title: Biofunctionalized peptide-based hydrogels provide permissive scaffolds to attract neurite outgrowth from spiral ganglion neurons.
abstract: Cochlear implants (CI) allow for hearing rehabilitation in patients with sensorineural hearing loss or deafness. Restricted CI performance results from the spatial gap between spiral ganglion neurons and the CI, causing current spread that limits spatially restricted stimulation and impairs frequency resolution. This may be substantially improved by guiding peripheral processes of spiral ganglion neurons towards and onto the CI electrode contacts. An injectable, peptide-based hydrogel was developed which may provide a permissive scaffold to facilitate neurite growth towards the CI. To test hydrogel capacity to attract spiral ganglion neurites, neurite outgrowth was quantified in an in vitro model using a custom-designed hydrogel scaffold and PuraMatrix®. Neurite attachment to native hydrogels is poor, but significantly improved by incorporation of brain-derived neurotrophic factor (BDNF), covalent coupling of the bioactive laminin epitope IKVAV and the incorporation a full length laminin to hydrogel scaffolds. Incorporation of full length laminin protein into a novel custom-designed biofunctionalized hydrogel (IKVAV-GGG-SIINFEKL) allows for neurite outgrowth into the hydrogel scaffold. The study demonstrates that peptide-based hydrogels can be specifically biofunctionalized to provide a permissive scaffold to attract neurite outgrowth from spiral ganglion neurons. Such biomaterials appear suitable to bridge the spatial gap between neurons and the CI.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany. Electronic address: cfrick@gmx.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Frick
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany. Electronic address: marcus.mueller@uni-tuebingen.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.affiliation: EMC microcollections GmbH, DE-72070 Tübingen, Germany. Electronic address: wank@microcollections.de.
authors.forename: Ute
authors.initials: U
authors.lastname: Wank
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany. Electronic address: anke.tropitzsch@med.uni-tuebingen.de.
authors.forename: Anke
authors.initials: A
authors.lastname: Tropitzsch
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany. Electronic address: benedikt.kramer@umm.de.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Kramer
authors.affiliation: Department of Clinical Neurosciences, Service of Otorhinolaryngology, Head & Neck Surgery, HUG, University Hospital of Geneva, CH-1211 Genève 14, Switzerland. Electronic address: Pascal.Senn@hcuge.ch.
authors.forename: Pascal
authors.initials: P
authors.lastname: Senn
authors.affiliation: Department of Surgical Sciences, Head and Neck Surgery, Section of Otolaryngology, Uppsala University Hospital, Departments of Otolaryngology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Electronic address: Helge.Rask-Andersen@akademiska.se.
authors.forename: Helge
authors.initials: H
authors.lastname: Rask-Andersen
authors.affiliation: EMC microcollections GmbH, DE-72070 Tübingen, Germany. Electronic address: wiesmueller@microcollections.de.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wiesmüller
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre, Eberhard Karls University Tübingen, DE-72076 Tübingen, Germany. Electronic address: hubert.loewenheim@uni-tuebingen.de.
authors.forename: Hubert
authors.initials: H
authors.lastname: Löwenheim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D003054:Cochlear Implants; D005260:Female; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D016501:Neurites / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D000071446:Neuronal Outgrowth / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013136:Spiral Ganglion / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology / Q000648:ultrastructure; D046509:Tissue Culture Techniques; D054457:Tissue Scaffolds
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020100:Hydrogels; D007797:Laminin; D010455:Peptides; C546681:RADA16-I
keywords: Biofunctionalized peptide-based hydrogel; Cochlear implant; Neurite outgrowth; Spiral ganglion neuron