Invasive Intraneural Interfaces: Foreign Body Reaction Issues

Intraneural interfaces are stimulation/registration devices designed to couple the peripheral nervous system (PNS) with the environment. Over the last years, their use has increased in a wide range of applications, such as the control of a new generation of neural-interfaced prostheses. At present, the success of this technology is limited by an electrical impedance increase, due to an inflammatory response called foreign body reaction (FBR), which leads to the formation of a fibrotic tissue around the interface, eventually causing an inefficient transduction of the electrical signal. Based on recent developments in biomaterials and inflammatory/fibrotic pathologies, we explore and select the biological solutions that might be adopted in the neural interfaces FBR context: modifications of the interface surface, such as organic and synthetic coatings; the use of specific drugs or molecular biology tools to target the microenvironment around the interface; the development of bio-engineered-scaffold to reduce immune response and promote interface-tissue integration. By linking what we believe are the major crucial steps of the FBR process with related solutions, we point out the main issues that future research has to focus on: biocompatibility without losing signal conduction properties, good reproducible in vitro/in vivo models, drugs exhaustion and undesired side effects. The underlined pros and cons of proposed solutions show clearly the importance of a better understanding of all the molecular and cellular pathways involved and the need of a multi-target action based on a bio-engineered combination approach.

[1]  Christine E Schmidt,et al.  Nanostructured scaffolds for neural applications. , 2008, Nanomedicine.

[2]  Anna Kuchment The end of orange juice. , 2013, Scientific American.

[3]  David C. Martin,et al.  Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devices , 2008 .

[4]  J. Michel,et al.  Cell-free arterial grafts: morphologic characteristics of aortic isografts, allografts, and xenografts in rats. , 1994, Journal of vascular surgery.

[5]  Oliver Distler,et al.  Notch signalling regulates fibroblast activation and collagen release in systemic sclerosis , 2011, Annals of the rheumatic diseases.

[6]  Geny M. M. Groothuis,et al.  The Effect of Antifibrotic Drugs in Rat Precision-Cut Fibrotic Liver Slices , 2014, PloS one.

[7]  Benjamin G Keselowsky,et al.  Role of plasma fibronectin in the foreign body response to biomaterials. , 2007, Biomaterials.

[8]  D Kacy Cullen,et al.  Bionic connections. , 2013, Scientific American.

[9]  A Cutrone,et al.  Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes. , 2017, Biomaterials.

[10]  J. Ladero,et al.  Liver fibrosis. , 2018, The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology.

[11]  C. Waller,et al.  Imatinib mesylate. , 2010, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[12]  A. Atala,et al.  Tissue engineering using adult stem cells. , 2006, Methods in enzymology.

[13]  R V Bellamkonda,et al.  Bioimpedance modeling to monitor astrocytic response to chronically implanted electrodes , 2009, Journal of neural engineering.

[14]  P. Rossini,et al.  Double nerve intraneural interface implant on a human amputee for robotic hand control , 2010, Clinical Neurophysiology.

[15]  K. Horch,et al.  Object Discrimination With an Artificial Hand Using Electrical Stimulation of Peripheral Tactile and Proprioceptive Pathways With Intrafascicular Electrodes , 2011, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[16]  J. Hoffer,et al.  Chronically implanted epineural electrodes for repeated assessment of nerve conduction velocity and compound action potential amplitude in rodents , 2004, Journal of Neuroscience Methods.

[17]  John Powell,et al.  Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. , 2007, Arthritis and rheumatism.

[18]  Oliver Distler,et al.  Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis , 2012, Nature Communications.

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

[20]  Frank M Szaba,et al.  Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. , 2002, Blood.

[21]  Nigel H. Lovell,et al.  Organic electrode coatings for next-generation neural interfaces , 2014, Front. Neuroeng..

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

[23]  Daniel R. Merrill,et al.  Electrical stimulation of excitable tissue: design of efficacious and safe protocols , 2005, Journal of Neuroscience Methods.

[24]  Hiroaki Shimokawa,et al.  Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm. , 2003, Journal of the American College of Cardiology.

[25]  J W Eaton,et al.  Natural Responses to Unnatural Materials: A Molecular Mechanism for Foreign Body Reactions , 1999, Molecular medicine.

