According to the World Health Organization, about 5 % of the world’s population, i.e., more than 300 million people, suffer from disabling hearing loss. For rehabilitation of severe to profound hearing loss, patients are treated with cochlear implantation. Currently, four manufacturers (MedEl, Advanced Bionics Cooperation, Cochlear Cooperation and MXM/Neurolec/Oticon) are FDA approved and provide different electrode designs [1, 2]. In addition, novel companies providing cochlear implants, e.g., the Venus cochlear implant system provided by Nurotron Biotechnology, are emerging. All available implants share common key features: an external device for conversion of acoustic energy into an electrical signal [14]. This signal is transmitted subcutaneously to an implanted internal signal receiver that is used to drive the stimulation of the spiral ganglion neurons [3]. An electrode carrier consisting of platinum contacts embedded in silicone is connected to this implanted device and is inserted into the scala tympani of the cochlea [3]. Differences between the devices include the length, the stiffness, and the design of the electrode. For electrical stimulation of the auditory system, a full circuit loop from an active electrode to a second return electrode is necessary [1]. The mode of activation is either monopolar or bipolar [3]. An inactive reference electrode located outside the cochlea is needed for monopolar stimulation, whereas bipolar stimulation is performed by using two neighbouring intracochlear electrodes [3]. A recent survey has evaluated the complications after cochlear implantation showing that the overall incidence is about 20 % [5]. Infection of the skin flap covering the implant, seroma or hematoma, foreign body reaction, tinnitus, disequilibrium, device failure, neurological complications such as facial palsy or dysgeusia, cholesteatoma, migration of the device, recurrent otitis media, and chronic headaches are among the reported complications [57]. A systematic review of the literature showed that severe complications related to infection leading to mastoiditis and meningitis are very rare when performed by an experienced surgeon [6]. The incidence of disequilibrium is higher in elderly patients aged 75 years or above [8]. Vestibular complications show the highest incidence when regarding delayed complications after cochlear implantation [6]. Overall, cochlear implantation is considered as a safe surgical technique for hearing restoration [5].

Speech understanding among cochlear implant listeners is highly variable and rarely predictable. The quality of the interface between the electrodes and the spiral ganglion neurons is one of the main factors affecting speech understanding [9]. The position of the electrode array within the cochlea and the trauma resulting during electrode insertion strongly influence the nerve-electrode interaction and therefore can affect speech perception [913].

Despite significant advancements in electrode design and surgical implantation techniques, insertion trauma still has the potential to negatively impact hearing outcomes. Direct tissue damage as well as immunological reactions after implantation lead to fibrotic and osteogenic [14] alterations of the scala tympani. The amount of fibrous and osseous tissue is negatively correlated with residual spiral ganglion neuron counts in humans [10]. Temporal bone pathology studies have shown that outcome measures such as word recognition scores depend on the number of residual spiral ganglion neurons [10, 12]. Thus, insertion trauma may affect the outcome of sensory restoration [15] and require higher electrical stimuli for effective neurostimulation [13]. Other negative outcomes of trauma include increased energy consumption and aberrant spread of current resulting in cross-channel interactions [9, 13]. Atrophy of the stria vascularis arising from tissue damage or ageing also can impair implant performance since it influences the health of the organ of Corti and consequently also the state of the neurons to be excited by the cochlear implant [16].

Cells derived from the bone marrow possess the innate capacity to induce repair of traumatised tissue and to modulate immunological reactions [1719]. The microenvironment of bone marrow includes a mixed population of stromal cell types that are possible sources of chemokines, growth factors, and cytokines [20]. Diverse studies have evaluated the use of mesenchymal progenitor or embryonic stem cells [18, 19, 21, 22] and only a few considered hematopoietic progenitor cells for the restoration of the inner ear [22, 23]. However, none of these cells have yet been used in the clinical setting for inner ear therapy. Hematopoietic progenitor cells are able to migrate into the cochlea even after intravenous transplantation of whole bone marrow [22]. This effect has not been observed for mesenchymal progenitor cells (MPC). MPC secrete a variety of neuroprotective growth factors [17] and reduce scarring by downregulation of excessive fibroblast proliferation [24]. The secretome of progenitor cells isolated from the bone marrow can stabilise traumatised tissue [17]. Injuries occur during electrode insertion and are responsible for ossification of the cochlea [14]. Therefore, anti-inflammatory treatment may be crucial for hearing preservation and for the prevention of fibrotic tissue formation [25].

Potentially, this anti-inflammatory treatment could be achieved by delivering autologous progenitor cells along with a cochlear implant. The aim of the present study was to develop a clinically feasible protocol for the generation of a biohybrid electrode using autologous mononuclear cells derived from the bone marrow (BM-MNC). The term BM-MNC includes all cells with unilobulated or rounded nuclei that lack granules in the cytoplasm [26]. Due to their density and size, BM-MNC can be easily separated from myeloid cells and erythrocyte progenitors [26]. They consist of hematopoietic progenitor cells at different stages of maturation [27]. Other cells contributing to the BM-MNC are cells with multipotent capacity such as mesenchymal stromal cells [20, 27], very small embryonic-like stem cells [28, 29], multipotent adult progenitor cells [30], endothelial progenitor cells [31], and tissue-committed stem cells [27]. In addition to the progenitor cells, lymphocytes, plasmatic cells, monocytes, and macrophages also reside in the bone marrow and can be identified in the mononuclear fraction [26]. Due to their capacity to exert neuroprotection, immunomodulation, neurorestoration, and neurogenesis, autologous BM-MNC were transplanted into patients with cerebral palsy and led to a reduction in disability and to an improvement in the quality of life [32]. In addition, a short-term benefit of infusing bone marrow-derived cells into patients with chronic heart failure has been observed, and this effect seems to be related to the secretome of these cells [33]. Thus, BM-MNC have been widely used in human studies as an immune modulator and source of protective growth factors. The goal of the this study was to demonstrate the feasibility and safety of this approach in human cochlear implantation. As part of this study, autologous BM-MNC were attached to cochlear implant electrodes using fibrin glue. For each patient, safety readouts consisted of regular physical examination, impedance measures of the electrode in the implanted ear, and comparison to the contralateral, previously implanted ear. An aliquot of BM-MNC from each patient was used to study persistence of cells on a coated electrode in vitro and to assay their protective qualities.