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Abstract
BackgroundA promising approach to improve the performance of neural implants consists of adding nanomaterials, such as nanowires, to the surface of the implant. Nanostructured interfaces could improve the integration and communication stability, partly through the reduction of the cell-to-electrode distance. However, the safety issues of implanted nanowires in the brain need to be evaluated and understood before nanowires can be used on the surface of implants for long periods of time. To this end we here investigate whether implanted degradable nanowires offer any advantage over non-degradable nanowires in a long-term in vivo study (1 year) with respect to brain tissue responses.ResultsThe tissue response after injection of degradable silicon oxide (SiOx)-coated gallium phosphide nanowires and biostable hafnium oxide-coated GaP nanowires into the rat striatum was compared. One year after nanowire injection, no significant difference in microglial or astrocytic response, as measured by staining for ED1 and glial fibrillary acidic protein, respectively, or in neuronal density, as measured by staining for NeuN, was found between degradable and biostable nanowires. Of the cells investigated, only microglia cells had engulfed the nanowires. The SiOx-coated nanowire residues were primarily seen in aggregated hypertrophic ED1-positive cells, possibly microglial cells that have fused to create multinucleated giant cells. Occasionally, degradable nanowires with an apparently intact shape were found inside single, small ED1-positive cells. The biostable nanowires were found intact in microglia cells of both phenotypes described.ConclusionThe present study shows that the degradable nanowires remain at least partly in the brain over long time periods, i.e. 1 year; however, no obvious bio-safety issues for this degradable nanomaterial could be detected.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0216-7) contains supplementary material, which is available to authorized users.
Highlights
A promising approach to improve the performance of neural implants consists of adding nanomaterials, such as nanowires, to the surface of the implant
In order to test the biocompatibility of nanowires per se, we have recently investigated the brain tissue response to the injection of nanowires in the brain
To determine the impact of degradable vs. biostable nanowire exposure on the brain tissue response, we injected 2 μm long silicon oxide (SiOx)-coated gallium phosphide (GaP) nanowires into rat striatum. This was compared to the tissue response after injection of hafnium oxide (HfOx)-coated 2 μm GaP nanowires
Summary
A promising approach to improve the performance of neural implants consists of adding nanomaterials, such as nanowires, to the surface of the implant. The safety issues of implanted nanowires in the brain need to be evaluated and understood before nanowires can be used on the surface of implants for long periods of time. To this end we here investigate whether implanted degradable nanowires offer any advantage over non-degradable nanowires in a long-term in vivo study (1 year) with respect to brain tissue responses. Micro- and nanostructured electrode surfaces have been suggested to improve recording properties and reduce tissue responses [1,2,3,4,5,6,7]. The degraded nanowire fragments were found engulfed by macrophages/microglia in the injection tract [23], indicating that the nanowire material used could be fragmented or dissolved in the brain tissue but not cleared from the brain after 12 weeks
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