[26]  K. Horch,et al.  Effects of short-term training on sensory and motor function in severed nerves of long-term human amputees. , 2005, Journal of neurophysiology.

[27]  Andrew Wang,et al.  Targeting ADAM-17/notch signaling abrogates the development of systemic sclerosis in a murine model. , 2010, Arthritis and rheumatism.

[28]  D Kacy Cullen,et al.  Neural tissue engineering for neuroregeneration and biohybridized interface microsystems in vivo (Part 2). , 2011, Critical reviews in biomedical engineering.

[29]  N H Lovell,et al.  Performance of conducting polymer electrodes for stimulating neuroprosthetics , 2013, Journal of neural engineering.

[30]  S. Micera,et al.  A three-dimensional self-opening intraneural peripheral interface (SELINE) , 2015, Journal of neural engineering.

[31]  Hiroko Oshima,et al.  ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles , 2005, The Journal of cell biology.

[32]  Stéphanie P. Lacour,et al.  Flexible and stretchable micro-electrodes for in vitro and in vivo neural interfaces , 2010, Medical & Biological Engineering & Computing.

[33]  T. Stieglitz,et al.  A transverse intrafascicular multichannel electrode (TIME) to interface with the peripheral nerve. , 2010, Biosensors & bioelectronics.

[34]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[35]  E. Leof,et al.  The FASEB Journal • Research Communication Imatinib mesylate blocks a non-Smad TGF- � pathway and reduces renal fibrogenesis in vivo , 2022 .

[36]  Zhongyu Li,et al.  Effect of locally delivered IGF‐1 on nerve regeneration during aging: An experimental study in rats , 2010, Muscle & nerve.

[37]  Jochen Guck,et al.  The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system. , 2014, Biomaterials.

[38]  Christiana Ruhrberg,et al.  VEGF in the nervous system , 2010, Organogenesis.

[39]  Ken Yoshida,et al.  Assessment of Biocompatibility of Chronically Implanted Polyimide and Platinum Intrafascicular Electrodes , 2007, IEEE Transactions on Biomedical Engineering.

[40]  L. Zollo,et al.  Augmentation-related brain plasticity , 2014, Front. Syst. Neurosci..

[41]  Jessica A. Weber,et al.  The microRNA spectrum in 12 body fluids. , 2010, Clinical chemistry.

[42]  Thomas Stieglitz,et al.  Biocompatibility of Chronically Implanted Transverse Intrafascicular Multichannel Electrode (TIME) in the Rat Sciatic Nerve , 2011, IEEE Transactions on Biomedical Engineering.

[43]  Ajit S. Narang,et al.  Subcellular Fate and Off-Target Effects of siRNA, shRNA, and miRNA , 2011, Pharmaceutical Research.

[44]  Scott Bowes,et al.  Intracellular TGF-β Receptor Blockade Abrogates Smad-Dependent Fibroblast Activation In Vitro and In Vivo , 2006 .

[45]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[46]  Oliver Distler,et al.  Basic and translational research , 2011 .

[47]  W M Petroll,et al.  Inhibition of Corneal Fibrosis by Topical Application of Blocking Antibodies to TGFβ in the Rabbit , 1997, Cornea.

[48]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[49]  V. Koteliansky,et al.  Regulation of monocyte gene expression by the extracellular matrix and its functional implications , 2002, Immunological reviews.

[50]  D. Cho,et al.  3D printing of composite tissue with complex shape applied to ear regeneration , 2014, Biofabrication.

[51]  K. Leong,et al.  Scaffolding in tissue engineering: general approaches and tissue-specific considerations , 2008, European Spine Journal.

[52]  Antonio Frisoli,et al.  Grasping the Future: Advances in Powered Upper Limb Prosthetics , 2012 .

[53]  Ye Gan,et al.  Pirfenidone treatment of idiopathic pulmonary fibrosis , 2011, Therapeutics and clinical risk management.

[54]  Oliver Distler,et al.  Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis. , 2007, Arthritis and rheumatism.

[55]  Eva Syková,et al.  Diffusion barriers evoked in the rat cortex by reactive astrogliosis , 1999, Glia.

