Multifunctional Nanobiomaterials for Neural Interfaces

Neural electrodes are designed to interface with the nervous system and provide control signals for neural prostheses. However, robust and reliable chronic recording and stimulation remains a challenge for neural electrodes. Here, a novel method for the fabrication of soft, low impedance, high charge density, and controlled releasing nanobiomaterials that can be used for the surface modification of neural microelectrodes to stabilize the electrode/ tissue interface is reported. The fabrication process includes electrospinning of anti-inflammatory drug-incorporated biodegradable nanofibers, encapsulation of these nanofibers by an alginate hydrogel layer, followed by electrochemical polymerization of conducting polymers around the electrospun drug-loaded nanofibers to form nanotubes and within the alginate hydrogel scaffold to form cloud-like nanostructures. The threedimensional conducting polymer nanostructures significantly decrease the electrode impedance and increase the charge capacity density. Dexamethasone release profiles show that the alginate hydrogel coating slows down the release of the drug, significantly reducing the burst effect. These multifunctional materials are expected to be of interest for a variety of electrode/tissue interfaces in biomedical devices.

[1]  Teruo Okano,et al.  Pulsatile drug release control using hydrogels. , 2002, Advanced drug delivery reviews.

[2]  Michel Vert,et al.  STRUCTURE – PROPERTY RELATIONSHIP IN THE CASE OF THE DEGRADATION OF MASSIVE ALIPHATIC POLY – (-HYDROXY ACIDS) IN AQUEOUS MEDIA, PART 1: DEGRADATION OF LACTIDE - GLYCOLIDE COPOLYMERS: PLA 37.5 GA 25 AND PLA 75 GA 25 , 1990 .

[3]  Geoffrey M. Spinks,et al.  Conducting polymers - bridging the bionic interface. , 2007, Soft matter.

[4]  Teruo Okano,et al.  Hydrogels: Swelling, Drug Loading, and Release , 1992, Pharmaceutical Research.

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

[6]  D. Szarowski,et al.  Cerebral Astrocyte Response to Micromachined Silicon Implants , 1999, Experimental Neurology.

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

[8]  J. Desbrières,et al.  Physico-chemical characterization of Ca-alginate microparticles produced with different methods. , 1999, Biomaterials.

[9]  D. Robinson,et al.  The electrical properties of metal microelectrodes , 1968 .

[10]  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.

[11]  R. Cameron,et al.  The effect of initial polymer morphology on the degradation and drug release from polyglycolide. , 2002, Biomaterials.

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

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

[14]  A. Göpferich,et al.  Why degradable polymers undergo surface erosion or bulk erosion. , 2002, Biomaterials.

[15]  Wayne R. Gombotz,et al.  Protein release from alginate matrices. , 1998, Advanced drug delivery reviews.

[16]  David C. Martin,et al.  Experimental and theoretical characterization of implantable neural microelectrodes modified with conducting polymer nanotubes. , 2008, Biomaterials.

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

[18]  E. Maynard,et al.  A technique to prevent dural adhesions to chronically implanted microelectrode arrays , 2000, Journal of Neuroscience Methods.

[19]  D. Wise,et al.  Medical Applications of Controlled Release , 2019 .

[20]  Michel Vert,et al.  Structure-property relationships in the case of the degradation of massive poly(α-hydroxy acids) in aqueous media , 1990 .

[21]  Michel Vert,et al.  Structure-property relationships in the case of the degradation of massive aliphatic poly-(α-hydroxy acids) in aqueous media , 1990 .

[22]  J N Turner,et al.  Selective adhesion of astrocytes to surfaces modified with immobilized peptides. , 2002, Biomaterials.

[23]  Andreas Greiner,et al.  Nanostructured Fibers via Electrospinning , 2001 .

[24]  B. Lipworth Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. , 1999, Archives of internal medicine.

[25]  S. Li,et al.  Further investigations on the hydrolytic degradation of poly (DL-lactide). , 1999, Biomaterials.

[26]  G. Wallace,et al.  Preparation of hydrogel/conducting polymer composites , 1994 .

[27]  J. Heinze,et al.  Electrochemical and spectroscopic characterization of polyalkylenedioxythiophenes , 1994 .

[28]  Christine E. Schmidt,et al.  Conducting polymers in biomedical engineering , 2007 .

[29]  R. J. Vetter,et al.  Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex , 2003, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[30]  R. Normann,et al.  Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex , 1998, Journal of Neuroscience Methods.

[31]  T. Park,et al.  Poly(L-lactic acid)/pluronic blends : characterization of phase separation behavior, degradation, and morphology and use as protein-releasing matrices , 1992 .

[32]  R Langer,et al.  New methods of drug delivery. , 1990, Science.

[33]  Thomas M. McKenna,et al.  Enabling Technologies for Cultured Neural Networks , 1994 .

[34]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[35]  Benjamin Chu,et al.  Structure and morphology changes during in vitro degradation of electrospun poly(glycolide-co-lactide) nanofiber membrane. , 2003, Biomacromolecules.

[36]  J. Reynolds,et al.  Poly(3,4‐ethylenedioxythiophene) and Its Derivatives: Past, Present, and Future , 2000 .

[37]  M. Alexander,et al.  Principles of Neural Science , 1981 .

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

[39]  K. Wise,et al.  Performance of planar multisite microprobes in recording extracellular single-unit intracortical activity , 1988, IEEE Transactions on Biomedical Engineering.

