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Histological evaluation of flexible neural implants; Flexibility limit for reducing the tissue response?

Lee, Heui Chang; Ejserholm, Fredrik LU ; Gaire, Janak; Currlin, Seth; Schouenborg, Jens LU ; Wallman, Lars LU ; Bengtsson, Martin LU ; Park, Kinam and Otto, Kevin J. (2017) In Journal of Neural Engineering 14(3).
Abstract

Objective. Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? Approach. Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (∼150 GPa), polyimide (1.5 GPa), OSTE+Hard... (More)

Objective. Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? Approach. Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (∼150 GPa), polyimide (1.5 GPa), OSTE+Hard (300 MPa), and OSTE+Soft (6 MPa). Main results. We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. Significance. The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chronic neural implant, flexible brain-computer interface (fBCI), foreign body response (FBR), neuroprosthetics, off-stoichiometry thiol-enes (OSTE)
in
Journal of Neural Engineering
volume
14
issue
3
publisher
IOP Publishing
external identifiers
  • scopus:85020424340
  • wos:000400978100001
ISSN
1741-2560
DOI
10.1088/1741-2552/aa68f0
language
English
LU publication?
yes
id
b6b82011-f8a7-4b75-8ce4-143febb87749
date added to LUP
2017-06-28 10:56:17
date last changed
2018-04-29 04:40:09
@article{b6b82011-f8a7-4b75-8ce4-143febb87749,
  abstract     = {<p>Objective. Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain's micromotion. However, a large discrepancy of Young's modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? Approach. Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (∼150 GPa), polyimide (1.5 GPa), OSTE+<sub>Hard</sub> (300 MPa), and OSTE+<sub>Soft</sub> (6 MPa). Main results. We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. Significance. The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.</p>},
  articleno    = {036026},
  author       = {Lee, Heui Chang and Ejserholm, Fredrik and Gaire, Janak and Currlin, Seth and Schouenborg, Jens and Wallman, Lars and Bengtsson, Martin and Park, Kinam and Otto, Kevin J.},
  issn         = {1741-2560},
  keyword      = {chronic neural implant,flexible brain-computer interface (fBCI),foreign body response (FBR),neuroprosthetics,off-stoichiometry thiol-enes (OSTE)},
  language     = {eng},
  month        = {05},
  number       = {3},
  publisher    = {IOP Publishing},
  series       = {Journal of Neural Engineering},
  title        = {Histological evaluation of flexible neural implants; Flexibility limit for reducing the tissue response?},
  url          = {http://dx.doi.org/10.1088/1741-2552/aa68f0},
  volume       = {14},
  year         = {2017},
}