[56]  R L Schultz,et al.  The ultrastructure of the sheath around chronically implanted electrodes in brain , 1976, Journal of neurocytology.

[57]  Nigel H Lovell,et al.  Cell attachment functionality of bioactive conducting polymers for neural interfaces. , 2009, Biomaterials.

[58]  Khoon S Lim,et al.  Conductive hydrogels with tailored bioactivity for implantable electrode coatings. , 2014, Acta biomaterialia.

[59]  Paige Teller,et al.  The physiology of wound healing: injury through maturation. , 2009, The Surgical clinics of North America.

[60]  Yuko Fujihara,et al.  Immunological response to tissue-engineered cartilage derived from auricular chondrocytes and a PLLA scaffold in transgenic mice. , 2010, Biomaterials.

[61]  T L Babb,et al.  Tissue reactions to long-term electrical stimulation of the cerebellum in monkeys. , 1977, Journal of neurosurgery.

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

[63]  David Abraham,et al.  Systemic sclerosis: a prototypic multisystem fibrotic disorder. , 2007, The Journal of clinical investigation.

[64]  Buddy D Ratner,et al.  Biomaterials: where we have been and where we are going. , 2004, Annual review of biomedical engineering.

[65]  Patrick Aebischer,et al.  GDNF and NGF released by synthetic guidance channels support sciatic nerve regeneration across a long gap , 2002, The European journal of neuroscience.

[66]  Moon Suk Kim,et al.  An in vivo study of the host tissue response to subcutaneous implantation of PLGA- and/or porcine small intestinal submucosa-based scaffolds. , 2007, Biomaterials.

[67]  A. Kupsch,et al.  The effects of electrode material, charge density and stimulation duration on the safety of high-frequency stimulation of the subthalamic nucleus in rats , 2004, Journal of Neuroscience Methods.

[68]  Wen-Shiang Chen,et al.  Reducing the Foreign Body Reaction by Surface Modification with Collagen/Hyaluronic Acid Multilayered Films , 2014 .

[69]  Lei He,et al.  Electroactive SWNT/PEGDA hybrid hydrogel coating for bio-electrode interface. , 2011, Colloids and surfaces. B, Biointerfaces.

[70]  Eugenio Guglielmelli,et al.  Invasive neural interfaces: the perspective of the surgeon. , 2014, The Journal of surgical research.

[71]  S. Cowper,et al.  Nephrogenic systemic fibrosis: an overview. , 2008, Journal of the American College of Radiology : JACR.

[72]  Suwan N Jayasinghe,et al.  Living scaffolds (specialized and unspecialized) for regenerative and therapeutic medicine. , 2008, Biomacromolecules.

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

[74]  Eduardo Fernández,et al.  Long-term stimulation and recording with a penetrating microelectrode array in cat sciatic nerve , 2004, IEEE Transactions on Biomedical Engineering.

[75]  R. Diegelmann,et al.  Wound healing: an overview of acute, fibrotic and delayed healing. , 2004, Frontiers in bioscience : a journal and virtual library.

[76]  M. Alcaide,et al.  Boron-Doped Nanocrystalline Diamond Electrodes for Neural Interfaces: In vivo Biocompatibility Evaluation , 2016, Front. Neurosci..

[77]  David P Lerner,et al.  Focal neuronal dysfunction resulting in subclinical status epilepticus in von gierke's disease , 2015, The International journal of neuroscience.

[78]  G. Wallace,et al.  Conducting polymers for neural interfaces: challenges in developing an effective long-term implant. , 2008, Biomaterials.

[79]  David Nilsson,et al.  Active Control of Epithelial Cell‐Density Gradients Grown Along the Channel of an Organic Electrochemical Transistor , 2009, Advanced materials.

[80]  Srinivas Madduri,et al.  Effect of controlled co-delivery of synergistic neurotrophic factors on early nerve regeneration in rats. , 2010, Biomaterials.

[81]  S. Willerth,et al.  Approaches to neural tissue engineering using scaffolds for drug delivery. , 2007, Advanced drug delivery reviews.

