Abstract

Neural interface technologies including recording and stimulation electrodes are currently in the early phase of clinical trials aiming to help patients with spinal cord injuries, degenerative disorders, strokes interrupting descending motor pathways, or limb amputations. Their lifetime is of key importance; however, it is limited by the foreign body response of the tissue causing the loss of neurons and a reactive astrogliosis around the implant surface. Improving the biocompatibility of implant surfaces, especially promoting neuronal attachment and regeneration is therefore essential. In our work, bioactive properties of implanted black polySi nanostructured surfaces (520–800 nm long nanopillars with a diameter of 150–200 nm) were investigated and compared to microstructured Si surfaces in eight-week-long in vivo experiments. Glial encapsulation and local neuronal cell loss were characterised using GFAP and NeuN immunostaining respectively, followed by systematic image analysis. Regarding the severity of gliosis, no significant difference was observed in the vicinity of the different implant surfaces, however, the number of surviving neurons close to the nanostructured surface was higher than that of the microstructured ones. Our results imply that the functionality of implanted microelectrodes covered by Si nanopillars may lead to improved long-term recordings.

Highlights

  • Neural interface technologies are currently being introduced in preclinical applications aiming for the treatment of patients with spinal cord injuries[1], degenerative disorders[2], brainstem strokes[3], amyotrophic lateral sclerosis[4], tetraplegia[5] and/or limb amputation(s)[6]

  • The heights of the nanopillars were between 520–800 nm and their density was between 18–70 pillars/μm[2] depending on the fabrication parameters of the deep reactive ion etching (DRIE) process[32]

  • At larger distance from the implantation site, we found that GFAP staining was consistently lower in the case of the nanostructured Si surfaces compared to the others, it was significant only in the case of the microstructured fluorocarbon surfaces up to a distance of 350 μm from the track

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Summary

Introduction

Neural interface technologies are currently being introduced in preclinical applications aiming for the treatment of patients with spinal cord injuries[1], degenerative disorders[2], brainstem strokes[3], amyotrophic lateral sclerosis[4], tetraplegia[5] and/or limb amputation(s)[6]. The immune response around the neural implant can modify the appropriate interpretation of in vivo recordings[8], since it leads to reduced sensitivity, stability and very often to device failure. Several groups have investigated the effect of nanostructuring on neurons and glial cells in vitro aiming for enhanced in vivo neural implant efficiency. Of the nanostructured samples, several groups published better neuronal cell adhesion and viability on nanostructured surfaces compared to the smooth references in the past few years[16,25,26,27]. Turner and colleagues investigated the attachment of immortalised- and primary astroglial cells on nanostructured surfaces in the same experiment, but ended up with contradictory results[14]. In the work of Fan et al, primary rat neuronal cells were observed to migrate to nanostructured areas of their samples[16]

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