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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Long-term implantable neural electrodes underpin brain\u2013machine interfaces, deep brain stimulation, epilepsy monitoring, and closed-loop neuromodulation. Following chronic implantation, however, the foreign body response (FBR) at the electrode\u2013tissue interface remains a major constraint on long-term performance, as reflected by increased interfacial impedance, lower signal-to-noise ratios, fewer resolvable units, and higher stimulation thresholds. This deterioration arises from interrelated events that include implantation injury, protein adsorption, blood\u2013brain barrier disruption, complement activation, glial reactivity, oxidative stress, glial scar formation, and neuronal loss. It cannot be attributed solely to material ageing or encapsulation failure. This review examines the molecular mechanisms of neural-electrode FBR and relates them to surface-biofunctionalization strategies, including antifouling coatings, bioactive ligands, immobilized neurotrophic factors, drug-eluting electrodes, and emerging immunomodulatory interfaces. Establishing mechanistic links among molecular events, material interfaces, and functionalization strategies may guide the rational design of durable neural electrodes.<\/jats:p>","DOI":"10.3390\/ijms27156752","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:07:33Z","timestamp":1785244053000},"page":"6752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanisms of Foreign Body Responses to Neural Electrodes and Surface Biofunctionalization Strategies for Interface Modulation"],"prefix":"10.3390","volume":"27","author":[{"given":"Ziliang","family":"He","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Faculty of Life and Health Sciences, Shenzhen University of Advanced Technology (SUAT), Shenzhen 518107, China"},{"name":"Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlong","family":"Ma","sequence":"additional","affiliation":[{"name":"Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS), Shenzhen 518055, China"},{"name":"The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"Jiangsu Brain-Computer Interface Research Institute, Nanjing 210033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"Jiangsu Brain-Computer Interface Research Institute, Nanjing 210033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6535-1424","authenticated-orcid":false,"given":"Zhanhong","family":"Du","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"Jiangsu Brain-Computer Interface Research Institute, Nanjing 210033, China"},{"name":"Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev.bioeng.10.061807.160518","article-title":"Neural Stimulation and Recording Electrodes","volume":"10","author":"Cogan","year":"2008","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1021\/cn500256e","article-title":"Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies","volume":"6","author":"Kozai","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1126\/science.1260318","article-title":"Electronic dura mater for long-term multimodal neural interfaces","volume":"347","author":"Minev","year":"2015","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1109\/TNSRE.2003.814443","article-title":"Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex","volume":"11","author":"Kipke","year":"2003","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1523\/JNEUROSCI.2339-15.2016","article-title":"Long-Term Stability of Motor Cortical Activity: Implications for Brain Machine Interfaces and Optimal Feedback Control","volume":"36","author":"Flint","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"066014","DOI":"10.1088\/1741-2560\/10\/6\/066014","article-title":"Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates","volume":"10","author":"Barrese","year":"2013","journal-title":"J. Neural Eng."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10742","DOI":"10.1523\/JNEUROSCI.0959-07.2007","article-title":"Single-Neuron Stability during Repeated Reaching in Macaque Premotor Cortex","volume":"27","author":"Chestek","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brs.2013.07.001","article-title":"Physiological Challenges for Intracortical Electrodes","volume":"7","author":"Groothuis","year":"2014","journal-title":"Brain Stimul."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"046010","DOI":"10.1088\/1741-2560\/11\/4\/046010","article-title":"Analysis of deep brain stimulation electrode characteristics for neural recording","volume":"11","author":"Kent","year":"2014","journal-title":"J. Neural Eng."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"025001","DOI":"10.1088\/1741-2552\/abd897","article-title":"Understanding charge transfer on the clinically used conical Utah electrode array: Charge storage capacity, electrochemical impedance spectroscopy and effective electrode area","volume":"18","author":"Harris","year":"2021","journal-title":"J. Neural Eng."