Objective:
The cochlear implant (CI) outcome might be improved, amongst others, by protection
of spiral ganglion neurons (SGN) through a chronical application of neurotrophic factors
like BDNF (brain-derived neurotrophic factor). Genetically modified cells, encapsulated
in alginate to avoid migration or rejection, implanted as a CI-coating, may be a feasible
drug delivery system.
Methods:
Bone marrow-derived human mesenchymal stem cells (MSCs) were expanded, genetically
modified for BDNF-production and encapsulated in alginate. To study the neuroprotective
effect, beads were formed of the alginate-MSC-matrix and co-cultivated for 48h with
dissociated SGN. The bead stability was macroscopically verified and the BDNF-amount
in the pooled supernatant was analyzed by ELISA-detection. The survival rate of the
SGN is evaluated after fixation and neuron-specific immunocytochemistry.
By dip coating the matrix is linked to CI-electrode models. The stability of this
coating is tested by repeated insertion of the CI-electrode models in an artificial
cochlea model followed by microscopic control for abrasion.
Results:
The formed beads are stable in culture, BDNF is produced (pg-range) and the SGN are
significantly protected against degeneration. By dip coating the matrix is linkable
to the CI-electrode and the degree of abrasion is low after first insertion but increased
by multiple repetitions.
Conclusions:
Alginate-encapsulated, BDNF-producing MSCs coated on CI-electrodes are a promising
system for chronical drug delivery. Further investigations have to concentrate on
lifespan and maintenance of BDNF-production of the MSCs and an automation of the coating-process.
