Cyclooxygenase Expression in the Hypothalamus of Male Rats , 2004, Neuroendocrinology.

[86]  J. Capadona,et al.  Preparation of homogeneous dispersions of tunicate cellulose whiskers in organic solvents. , 2007, Biomacromolecules.

[87]  David J. Anderson,et al.  Electrochemical deposition and characterization of conducting polymer polypyrrole/PSS on multichannel neural probes , 2001 .

[88]  David C. Martin,et al.  A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex , 2005, Journal of neural engineering.