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Campbell, A., and Wu, C. (2018). Chronically Implanted Intracranial Electrodes: Tissue Reaction and Electrical Changes. Micromachines, 9.","DOI":"10.3390\/mi9090430"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4958","DOI":"10.1039\/D3MA01105D","article-title":"The past, present, and future of in vivo-implantable recording microelectrodes: The neural interfaces","volume":"5","author":"Liu","year":"2024","journal-title":"Mater. Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.expneurol.2005.04.020","article-title":"Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays","volume":"195","author":"Biran","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cobme.2017.09.003","article-title":"Recent advances in neural electrode\u2013tissue interfaces","volume":"4","author":"Woeppel","year":"2017","journal-title":"Curr. Opin. Biomed. Eng."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"026007","DOI":"10.1088\/1741-2560\/10\/2\/026007","article-title":"Chronic intracortical microelectrode arrays induce non-uniform, depth-related tissue responses","volume":"10","author":"Woolley","year":"2013","journal-title":"J. Neural Eng."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"016019","DOI":"10.1088\/1741-2560\/12\/1\/016019","article-title":"Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord","volume":"12","author":"Ersen","year":"2015","journal-title":"J. Neural Eng."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1016\/j.biomaterials.2013.03.007","article-title":"The impact of chronic blood\u2013brain barrier breach on intracortical electrode function","volume":"34","author":"Saxena","year":"2013","journal-title":"Biomaterials"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0006-8993(03)03023-3","article-title":"Brain responses to micro-machined silicon devices","volume":"983","author":"Szarowski","year":"2003","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.smim.2007.11.004","article-title":"Foreign body reaction to biomaterials","volume":"20","author":"Anderson","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"016013","DOI":"10.1088\/1741-2560\/10\/1\/016013","article-title":"Nanoparticle-based evaluation of blood\u2013brain barrier leakage during the foreign body response","volume":"10","author":"Sawyer","year":"2013","journal-title":"J. Neural Eng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"046033","DOI":"10.1088\/1741-2552\/ad5936","article-title":"Spatial transcriptomics at the brain-electrode interface in rat motor cortex and the relationship to recording quality","volume":"21","author":"Whitsitt","year":"2024","journal-title":"J. Neural Eng."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/jbm.a.31138","article-title":"The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull","volume":"82","author":"Biran","year":"2007","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1088\/1741-2560\/3\/3\/001","article-title":"Brain micromotion around implants in the rodent somatosensory cortex","volume":"3","author":"Gilletti","year":"2006","journal-title":"J. Neural Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneumeth.2005.08.015","article-title":"Response of brain tissue to chronically implanted neural electrodes","volume":"148","author":"Polikov","year":"2005","journal-title":"J. Neurosci. Methods"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chakraborty, A., Purcell, E.K., and Moore, M.G. (2025). DiffCoRank: A comprehensive framework for discovering hub genes and differential gene co-expression in brain implant-associated tissue responses. BMC Bioinform., 26.","DOI":"10.1186\/s12859-025-06232-y"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1557\/s43577-023-00530-7","article-title":"Advanced in vivo fluorescence microscopy of neural electronic interface","volume":"48","author":"Yang","year":"2023","journal-title":"MRS Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"066001","DOI":"10.1088\/1741-2560\/9\/6\/066001","article-title":"In vivo two-photon microscopy reveals immediate microglial reaction to implantation of microelectrode through extension of processes","volume":"9","author":"Kozai","year":"2012","journal-title":"J. Neural Eng."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1002\/jbm.a.35958","article-title":"The pathology of the foreign body reaction against biomaterials","volume":"105","author":"Klopfleisch","year":"2017","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"376a","DOI":"10.1016\/j.bpj.2012.11.2092","article-title":"Is the Extent of Blood-Brain-Barrier Breach Predictive of Intracortical Electrode Performance?","volume":"104","author":"Bellamkonda","year":"2013","journal-title":"Biophys. