Biohybrid cochlear implants in human neurosensory restoration

Abstract

BackgroundThe 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.MethodsHuman 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.ResultsHuman 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.ConclusionThis 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.

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

“…(iii) Coating the electrode carrier with cells producing therapeutic molecules. The advantage of this approach is to be a source of complex macromolecules (56)(57)(58)(59)(60). However, stem cells are limited to the production of bioactive substances that are naturally produced in the body.…”

Cochlear Implant – State of the Art

“…Stem cell transplantation can be performed by so-called bio-hybrid electrodes. After gaining the stem cells from the bone marrow of the sternum, they are applied together with the bio-hybrid electrodes onto the electrode surface by means of polymer and the electrode is then inserted carefully into the scala tympani ( Figure 44) [68]. The secretion of growth factors is also important for preservation of residual hearing.…”

Delivering Therapeutics to the Cochlea: The Importance of the Patient’s Perspective

“…Finally, cochlear implants are being designed to deliver drugs to the cochlea. Approaches include coating the electrode in biodegradable eluting polymers or cells to release factors that reduce trauma and promote spiral ganglion survival (Roemer et al, 2016;Scheper et al, 2019). These technologies aim to enhance the benefit gained from cochlear implants, so are likely to be acceptable to patients already undergoing cochlear implant surgery.…”