Evaluating the in vivo glial response to miniaturized parylene cortical probes coated with an ultra-fast degrading polymer to aid insertion

J Neural Eng. 2018 Jun;15(3):036002. doi: 10.1088/1741-2552/aa9fad. Epub 2018 Feb 27.

Abstract

Objective: Despite the feasibility of short-term neural recordings using implantable microelectrodes, attaining reliable, chronic recordings remains a challenge. Most neural recording devices suffer from a long-term tissue response, including gliosis, at the device-tissue interface. It was hypothesized that smaller, more flexible intracortical probes would limit gliosis by providing a better mechanical match with surrounding tissue.

Approach: This paper describes the in vivo evaluation of flexible parylene microprobes designed to improve the interface with the adjacent neural tissue to limit gliosis and thereby allow for improved recording longevity. The probes were coated with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)) polymer that provides temporary mechanical support for device implantation, yet degrades within 2 h post-implantation. A parametric study of probes of varying dimensions and polymer coating thicknesses were implanted in rat brains. The glial tissue response and neuronal loss were assessed from 72 h to 24 weeks post-implantation via immunohistochemistry.

Main results: Experimental results suggest that both probe and polymer coating sizes affect the extent of gliosis. When an appropriate sized coating dimension (100 µm × 100 µm) and small probe (30 µm × 5 µm) was implanted, a minimal post-implantation glial response was observed. No discernible gliosis was detected when compared to tissue where a sham control consisting of a solid degradable polymer shuttle of the same dimensions was inserted. A larger polymer coating (200 µm × 200 µm) device induced a more severe glial response at later time points, suggesting that the initial insertion trauma can affect gliosis even when the polymer shuttle degrades rapidly. A larger degree of gliosis was also observed when comparing a larger sized probe (80 µm × 5 µm) to a smaller probe (30 µm × 5 µm) using the same polymer coating size (100 µm × 100 µm). There was no significant neuronal loss around the implantation sites for most device candidates except the group with largest polymer coating and probe sizes.

Significance: These results suggest that: (1) the degree of mechanical trauma at device implantation and mechanical mismatches at the probe-tissue interface affect long term gliosis; (2) smaller, more flexible probes may minimize the glial response to provide improved tissue biocompatibility when used for chronic neural signal recording; and (3) some degree of glial scarring did not significantly affect neuronal distribution around the probe.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants / adverse effects
  • Absorbable Implants / trends*
  • Animals
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / surgery
  • Electrodes, Implanted / adverse effects
  • Electrodes, Implanted / standards
  • Electrodes, Implanted / trends*
  • Male
  • Microelectrodes / adverse effects
  • Microelectrodes / standards
  • Microelectrodes / trends
  • Neuroglia / metabolism*
  • Polymers / chemical synthesis
  • Polymers / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Xylenes / chemical synthesis
  • Xylenes / metabolism*

Substances

  • Polymers
  • Xylenes
  • parylene