[82]  André Mercanzini,et al.  Controlled release nanoparticle-embedded coatings reduce the tissue reaction to neuroprostheses. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[83]  Jesús Prieto,et al.  Topical application of a peptide inhibitor of transforming growth factor-beta1 ameliorates bleomycin-induced skin fibrosis. , 2005, The Journal of investigative dermatology.

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

[85]  Lianbo Yu,et al.  Detection of microRNA Expression in Human Peripheral Blood Microvesicles , 2008, PloS one.

[86]  Charles L. Cooney,et al.  Lessons from innovation in drug-device combination products. , 2011, Advanced drug delivery reviews.

[87]  D. K. Cullen,et al.  Neural tissue engineering and biohybridized microsystems for neurobiological investigation in vitro (Part 1). , 2011, Critical reviews in biomedical engineering.

[88]  E. Hol,et al.  Cell-replacement and gene-therapy strategies for Parkinson's and Alzheimer's disease. , 2007, Regenerative medicine.

[89]  Gaelle Lissorgues,et al.  3D-nanostructured boron-doped diamond for microelectrode array neural interfacing. , 2015, Biomaterials.

[90]  M. Jinnin,et al.  Characterization of SIS3, a Novel Specific Inhibitor of Smad3, and Its Effect on Transforming Growth Factor-β1-Induced Extracellular Matrix Expression , 2006, Molecular Pharmacology.

[91]  J M Anderson,et al.  Inflammatory response to implants. , 1988, ASAIO transactions.

[92]  Marleen Welkenhuysen,et al.  Histological Alterations Induced by Electrode Implantation and Electrical Stimulation in the Human Brain: A Review , 2007, Neuromodulation : journal of the International Neuromodulation Society.

[93]  Nick F. Ramsey,et al.  Physiological Challenges for Intracortical Electrodes , 2014, Brain Stimulation.

[94]  S. Wong,et al.  MicroRNA-mediated immune modulation as a therapeutic strategy in host-implant integration. , 2015, Advanced drug delivery reviews.

[95]  Kevin J. Otto,et al.  In vivo polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in rodent cerebral cortex , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[96]  S Gilman,et al.  Long-term surface stimulation of the cerebellum in the monkey. II. Electron microscopic and biochemical observations. , 1977, Surgical neurology.

[97]  X Liu,et al.  Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes. , 1999, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[98]  James M. Anderson,et al.  Multinucleated giant cells , 2000, Current opinion in hematology.

[99]  Vineeth Rajkumar,et al.  New developments in fibroblast and myofibroblast biology: Implications for fibrosis and scleroderma , 2007, Current rheumatology reports.

[100]  Shaoyi Jiang,et al.  Zwitterionic hydrogels implanted in mice resist the foreign-body reaction , 2013, Nature Biotechnology.

[101]  Fan Yang,et al.  The future of biologic coatings for orthopaedic implants. , 2013, Biomaterials.

[102]  N. Lago,et al.  Long term assessment of axonal regeneration through polyimide regenerative electrodes to interface the peripheral nerve. , 2005, Biomaterials.

[103]  Gordon G Wallace,et al.  Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes. , 2009, Journal of biomedical materials research. Part A.

[104]  Oliver Distler,et al.  Rho-associated kinases are crucial for myofibroblast differentiation and production of extracellular matrix in scleroderma fibroblasts. , 2008, Arthritis and rheumatism.

[105]  Hiroaki Takehara,et al.  Lab-on-a-brain: Implantable micro-optical fluidic devices for neural cell analysis in vivo , 2014, Scientific Reports.

[106]  David Abraham,et al.  Fibrosis in connective tissue disease: the role of the myofibroblast and fibroblast-epithelial cell interactions , 2007, Arthritis research & therapy.

[107]  Seeram Ramakrishna,et al.  Applications of conducting polymers and their issues in biomedical engineering , 2010, Journal of The Royal Society Interface.

[108]  Bulent Ozpolat,et al.  Preclinical and clinical development of siRNA-based therapeutics. , 2015, Advanced drug delivery reviews.

[109]  Tsutomu Masaki,et al.  Imatinib mesylate (STI-571) attenuates liver fibrosis development in rats. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[110]  Krasimir Vasilev,et al.  Innate Immunity and Biomaterials at the Nexus: Friends or Foes , 2015, BioMed research international.

