UHV-alginate as matrix for neurotrophic factor producing cells - a novel biomaterial for cochlear implant optimization to preserve inner ear neurons from degeneration

Hypothesis: Ultra high viscous (UHV-) alginate is a suitable matrix for brain-derived neurotrophic factor (BDNF) producing cells, enabling cell survival and BDNF release out of the matrix and subsequent protection of auditory neuronal cells. Background: Cochlear implant (CI) target cells, spiral ganglion cells (SGC), undergo a progressive degeneration. BDNF prevents SGC from degeneration but has to be delivered locally to the inner ear for months. A permanent growth factor application may be realized via a cell-based drug delivery system. Encapsulation of this delivery system into a matrix could avoid immune response of the recipient, migration, and uncontrolled proliferation of the cells. Methods: NIH3T3-fibroblasts producing endogenous BDNF were incorporated in UHV-alginate. The survival of the cells in the alginate was examined by cell counts of cryogenic slices, and the BDNF production was determined by performing ELISA. The supernatant of the alginate-cell culture was added to primary SGC culture, and the neuroprotective effect of the produced BDNF was observed performing SGC counts. Results: BDNF-producing cells cultivated in UHV-alginate survived for up to 30 days, which was the latest time point observed. The BDNF concentration in cell culture medium, produced from in UHV-alginate incorporated fibroblasts and released out of the alginate matrix into the medium, was significantly increased after 30 days of cultivation. Supernatant of 7 days incubated UHV-alginate containing NIH3T3/BDNF cells significantly increased the SGC survival in vitro. Conclusion: This study demonstrates UHV-alginate to be a suitable scaffold for BDNF-producing fibroblasts. UHV-alginates are a promising biomaterial for cochlear implant biofunctionalization.