title: Biohybrid cochlear implants in human neurosensory restoration.
abstract: The success of cochlear implantation may be further improved by minimizing implantation trauma. The physical trauma of implantation and subsequent immunological sequelae can affect residual hearing and the viability of the spiral ganglion. An ideal electrode should therefore decrease post-implantation trauma and provide support to the residual spiral ganglion population. Combining a flexible electrode with cells producing and releasing protective factors could present a potential means to achieve this. Mononuclear cells obtained from bone marrow (BM-MNC) consist of mesenchymal and hematopoietic progenitor cells. They possess the innate capacity to induce repair of traumatized tissue and to modulate immunological reactions.
  
  
  
  Human bone marrow was obtained from the patients that received treatment with biohybrid electrodes. Autologous mononuclear cells were isolated from bone marrow (BM-MNC) by centrifugation using the Regenlab™ THT-centrifugation tubes. Isolated BM-MNC were characterised using flow cytometry. In addition, the release of cytokines was analysed and their biological effect tested on spiral ganglion neurons isolated from neonatal rats. Fibrin adhesive (Tisseal™) was used for the coating of silicone-based cochlear implant electrode arrays for human use in order to generate biohybrid electrodes. Toxicity of the fibrin adhesive and influence on insertion, as well on the cell coating, was investigated. Furthermore, biohybrid electrodes were implanted in three patients.
  
  
  
  Human BM-MNC release cytokines, chemokines, and growth factors that exert anti-inflammatory and neuroprotective effects. Using fibrin adhesive as a carrier for BM-MNC, a simple and effective cell coating procedure for cochlear implant electrodes was developed that can be utilised on-site in the operating room for the generation of biohybrid electrodes for intracochlear cell-based drug delivery. A safety study demonstrated the feasibility of autologous progenitor cell transplantation in humans as an adjuvant to cochlear implantation for neurosensory restoration.
  
  
  
  This is the first report of the use of autologous cell transplantation to the human inner ear. Due to the simplicity of this procedure, we hope to initiate its widespread utilization in various fields.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Cluster of Excellence "Hearing4all", Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Roemer
authors.affiliation: Institute for Cellular Therapeutics, IFB-Tx, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Köhl
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Cluster of Excellence "Hearing4all", Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Omid
authors.initials: O
authors.lastname: Majdani
authors.affiliation: Institute for Cellular Therapeutics, IFB-Tx, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klöß
authors.affiliation: Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Falk
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Cluster of Excellence "Hearing4all", Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Haumann
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Cluster of Excellence "Hearing4all", Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lenarz
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.|Cluster of Excellence "Hearing4all", Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Kral
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. warnecke.Athanasia@mh-hannover.de.|Cluster of Excellence "Hearing4all", Carl-Neuberg-Str. 1, 30625, Hannover, Germany. warnecke.Athanasia@mh-hannover.de.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Warnecke
mesh_terms: D000328:Adult; D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology*; D019929:Cochlear Implantation / Q000379:methods; D003054:Cochlear Implants; D004567:Electrodes, Implanted; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D009490:Neurosecretory Systems / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000166:cytology; D014182:Transplantation, Autologous / Q000379:methods; D014947:Wounds and Injuries / Q000628:therapy*; D055815:Young Adult
keywords: Biohybrid electrode; Bone marrow-derived mononuclear cells; Cochlear implants; Hearing loss