Biofunctionalized peptide-based hydrogels provide permissive scaffolds to attract neurite outgrowth from spiral ganglion neurons

Colloids Surf B Biointerfaces. 2017 Jan 1;149:105-114. doi: 10.1016/j.colsurfb.2016.10.003. Epub 2016 Oct 4.

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.

Keywords: Biofunctionalized peptide-based hydrogel; Cochlear implant; Neurite outgrowth; Spiral ganglion neuron.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cochlea / drug effects
  • Cochlea / physiology
  • Cochlea / ultrastructure
  • Cochlear Implants
  • Female
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Laminin / metabolism
  • Laminin / pharmacology
  • Male
  • Mice
  • Neurites / drug effects*
  • Neurites / physiology
  • Neurites / ultrastructure
  • Neuronal Outgrowth / drug effects*
  • Neuronal Outgrowth / physiology
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Spiral Ganglion / drug effects*
  • Spiral Ganglion / growth & development
  • Spiral Ganglion / physiology
  • Spiral Ganglion / ultrastructure
  • Tissue Culture Techniques
  • Tissue Scaffolds*

Substances

  • Brain-Derived Neurotrophic Factor
  • Hydrogels
  • Laminin
  • Peptides
  • RADA16-I