[111]  Kevin Warwick,et al.  The application of implant technology for cybernetic systems. , 2003, Archives of neurology.

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

[113]  Silvestro Micera,et al.  A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems , 2005, Journal of the peripheral nervous system : JPNS.

[114]  Xavier Navarro,et al.  Neurobiological Assessment of Regenerative Electrodes for Bidirectional Interfacing Injured Peripheral Nerves , 2007, IEEE Transactions on Biomedical Engineering.

[115]  Anne J. Ridley,et al.  ROCKs: multifunctional kinases in cell behaviour , 2003, Nature Reviews Molecular Cell Biology.

[116]  David C. Martin,et al.  In vivo studies of polypyrrole/peptide coated neural probes. , 2003, Biomaterials.

[117]  S. Micera,et al.  Intrafascicular thin-film multichannel electrodes for sensory feedback: Evidences on a human amputee , 2010, 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology.

[118]  M. Hincke,et al.  Fibrin: a versatile scaffold for tissue engineering applications. , 2008, Tissue engineering. Part B, Reviews.

[119]  N. Bottini,et al.  Multi-walled carbon nanotubes induce T lymphocyte apoptosis. , 2006, Toxicology letters.

[120]  Min Hyun Cho,et al.  Renal fibrosis , 2010, Korean journal of pediatrics.

[121]  L. Geddes,et al.  Criteria for the Selection of Materials for Implanted Electrodes , 2003, Annals of Biomedical Engineering.

[122]  William Shain,et al.  Effects of Glial Cells on Electrode Impedance Recorded from Neural Prosthetic Devices In Vitro , 2010, Annals of Biomedical Engineering.

[123]  Yael Hanein,et al.  All-carbon-nanotube flexible multi-electrode array for neuronal recording and stimulation , 2014, Biomedical microdevices.

[124]  F. Hambrecht,et al.  CRITERIA FOR SELECTING ELECTRODES FOR ELECTRICAL STIMULATION: THEORETICAL AND PRACTICAL CONSIDERATIONS , 1983, Annals of the New York Academy of Sciences.

[125]  Mark Huang,et al.  Advances in amputee care. , 2006, Archives of physical medicine and rehabilitation.

[126]  Winnie Jensen,et al.  Stimulation Selectivity of the “Thin-Film Longitudinal Intrafascicular Electrode” (tfLIFE) and the “Transverse Intrafascicular Multi-Channel Electrode” (TIME) in the Large Nerve Animal Model , 2014, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[127]  Matthew D. Johnson,et al.  In vivo impedance spectroscopy of deep brain stimulation electrodes , 2009, Journal of neural engineering.

[128]  Scott Bowes,et al.  Intracellular TGF-beta receptor blockade abrogates Smad-dependent fibroblast activation in vitro and in vivo. , 2006, The Journal of investigative dermatology.

[129]  Clayton J. Underwood,et al.  Characterization of microglial attachment and cytokine release on biomaterials of differing surface chemistry. , 2008, Biomaterials.

[130]  Wenjing Hu,et al.  Surface chemistry influences implant biocompatibility. , 2008, Current topics in medicinal chemistry.

[131]  Paolo Maria Rossini,et al.  Neuroplasticity in amputees: Main implications on bidirectional interfacing of cybernetic hand prostheses , 2009, Progress in Neurobiology.

[132]  C. Daniels,et al.  Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. , 2004, The Journal of clinical investigation.

[133]  Ronald V Maier,et al.  Effects of adsorbed proteins and surface chemistry on foreign body giant cell formation, tumor necrosis factor alpha release and procoagulant activity of monocytes. , 2004, Journal of biomedical materials research. Part A.

[134]  Yixia Yin,et al.  Use new PLGL-RGD-NGF nerve conduits for promoting peripheral nerve regeneration , 2012, BioMedical Engineering OnLine.

[135]  J. Michel,et al.  The immunogenicity of the extracellular matrix in arterial xenografts. , 1997, Surgery.

[136]  J. Rosenbloom,et al.  Strategies for anti-fibrotic therapies. , 2013, Biochimica et biophysica acta.