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev-neuro-061010-113810","article-title":"The Complement System: An Unexpected Role in Synaptic Pruning During Development and Disease","volume":"35","author":"Stephan","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1126\/science.aad8373","article-title":"Complement and microglia mediate early synapse loss in Alzheimer mouse models","volume":"352","author":"Hong","year":"2016","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1126\/science.1110647","article-title":"Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma In Vivo","volume":"308","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/nn1997","article-title":"Microglia: Active sensor and versatile effector cells in the normal and pathologic brain","volume":"10","author":"Hanisch","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: A field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrn2038","article-title":"Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms","volume":"8","author":"Block","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nature11729","article-title":"NLRP3 is activated in Alzheimer\u2019s disease and contributes to pathology in APP\/PS1 mice","volume":"493","author":"Heneka","year":"2013","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The Inflammasome","volume":"10","author":"Martinon","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Krahe, D.D., Woeppel, K.M., Yang, Q., Kushwah, N., and Cui, X.T. (2022). Melatonin Decreases Acute Inflammatory Response to Neural Probe Insertion. Antioxidants, 11.","DOI":"10.20944\/preprints202207.0258.v1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.nurt.2010.07.003","article-title":"Reactive Astrocytes as Therapeutic Targets for CNS Disorders","volume":"7","author":"Hamby","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1083\/jcb.201610102","article-title":"Regulation of RhoA by STAT3 coordinates glial scar formation","volume":"216","author":"Mukaino","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2006.10.057","article-title":"The effect of activated microglia on astrogliosis parameters in astrocyte cultures","volume":"1129","author":"Lucius","year":"2007","journal-title":"Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1002\/brx2.22","article-title":"SPEAC-seq: A new method to investigate astrocyte-microglia crosstalk","volume":"1","author":"Tang","year":"2023","journal-title":"Brain-X"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/416636a","article-title":"Chondroitinase ABC promotes functional recovery after spinal cord injury","volume":"416","author":"Bradbury","year":"2002","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.4103\/1673-5374.187023","article-title":"The complex contribution of the astrocyte scar","volume":"11","author":"Fitzgerald","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.4103\/1673-5374.187024","article-title":"The astrocyte scar\u2014Not so inhibitory after all?","volume":"11","author":"Tang","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.brainresbull.2010.06.015","article-title":"Manipulating the glial scar: Chondroitinase ABC as a therapy for spinal cord injury","volume":"84","author":"Bradbury","year":"2011","journal-title":"Brain Res. Bull."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"0460c1","DOI":"10.1088\/1741-2552\/ac028a","article-title":"Residual voltage as an ad-hoc indicator of electrode damage in biphasic electrical stimulation","volume":"18","author":"Krishnan","year":"2021","journal-title":"J. Neural Eng."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nri2294","article-title":"Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators","volume":"8","author":"Serhan","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sousa, A.B., and Barbosa, J.N. (2023). The Use of Specialized Pro-Resolving Mediators in Biomaterial-Based Immunomodulation. J. Funct. Biomater., 14.","DOI":"10.3390\/jfb14040223"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.biomaterials.2016.10.019","article-title":"Shifts in macrophage phenotype at the biomaterial interface via IL-4 eluting coatings are associated with improved implant integration","volume":"112","author":"Hachim","year":"2017","journal-title":"Biomaterials"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.4103\/1673-5374.313069","article-title":"CD4+ Tregs may be essential for solving astrocyte glial scar deadlock","volume":"16","author":"Kubick","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1172\/JCI43048","article-title":"Prevention of murine autoimmune diabetes by CCL22-mediated Treg recruitment to the pancreatic islets","volume":"121","author":"Montane","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1096\/fj.06-7227rev","article-title":"Resolution of inflammation: State of the art, definitions and terms","volume":"21","author":"Serhan","year":"2007","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nri.2015.4","article-title":"Specialized pro-resolving mediators: Endogenous regulators of infection and inflammation","volume":"16","author":"Basil","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Feron, K., Lim, R., Sherwood, C., Keynes, A., Brichta, A., and Dastoor, P.C. (2018). Organic Bioelectronics: Materials and Biocompatibility. