title: Surface immobilization of neural adhesion molecule L1 for improving the biocompatibility of chronic neural probes: In vitro characterization.
abstract: Silicon-based implantable neural electrode arrays are known to experience failure during long-term recording, partially due to host tissue responses. Surface modification and immobilization of biomolecules may provide a means to improve their biocompatibility and integration within the host brain tissue. Previously, the laminin biomolecule or laminin fragments have been used to modify the neural probe's silicon surface to promote neuronal attachment and growth. Here we report the successful immobilization of the L1 biomolecule on a silicon surface. L1 is a neuronal adhesion molecule that can specifically promote neurite outgrowth and neuronal survival. Silane chemistry and the heterobifunctional coupling agent 4-maleimidobutyric acid N-hydroxysuccinimide ester (GMBS) were used to covalently bind these two biomolecules onto the surface of silicon dioxide wafers, which mimic the surface of silicon-based implantable neural probes. After covalent binding of the biomolecules, polyethylene glycol (PEG)-NH(2) was used to cap the unreacted GMBS groups. Surface immobilization was verified by goniometry, dual polarization interferometry, and immunostaining techniques. Primary murine neurons or astrocytes were used to evaluate the modified silicon surfaces. Both L1- and laminin-modified surfaces promoted neuronal attachment, while the L1-modified surface demonstrated significantly enhanced levels of neurite outgrowth (p<0.05). In addition, the laminin-modified surface promoted astrocyte attachment, while the L1-modified surface showed significantly reduced levels of astrocyte attachment relative to the laminin-modified surface and other controls (p<0.05). These results demonstrate the ability of the L1-immobilized surface to specifically promote neuronal growth and neurite extension, while inhibiting the attachment of astrocytes, one of the main cellular components of the glial sheath. Such unique properties present vast potentials to improve the biocompatibility and chronic recording performance of neural probes.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, 3501 Fifth Avenue, 5063 Biomedical Science Tower 3, Pittsburgh, PA 15261, USA.
authors.forename: Erdrin
authors.initials: E
authors.lastname: Azemi
authors.forename: William R
authors.initials: WR
authors.lastname: Stauffer
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gostock
authors.forename: Carl F
authors.initials: CF
authors.lastname: Lagenaur
authors.forename: Xinyan Tracy
authors.initials: XT
authors.lastname: Cui
mesh_terms: D000327:Adsorption; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000494:pharmacology*; D008422:Materials Testing; D008839:Microelectrodes; D039842:Neural Cell Adhesion Molecule L1 / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011092:Polyethylene Glycols / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry; D013499:Surface Properties
chemical_list: D020099:Coated Materials, Biocompatible; D039842:Neural Cell Adhesion Molecule L1; D011092:Polyethylene Glycols; D012822:Silicon Dioxide