[137]  Oliver Distler,et al.  Treatment with imatinib prevents fibrosis in different preclinical models of systemic sclerosis and induces regression of established fibrosis. , 2009, Arthritis and rheumatism.

[138]  J T Mortimer,et al.  Stability of the input-output properties of chronically implanted multiple contact nerve cuff stimulating electrodes. , 1998, IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society.

[139]  Nicholas B Langhals,et al.  Regenerative Electrode Interfaces for Neural Prostheses. , 2016, Tissue engineering. Part B, Reviews.

[140]  Melba Navarro,et al.  Impact of 3-D printed PLA- and chitosan-based scaffolds on human monocyte/macrophage responses: unraveling the effect of 3-D structures on inflammation. , 2014, Acta biomaterialia.

[141]  Benjamin M Wu,et al.  A three-dimensional in vitro model to quantify inflammatory response to biomaterials. , 2014, Acta biomaterialia.

[142]  S Gilman,et al.  Long-term surface stimulation of the cerebellum in the monkey. I. Light microscopic, electrophysiologic, and clinical observations. , 1977, Surgical neurology.

[143]  Luca Citi,et al.  Restoring Natural Sensory Feedback in Real-Time Bidirectional Hand Prostheses , 2014, Science Translational Medicine.

[144]  Daryl R. Kipke,et al.  Conducting-polymer nanotubes improve electrical properties, mechanical adhesion, neural attachment, and neurite outgrowth of neural electrodes. , 2010, Small.

[145]  J. Thomas Mortimer,et al.  Recruitment properties of monopolar and bipolar epimysial electrodes , 2006, Annals of Biomedical Engineering.

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

[147]  K. Yoshida,et al.  Selective stimulation of peripheral nerve fibers using dual intrafascicular electrodes , 1993, IEEE Transactions on Biomedical Engineering.

[148]  K. Horch,et al.  Acute peripheral nerve recording Characteristics of polymer-based longitudinal intrafascicular electrodes , 2004, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[149]  Alberto Mantovani,et al.  Macrophage plasticity and polarization: in vivo veritas. , 2012, The Journal of clinical investigation.

[150]  Yong Wang,et al.  Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates , 2015, Nature materials.

[151]  Christine E Schmidt,et al.  Cell-laden hydrogel constructs of hyaluronic acid, collagen, and laminin for neural tissue engineering. , 2010, Tissue engineering. Part A.

[152]  D. K. Cullen,et al.  Restoring nervous system structure and function using tissue engineered living scaffolds , 2015, Neural regeneration research.

[153]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[154]  S. Micera,et al.  In Human Implant of Intraneural Multielectrodes for Controlling a 5-Fingered Hand Prosthesis and Delivering Sensorial Feedback , 2012 .

[155]  M. Kennett,et al.  Use of a TGFbeta type I receptor inhibitor in mouse skin carcinogenesis reveals a dual role for TGFbeta signaling in tumor promotion and progression. , 2010, Carcinogenesis.

[156]  Craig T. Nordhausen,et al.  Single unit recording capabilities of a 100 microelectrode array , 1996, Brain Research.

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

[158]  H. Schwarz,et al.  Cytotoxicity of single-wall carbon nanotubes on human fibroblasts. , 2006, Toxicology in vitro : an international journal published in association with BIBRA.

[159]  C. McIntyre,et al.  Sources and effects of electrode impedance during deep brain stimulation , 2006, Clinical Neurophysiology.

[160]  S. V. van Putten,et al.  The downmodulation of the foreign body reaction by cytomegalovirus encoded interleukin-10. , 2009, Biomaterials.

[161]  Winnie Jensen,et al.  Subchronic stimulation performance of transverse intrafascicular multichannel electrodes in the median nerve of the Göttingen minipig. , 2015, Artificial organs.

[162]  James M. Anderson,et al.  Foreign body reaction to biomaterials. , 2008, Seminars in immunology.

[163]  Ravi S Kane,et al.  The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells. , 2009, Biomaterials.

[164]  David W Grainger,et al.  Device-based local delivery of siRNA against mammalian target of rapamycin (mTOR) in a murine subcutaneous implant model to inhibit fibrous encapsulation. , 2010, Journal of controlled release : official journal of the Controlled Release Society.