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082382"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1586\/erd.09.58","article-title":"Development of bioactive conducting polymers for neural interfaces","volume":"7","author":"Lovell","year":"2010","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1002\/adma.201304496","article-title":"A Review of Organic and Inorganic Biomaterials for Neural Interfaces","volume":"26","author":"Fattahi","year":"2014","journal-title":"Adv. Mater."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23","DOI":"10.20517\/ss.2023.58","article-title":"Liquid metal neuro-electrical interface","volume":"4","author":"Zhang","year":"2024","journal-title":"Soft Sci."},{"key":"ref_61","first-page":"100118","article-title":"Engineering liquid metal-based implantable electrodes toward brain-machine interfaces","volume":"8","author":"Qian","year":"2023","journal-title":"Health Sci. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7337","DOI":"10.1021\/acsnano.4c18030","article-title":"Implantable Soft Neural Electrodes of Liquid Metals for Deep Brain Stimulation","volume":"19","author":"Kwon","year":"2025","journal-title":"ACS Nano"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"016014","DOI":"10.1088\/1741-2560\/12\/1\/016014","article-title":"PEDOT\u2013CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities","volume":"12","author":"Samba","year":"2015","journal-title":"J. Neural Eng."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6478","DOI":"10.1021\/acsabm.0c00861","article-title":"Carbon Nanotube Fibers for Neural Recording and Stimulation","volume":"3","author":"Alvarez","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"016008","DOI":"10.1088\/1741-2560\/12\/1\/016008","article-title":"Evaluation of poly(3,4-ethylenedioxythiophene)\/carbon nanotube neural electrode coatings for stimulation in the dorsal root ganglion","volume":"12","author":"Kolarcik","year":"2015","journal-title":"J. Neural Eng."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2424236","DOI":"10.1002\/adfm.202424236","article-title":"High-Performance MXene\/PEDOT-PSS Microscale Fiber Electrodes for Neural Recording and Stimulation","volume":"35","author":"Gou","year":"2025","journal-title":"Adv. Funct. Mater."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Gou, S., Yang, S., Cheng, Y., Yang, S., Liu, H., Li, P., and Du, Z. (2024). Applications of 2D Nanomaterials in Neural Interface. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168615"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Li, J., Cheng, Y., Gu, M., Yang, Z., Zhan, L., and Du, Z. (2023). Sensing and Stimulation Applications of Carbon Nanomaterials in Implantable Brain-Computer Interface. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065182"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Xia, Z., Arias-Gil, G., Deckert, M., Vollmer, M., Curran, A., Herrera-Molina, R., Brosch, M., Krug, K., Schmidt, B., and Ohl, F.W. (2019). Electrochemical Roughening and Carbon Nanotube Coating of Tetrodes for Chronic Single-Unit Recording. bioRxiv.","DOI":"10.1101\/738245"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7","DOI":"10.20517\/ss.2022.07","article-title":"PEDOT:PSS-based intrinsically soft and stretchable bioelectronics","volume":"2","author":"Li","year":"2022","journal-title":"Soft Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1601966","DOI":"10.1126\/sciadv.1601966","article-title":"Ultraflexible nanoelectronic probes form reliable, glial scar\u2013free neural integration","volume":"3","author":"Luan","year":"2017","journal-title":"Sci. Adv."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"101387","DOI":"10.1016\/j.isci.2020.101387","article-title":"Ultraflexible Neural Electrodes for Long-Lasting Intracortical Recording","volume":"23","author":"He","year":"2020","journal-title":"iScience"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1901775","DOI":"10.1002\/admi.201901775","article-title":"A Removable Insertion Shuttle for Ultraflexible Neural Probe Implantation with Stable Chronic Brain Electrophysiological Recording","volume":"7","author":"Zhang","year":"2020","journal-title":"Adv. Mater. Interfaces"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/nmat3468","article-title":"Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces","volume":"11","author":"Kozai","year":"2012","journal-title":"Nat. Mater."