Long-term delivery of brain-derived neurotrophic factor (BDNF) from nanoporous silica nanoparticles improves the survival of spiral ganglion neurons in vitro

Abstract

Sensorineural hearing loss (SNHL) can be overcome by electrical stimulation of spiral ganglion neurons (SGNs) via a cochlear implant (CI). Restricted CI performance results from the spatial gap between the SGNs and the electrode, but the efficacy of CI is also limited by the degeneration of SGNs as one consequence of SHNL. In the healthy cochlea, the survival of SGNs is assured by endogenous neurotrophic support. Several applications of exogenous neurotrophic supply have been shown to reduce SGN degeneration in vitro and in vivo. In the present study, nanoporous silica nanoparticles (NPSNPs), with an approximate diameter of <100 nm, were loaded with the brain-derived neurotrophic factor (BDNF) to test their efficacy as long-term delivery system for neurotrophins. The neurotrophic factor was released constantly from the NPSNPs over a release period of 80 days when the surface of the nanoparticles had been modified with amino groups. Cell culture investigations with NIH3T3 fibroblasts attest a good general cytocompatibility of the NPSNPs. In vitro experiments with SGNs indicate a significantly higher survival rate of SGNs in cell cultures that contained BDNF-loaded nanoparticles compared to the control culture with unloaded NPSNPs (p<0.001). Importantly, also the amounts of BDNF released up to a time period of 39 days increased the survival rate of SGNs. Thus, NPSNPs carrying BDNF are suitable for the treatment of inner ear disease and for the protection and the support of SGNs. Their nanoscale nature and the fact that a direct contact of the nanoparticles and the SGNs is not necessary for neuroprotective effects, should allow for the facile preparation of nanocomposites, e.g., with biocompatible polymers, to install coatings on implants for the realization of implant-based growth factor delivery systems.

BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro

“…The positive control used within our study is 50 ng/ml recombinant human BDNF. This is a concentration of human recombinant BDNF already presented to significantly increase the SGN survival rate compared to relevant controls (Schmidt et al, ; Schulze et al, ; Schwieger et al, ; Wefstaedt et al, ). An additional substitution of the native hMSC supernatant with 50 ng/ml recombinant BDNF could further increase the neuroprotective effect of the hMSCs.…”

In vitro and in vivo accumulation of magnetic nanoporous silica nanoparticles on implant materials with different magnetic properties

“…These materials combine the advantages of an excellent biocompatibility, high specific surface areas, large pore volumes and adjustable pore sizes with narrow pore size distributions as well as facile chemical modification using silanization reactions. Thus, they have a great potential for loading with drugs, proteins or growth factors [ 10 , 37 , 38 ]. As presented in the TEM image the MNPSNPs were spherical core–shell nanoparticles with Fe 3 O 4 as core material and main particles sizes of approximately 110 nm.…”

<p>Mesenchymal stem cell therapy assisted by nanotechnology: a possible combinational treatment for brain tumor and central nerve regeneration</p>

“…170 BDNF-loaded silica nanoparticles support the survival of spiral ganglion neurons in vitro. 171 Likewise, iron oxide nanoparticlesconjugated NGF, glial cell-derived neurotrophic factor, and basic FGF-2 are not only stable but also show improved nerve regeneration compared to free neurotrophic factors on organotypic dorsal root ganglion. In in vivo studies, bilaterally injected silica-DNA complex successfully triggered neurogenesis of neuronal stem/ progenitor cells via stimulation of FGF Receptor 1 signaling pathway.…”