Objective:
Good performance with the cochlear implant (CI) depends essentially on a high number of spiral ganglion neurons (SGN). Treatment with growth factors such as brain-derived neurotrophic factor (BDNF) can support the survival of SGN. Up to now, a clinically feasible approach to deliver such factors to the inner ear, particularly for long-term, is still lacking. Therefore, alginate hydrogel was investigated as release matrix for BDNF as CI-coating or in bead form and the neuroprotective effect of harvested supernatant was analyzed.
Methods:
Alginate sol was mixed in equal parts with BDNF-solution (100 µg/ml for coating, 10 µg/ml for bead) (Alg-BDNF) or with plain solution as negative control (Alg-NC). This mix was applied as coating to a CI-electrode dummy (~50 µl) or beads (10 µl) were formed by ionic gelation with BaCl2. Release of BDNF was conducted in artificial perilymph at 37°C, with daily (first week), and weekly full replacement of the medium and microscopic documentation of the gel shape. Stability of the gel was analyzed using the microscopic images, released BDNF-amount was detected by ELISA and the neuroprotective effect of the supernatant was tested in culture of murine SGN.
Results:
Crosslinking and stability of the alginate gel was not negatively affected by mixing with the BDNF-solution. BDNF was released in decreasing concentrations, from the alginate-coating observed over three month (about 230-5 ng/ml) and from the alginate-beads over three weeks (about 1-0.3 ng/ml). In the SGN culture, the Alg-BDNF supernatant showed a significant neuroprotective effect with about 25-10% survival rate until day 35 of release, when compared to a factor-free control (6%). In addition, this effect was similar to the standard control including 50 ng/ml BDNF (17%).
Conclusion:
The results of the performed study indicate that alginate is a very promising matrix for delivery of BDNF. Both the use as CI-coating and as potentially implantable beads seem feasible and offer an opportunity for a neuroprotective treatment of the CI-implanted inner ear.

**Objective:**
Good performance with the cochlear implant (CI) depends essentially on a high number of spiral ganglion neurons (SGN). Treatment with growth factors such as brain-derived neurotrophic factor (BDNF) can support the survival of SGN. Up to now, a clinically feasible approach to deliver such factors to the inner ear, particularly for long-term, is still lacking. Therefore, alginate hydrogel was investigated as release matrix for BDNF as CI-coating or in bead form and the neuroprotective effect of harvested supernatant was analyzed.
**Methods:**
Alginate sol was mixed in equal parts with BDNF-solution (100 µg/ml for coating, 10 µg/ml for bead) (Alg-BDNF) or with plain solution as negative control (Alg-NC). This mix was applied as coating to a CI-electrode dummy (~50 µl) or beads (10 µl) were formed by ionic gelation with BaCl2. Release of BDNF was conducted in artificial perilymph at 37°C, with daily (first week), and weekly full replacement of the medium and microscopic documentation of the gel shape. Stability of the gel was analyzed using the microscopic images, released BDNF-amount was detected by ELISA and the neuroprotective effect of the supernatant was tested in culture of murine SGN.
**Results:**
Crosslinking and stability of the alginate gel was not negatively affected by mixing with the BDNF-solution. BDNF was released in decreasing concentrations, from the alginate-coating observed over three month (about 230-5 ng/ml) and from the alginate-beads over three weeks (about 1-0.3 ng/ml). In the SGN culture, the Alg-BDNF supernatant showed a significant neuroprotective effect with about 25-10% survival rate until day 35 of release, when compared to a factor-free control (6%). In addition, this effect was similar to the standard control including 50 ng/ml BDNF (17%).
**Conclusion:**
The results of the performed study indicate that alginate is a very promising matrix for delivery of BDNF. Both the use as CI-coating and as potentially implantable beads seem feasible and offer an opportunity for a neuroprotective treatment of the CI-implanted inner ear.

BDNF-delivery by alginate hydrogel is a promising tool for neuroprotection in the CI-treated inner ear

It is with great pleasure and enthusiasm, that on behalf of the Cochlear Implant centers of the Radboud UMC in Nijmegen and Erasmus MC Sophia Children’s Hospital in Rotterdam to invite you to attend the 16th European Symposium on Pediatric Cochlear Implantation to Rotterdam, the Netherlands in 2023.

Yours sincerely, on behalf of the CI Centers at Radboud UMC and Erasmus MC,