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.actbio.2017.02.010","article-title":"Ultrasoft microwire neural electrodes improve chronic tissue integration","volume":"53","author":"Du","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nnano.2015.115","article-title":"Syringe-injectable electronics","volume":"10","author":"Liu","year":"2015","journal-title":"Nat. Nanotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nmeth.3969","article-title":"Stable long-term chronic brain mapping at the single-neuron level","volume":"13","author":"Fu","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5894","DOI":"10.1073\/pnas.1705509114","article-title":"Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain","volume":"114","author":"Zhou","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"E10046","DOI":"10.1073\/pnas.1717695114","article-title":"Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology","volume":"114","author":"Fu","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1109\/TNSRE.2019.2932032","article-title":"A Method of Flexible Micro-Wire Electrode Insertion in Rodent for Chronic Neural Recording and a Device for Electrode Insertion","volume":"27","author":"Arafat","year":"2019","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"18","DOI":"10.20517\/ss.2023.08","article-title":"Injectable and tissue-conformable conductive hydrogel for MRI-compatible brain-interfacing electrodes","volume":"3","author":"Kim","year":"2023","journal-title":"Soft Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"39","DOI":"10.20517\/ss.2024.34","article-title":"Recent progress of hydrogels in brain-machine interface","volume":"4","author":"Zhang","year":"2024","journal-title":"Soft Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6283","DOI":"10.1021\/acsami.2c17025","article-title":"In Vivo Chronic Brain Cortex Signal Recording Based on a Soft Conductive Hydrogel Biointerface","volume":"15","author":"Rinoldi","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"17073","DOI":"10.1021\/acs.chemrev.2c00344","article-title":"Zwitterionic Biomaterials","volume":"122","author":"Li","year":"2022","journal-title":"Chem. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7894","DOI":"10.1021\/ac8015888","article-title":"Ultralow Fouling and Functionalizable Surface Chemistry Based on a Zwitterionic Polymer Enabling Sensitive and Specific Protein Detection in Undiluted Blood Plasma","volume":"80","author":"Yang","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Lee, H.C., Gaire, J., Currlin, S.W., McDermott, M.D., Park, K., and Otto, K.J. (2017). Foreign Body Response to Intracortical Microelectrodes Is Not Altered with Dip-Coating of Polyethylene Glycol (PEG). Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00513"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/sia.6376","article-title":"Functionalization of zwitterionic polymer brushes, do they remain antifouling?","volume":"50","author":"Hakobyan","year":"2018","journal-title":"Surf. Interface Anal."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0142-9612(00)00190-3","article-title":"Heparin coating of the stent graft\u2014Effects on platelets, coagulation and complement activation","volume":"22","author":"Christensen","year":"2001","journal-title":"Biomaterials"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/0161-5890(93)90329-A","article-title":"Complement activation during cardiopulmonary bypass: Effects of heparin-coating","volume":"30","author":"Pekna","year":"1993","journal-title":"Mol. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1900287","DOI":"10.1002\/adbi.201900287","article-title":"Zwitterionic Polymer Coating Suppresses Microglial Encapsulation to Neural Implants In Vitro and In Vivo","volume":"4","author":"Yang","year":"2020","journal-title":"Adv. Biosyst."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1016\/j.actbio.2012.03.001","article-title":"Polyethylene glycol-containing polyurethane hydrogel coatings for improving the biocompatibility of neural electrodes","volume":"8","author":"Rao","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1163\/092050610X488241","article-title":"Polylysine-Modified PEG-Based Hydrogels to Enhance the Neuro-Electrode Interface","volume":"22","author":"Rao","year":"2011","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3124","DOI":"10.1021\/acsabm.4c00156","article-title":"Photografted Zwitterionic Hydrogel Coating Durability for Reduced Foreign Body Response to Cochlear Implants","volume":"7","author":"Peel","year":"2024","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Gori, M., Giannitelli, S.M., Vadal\u00e0, G., Papalia, R., Zollo, L., Sanchez, M., Trombetta, M., Rainer, A., Di Pino, G., and Denaro, V. (2022). A Soft Zwitterionic Hydrogel as Potential Coating on a Polyimide Surface to Reduce Foreign Body Reaction to Intraneural Electrodes. Molecules, 27.","DOI":"10.3390\/molecules27103126"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41598-017-17877-y","article-title":"Peptide-based coatings for flexible implantable neural interfaces","volume":"8","author":"Righi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s11595-009-5753-6","article-title":"Cytocompatibility of self-assembled hydrogel from IKVAV-containing peptide amphiphile with neural stem cells","volume":"24","author":"Song","year":"2009","journal-title":"J. Wuhan Univ. Technol.