[40]  Jayanth Panyam,et al.  Biodegradable nanoparticles for drug and gene delivery to cells and tissue. , 2003, Advanced drug delivery reviews.

[41]  R. Arshady Preparation of biodegradable microspheres and microcapsules: 2. Polyactides and related polyesters , 1991 .

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

[43]  K. Shakesheff,et al.  Polymeric systems for controlled drug release. , 1999, Chemical reviews.

[44]  M. Berggren,et al.  Electronic control of Ca2+ signalling in neuronal cells using an organic electronic ion pump. , 2007, Nature materials.

[45]  D. Mooney,et al.  Polymeric system for dual growth factor delivery , 2001, Nature Biotechnology.

[46]  M. Abidian,et al.  Conducting‐Polymer Nanotubes for Controlled Drug Release , 2006, Advanced materials.

[47]  R. Langer,et al.  Biodegradable polymers as drug delivery systems , 1990 .

[48]  F. Jonas,et al.  Poly(alkylenedioxythiophene)s—new, very stable conducting polymers , 1992 .

[49]  A. M. Reed,et al.  Biodegradable polymers for use in surgery — poly(glycolic)/poly(Iactic acid) homo and copolymers: 2. In vitro degradation , 1981 .

[50]  D. Kipke,et al.  Long-term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex. , 1999, Brain research. Brain research protocols.

[51]  C. Tanford Macromolecules , 1994, Nature.

[52]  Jiping He,et al.  Glial cell and fibroblast cytotoxicity study on plasma-deposited diamond-like carbon coatings. , 2003, Biomaterials.

[53]  Cato T Laurencin,et al.  Electrospun nanofibrous structure: a novel scaffold for tissue engineering. , 2002, Journal of biomedical materials research.

[54]  D. Long,et al.  The Clinical Effects of a Synthetic Gluco-Corticoid used for Brain Edema in the Practice of Neurosurgery , 1972 .

[55]  Josef Hormes,et al.  The thermal ageing of poly(3,4-ethylenedioxythiophene). An investigation by X-ray absorption and X-ray photoelectron spectroscopy , 1995 .

[56]  J. Reynolds,et al.  Electrochemistry of Poly(3,4‐alkylenedioxythiophene) Derivatives , 2003 .

[57]  F. Jonas,et al.  Conductive modifications of polymers with polypyrroles and polythiophenes , 1991 .

[58]  A. Göpferich,et al.  Mechanisms of polymer degradation and erosion. , 1996, Biomaterials.

[59]  Daryl R. Kipke,et al.  Wireless implantable microsystems: high-density electronic interfaces to the nervous system , 2004, Proceedings of the IEEE.

[60]  R Langer,et al.  Erosion kinetics of hydrolytically degradable polymers. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[61]  Warren M. Grill,et al.  Selection of stimulus parameters for deep brain stimulation , 2004, Clinical Neurophysiology.

[62]  D.B. McCreery,et al.  Charge density and charge per phase as cofactors in neural injury induced by electrical stimulation , 1990, IEEE Transactions on Biomedical Engineering.

[63]  M. Shive,et al.  Biodegradation and biocompatibility of PLA and PLGA microspheres , 1997 .

[64]  D. Edell,et al.  Factors influencing the biocompatibility of insertable silicon microshafts in cerebral cortex , 1992, IEEE Transactions on Biomedical Engineering.

[65]  Kwangsok Kim,et al.  Control of degradation rate and hydrophilicity in electrospun non-woven poly(D,L-lactide) nanofiber scaffolds for biomedical applications. , 2003, Biomaterials.

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

[67]  A. Pennings,et al.  Crystal structure, conformation and morphology of solution-spun poly(L-lactide) fibers , 1990 .

[68]  Daryl R. Kipke,et al.  Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes , 2006, IEEE Transactions on Biomedical Engineering.

[69]  David C. Martin,et al.  Electrochemical fabrication of conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) nanofibrils on microfabricated neural prosthetic devices , 2007, Journal of biomaterials science. Polymer edition.

[70]  J. Melby Drug spotlight program: systemic corticosteroid therapy: pharmacology and endocrinologic considerations. , 1974, Annals of internal medicine.

[71]  R. A. Jain,et al.  The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. , 2000, Biomaterials.

[72]  S.F. Cogan,et al.  Sputtered iridium oxide films (SIROFs) for low-impedance neural stimulation and recording electrodes , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[73]  R. Misra,et al.  Biomaterials , 2008 .

[74]  Jerald D. Kralik,et al.  Chronic, multisite, multielectrode recordings in macaque monkeys , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[75]  David C. Martin,et al.  Fuzzy gold electrodes for lowering impedance and improving adhesion with electrodeposited conducting polymer films , 2003 .

[76]  David C. Martin,et al.  Microporous conducting polymers on neural microelectrode arrays: I Electrochemical deposition , 2004 .

[77]  E. Smela Conjugated Polymer Actuators for Biomedical Applications , 2003 .

[78]  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.

[79]  J. Csicsvari,et al.  Massively parallel recording of unit and local field potentials with silicon-based electrodes. , 2003, Journal of neurophysiology.

[80]  M Dunne,et al.  Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles. , 2000, Biomaterials.

[81]  王晓燕 Arch Intern Med:住院增加老年人出院后骨折危险 , 2009 .