title: Protease-degradable PEG-maleimide coating with on-demand release of IL-1Ra to improve tissue response to neural electrodes.
abstract: Neural electrodes are an important part of brain-machine interface devices that can restore functionality to patients with sensory and movement disorders. Chronically implanted neural electrodes induce an unfavorable tissue response which includes inflammation, scar formation, and neuronal cell death, eventually causing loss of electrode function. We developed a poly(ethylene glycol) hydrogel coating for neural electrodes with non-fouling characteristics, incorporated an anti-inflammatory agent, and engineered a stimulus-responsive degradable portion for on-demand release of the anti-inflammatory agent in response to inflammatory stimuli. This coating reduces in vitro glial cell adhesion, cell spreading, and cytokine release compared to uncoated controls. We also analyzed the in vivo tissue response using immunohistochemistry and microarray qRT-PCR. Although no differences were observed among coated and uncoated electrodes for inflammatory cell markers, lower IgG penetration into the tissue around PEG+IL-1Ra coated electrodes indicates an improvement in blood-brain barrier integrity. Gene expression analysis showed higher expression of IL-6 and MMP-2 around PEG+IL-1Ra samples, as well as an increase in CNTF expression, an important marker for neuronal survival. Importantly, increased neuronal survival around coated electrodes compared to uncoated controls was observed. Collectively, these results indicate promising findings for an engineered coating to increase neuronal survival and improve tissue response around implanted neural electrodes.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Stacie M
authors.initials: SM
authors.lastname: Gutowski
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Shoemaker
authors.affiliation: Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA; Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Kellie L
authors.initials: KL
authors.lastname: Templeman
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Latour
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Bellamkonda
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA; Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: LaPlaca
authors.affiliation: Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA; Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: andres.garcia@me.gatech.edu.
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D004567:Electrodes, Implanted; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007074:Immunoglobulin G / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
chemical_list: D020099:Coated Materials, Biocompatible; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D008301:Maleimides; C043592:maleimide; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D002809:Chondroitin Sulfates; D010447:Peptide Hydrolases
keywords: Astrocyte; Electrode; Hydrogel; Inflammation; Neural cell; Peptide