-Mater. Sci. Ed."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/jbm.a.32228","article-title":"Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole\/BDNF-coated electrodes","volume":"91","author":"Evans","year":"2009","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1900072","DOI":"10.1002\/adbi.201900072","article-title":"Wafer-Scale Fabrication of Conducting Polymer Hydrogels for Microelectrodes and Flexible Bioelectronics","volume":"3","author":"Kleber","year":"2019","journal-title":"Adv. Biosyst."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"108985","DOI":"10.1016\/j.bioelechem.2025.108985","article-title":"Hybrid conducting polymer films promote neural outgrowth and neural-electrode integration In Vitro","volume":"165","author":"Shakibania","year":"2025","journal-title":"Bioelectrochemistry"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"618","DOI":"10.3390\/bios5040618","article-title":"In Vivo Electrochemical Analysis of a PEDOT\/MWCNT Neural Electrode Coating","volume":"5","author":"Alba","year":"2015","journal-title":"Biosensors"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1109\/TBME.2015.2445713","article-title":"Chronic In Vivo Evaluation of PEDOT\/CNT for Stable Neural Recordings","volume":"63","author":"Kozai","year":"2016","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6515","DOI":"10.1039\/C5TC00145E","article-title":"Poly(3,4-ethylenedioxythiophene)-ionic liquid coating improves neural recording and stimulation functionality of MEAs","volume":"3","author":"Du","year":"2015","journal-title":"J. Mater. Chem. C"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2104701","DOI":"10.1002\/advs.202104701","article-title":"Poly(3,4-ethylenedioxythiophene)-Based Neural Interfaces for Recording and Stimulation: Fundamental Aspects and In Vivo Applications","volume":"9","author":"Bianchi","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"42148","DOI":"10.1021\/acsami.5c02872","article-title":"Flexible Depth Probes with PEDOT:PSS Microelectrodes for Chronic Recording and Stimulation","volume":"17","author":"Ivanov","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Wille, I., Harre, J., Oehmichen, S., Lindemann, M., Menzel, H., Ehlert, N., Lenarz, T., Warnecke, A., and Behrens, P. (2022). Development of Neuronal Guidance Fibers for Stimulating Electrodes: Basic Construction and Delivery of a Growth Factor. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.776890"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.brainres.2007.02.024","article-title":"Dexamethasone-coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes","volume":"1148","author":"Zhong","year":"2007","journal-title":"Brain Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1703988","DOI":"10.1002\/adfm.201703988","article-title":"Electrically Controlled Neurochemical Release from Dual-Layer Conducting Polymer Films for Precise Modulation of Neural Network Activity in Rat Barrel Cortex","volume":"28","author":"Du","year":"2018","journal-title":"Adv. Funct. Mater."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.biomaterials.2017.03.019","article-title":"Actively controlled release of dexamethasone from neural microelectrodes in a chronic in vivo study","volume":"129","author":"Boehler","year":"2017","journal-title":"Biomaterials"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"016004","DOI":"10.1088\/1741-2560\/10\/1\/016004","article-title":"Conducting polymer coated neural recording electrodes","volume":"10","author":"Harris","year":"2013","journal-title":"J. Neural Eng."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/pi.3168","article-title":"New carbon nanotube\u2013conducting polymer composite electrodes for drug delivery applications","volume":"61","author":"Xiao","year":"2012","journal-title":"Polym. Int."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3","DOI":"10.20517\/ss.2022.25","article-title":"Electro-assisted assembly of conductive polymer and soft hydrogel into core-shell hybrids","volume":"3","author":"Paterson","year":"2023","journal-title":"Soft Sci."