title: Multifunctional hydrogel coatings on the surface of neural cuff electrode for improving electrode-nerve tissue interfaces.
abstract: Recently, implantable neural electrodes have been developed for recording and stimulation of the nervous system. However, when the electrode is implanted onto the nerve trunk, the rigid polyimide has a risk of damaging the nerve and can also cause inflammation due to a mechanical mismatch between the stiff polyimide and the soft biological tissue. These processes can interrupt the transmission of nerve signaling. In this paper, we have developed a nerve electrode coated with PEG hydrogel that contains poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with anti-inflammatory cyclosporin A (CsA). Micro-wells were introduced onto the electrode in order to increase their surface area. This allows for loading a high-dose of the drug. Additionally, chemically treating the surface with aminopropylmethacrylamide can improve the adhesive interface between the electrode and the hydrogel. The surface of the micro-well cuff electrode (MCE) coated with polyethylene glycol (PEG) hydrogel and drug loaded PLGA microspheres (MS) were characterized by SEM and optical microscopy. Additionally, the conductive polymers, poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT/PSS), were formed on the hydrogel layer for improving the nerve signal quality, and then characterized for their electrochemical properties. The loading efficiencies and release profiles were investigated by High Performance Liquid Chromatography (HPLC). The drug loaded electrode resulted in a sustained release of CsA. Moreover, the surface coated electrode with PEG hydrogel and CsA loaded MP showed a significantly decreased fibrous tissue deposition and increased axonal density in animal tests. We expect that the developed nerve electrode will minimize the tissue damage during regeneration of the nervous system.
  
  
  
  The nerve electrodes are used for interfacing with the central nervous system (CNS) or with the peripheral nervous system (PNS). The interface electrodes should facilitate a closed interconnection with the nerve tissue and provide for selective stimulation and recording from multiple, independent, neurons of the neural system. In this case, an extraneural electrodes such as cuff and perineural electrodes are widely investigated because they can completely cover the nerve trunk and provide for a wide interface area. In this study, we have designed and prepared a functionalized nerve cuff electrode coated with PEG hydrogel containing Poly lactic-co-glycol acid (PLGA) microspheres (MS) loaded with cyclosporine A (CsA). To our knowledge, our findings suggest that surface coating a soft-hydrogel along with an anti-inflammatory drug loaded MS can be a useful strategy for improving the long-term biocompatibility of electrodes.
authors.affiliation: Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Mechanical and Aerospace Engineering, The George Washington University, DC 20052, USA.
authors.forename: Dong Nyoung
authors.initials: DN
authors.lastname: Heo
authors.affiliation: Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Song
authors.affiliation: Department of Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
authors.forename: Han-Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Center for BioMicroSystems, Korea Institute of Science and Technology, Seoul 02455, Republic of Korea.
authors.forename: Yi Jae
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Wan-Kyu
authors.initials: WK
authors.lastname: Ko
authors.affiliation: Department of Dentistry, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Dentistry, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Lee
authors.affiliation: Center for BioMicroSystems, Korea Institute of Science and Technology, Seoul 02455, Republic of Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Mechanical and Aerospace Engineering, The George Washington University, DC 20052, USA.
authors.forename: Lijie Grace
authors.initials: LG
authors.lastname: Zhang
authors.affiliation: Center for BioMicroSystems, Korea Institute of Science and Technology, Seoul 02455, Republic of Korea.
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Kang
authors.affiliation: Department of Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Do
authors.affiliation: Center for BioMicroSystems, Korea Institute of Science and Technology, Seoul 02455, Republic of Korea. Electronic address: shleekist@kist.re.kr.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: kwoni@khu.ac.kr.
authors.forename: Il Keun
authors.initials: IK
authors.lastname: Kwon
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D016572:Cyclosporine / Q000737:chemistry*; D004558:Electric Stimulation / Q000379:methods; D004566:Electrodes; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D023181:Antimicrobial Cationic Peptides; D020100:Hydrogels; C045866:peptide-Gly-Leu-amide; D011092:Polyethylene Glycols; D016572:Cyclosporine; C000595209:polyethylene glycol 1000
keywords: Cuff electrode; Cyclosporine A; Drug delivery; Hydrogel coating; Neural signal recording; Sciatic nerve