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

Abstract

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. 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. 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. 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. This study demonstrates UHV-alginate to be a suitable scaffold for BDNF-producing fibroblasts. UHV-alginates are a promising biomaterial for cochlear implant biofunctionalization.