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Krishnan, A., and Kelly, S.K. (September, January 28). On the cause and control of residual voltage generated by electrical stimulation of neural tissue. Proceedings of the 2012 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, San Diego, CA, USA.","DOI":"10.1109\/EMBC.2012.6346819"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2400114","DOI":"10.1002\/anbr.202400114","article-title":"Long-Term Neural Recording Performance of PEDOT\/CNT\/Dexamethasone-Coated Electrode Array Implanted in Visual Cortex of Rats","volume":"5","author":"Golabchi","year":"2025","journal-title":"Adv. NanoBiomed Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1016\/j.biomaterials.2005.12.021","article-title":"Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery","volume":"27","author":"Kim","year":"2006","journal-title":"Biomaterials"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/adma.200501726","article-title":"Conducting-Polymer Nanotubes for Controlled Drug Release","volume":"18","author":"Abidian","year":"2006","journal-title":"Adv. Mater."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"104648","DOI":"10.1016\/j.jddst.2023.104648","article-title":"PLGA implants for controlled dexamethasone delivery: Impact of the polymer chemistry","volume":"86","author":"Wachowiak","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1007\/s13346-018-0516-6","article-title":"Release pattern of dexamethasone after administration through an implant-mediated drug delivery device with an active plunger of super absorbent polymer","volume":"8","author":"Yang","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1021\/acs.biochem.8b00122","article-title":"Tissue-like Neural Probes for Understanding and Modulating the Brain","volume":"57","author":"Hong","year":"2018","journal-title":"Biochemistry"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1021\/acs.accounts.7b00547","article-title":"Mesh Nanoelectronics: Seamless Integration of Electronics with Tissues","volume":"51","author":"Dai","year":"2018","journal-title":"Acc. Chem. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"036022","DOI":"10.1088\/1741-2552\/aa6632","article-title":"The design of and chronic tissue response to a composite nerve electrode with patterned stiffness","volume":"14","author":"Freeberg","year":"2017","journal-title":"J. Neural Eng."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"123929","DOI":"10.1016\/j.biomaterials.2025.123929","article-title":"A comparative study assessing neural recording quality and inflammatory tissue response between stiff and flexible microelectrode arrays","volume":"329","author":"Dhawan","year":"2026","journal-title":"Biomaterials"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jconrel.2005.10.027","article-title":"Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode","volume":"110","author":"Wadhwa","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Lazic, S.E. (2010). The problem of pseudoreplication in neuroscientific studies: Is it affecting your analysis?. BMC Neurosci., 11.","DOI":"10.1186\/1471-2202-11-5"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nn.3648","article-title":"A solution to dependency: Using multilevel analysis to accommodate nested data","volume":"17","author":"Aarts","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"022002","DOI":"10.1088\/1748-605X\/ad1f78","article-title":"Neural repair and regeneration interfaces: A comprehensive review","volume":"19","author":"Sha","year":"2024","journal-title":"Biomed. Mater."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1039\/D5CS01422K","article-title":"Tissue-bioelectronics interfaces","volume":"55","author":"Li","year":"2026","journal-title":"Chem. Soc. Rev."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"21","DOI":"10.20517\/ss.2024.01","article-title":"Electrolyte engineering in organic electrochemical transistors for advanced electrophysiology","volume":"4","author":"Zhu","year":"2024","journal-title":"Soft Sci."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"9092","DOI":"10.1021\/acs.chemrev.4c00862","article-title":"Neural vs Neuromorphic Interfaces: Where Are We Standing?","volume":"125","author":"Rana","year":"2025","journal-title":"Chem. Rev."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Cunha, R.S., Rossi, E.A., Santana, T.A.D., Costa-Ferro, Z.S.M., and Souza, B.S.D.F. (2025). Chondroitinase ABC in spinal cord injury: Advances in delivery strategies and therapeutic synergies. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1604502"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6752\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:19:33Z","timestamp":1785385173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":129,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156752"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156752","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}