Ultrastructural Analysis of Neuroimplant-Parenchyma Interfaces Uncover Remarkable Neuroregeneration Along-With Barriers That Limit the Implant Electrophysiological Functions

Aviv Sharon; Nava Shmoel; Hadas Erez; Maciej M Jankowski; Yael Friedmann; Micha E Spira

doi:10.3389/fnins.2021.764448

Ultrastructural Analysis of Neuroimplant-Parenchyma Interfaces Uncover Remarkable Neuroregeneration Along-With Barriers That Limit the Implant Electrophysiological Functions

Front Neurosci. 2021 Nov 22:15:764448. doi: 10.3389/fnins.2021.764448. eCollection 2021.

Authors

Aviv Sharon^{1

2}, Nava Shmoel^{1

3}, Hadas Erez^{1

2}, Maciej M Jankowski^{2

4}, Yael Friedmann⁵, Micha E Spira^{1

2

3}

Affiliations

¹ Department of Neurobiology, The Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem, Israel.
² The Charles E. Smith Family and Prof. Joel Elkes Laboratory for Collaborative Research in Psychobiology, The Hebrew University of Jerusalem, Jerusalem, Israel.
³ The Harvey M. Kruger Family Center for Nanoscience, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁴ Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁵ Bio-Imaging Unit, The Alexander Silberman Institute of Life Science the Hebrew University of Jerusalem, Jerusalem, Israel.

Abstract

Despite increasing use of in vivo multielectrode array (MEA) implants for basic research and medical applications, the critical structural interfaces formed between the implants and the brain parenchyma, remain elusive. Prevailing view assumes that formation of multicellular inflammatory encapsulating-scar around the implants [the foreign body response (FBR)] degrades the implant electrophysiological functions. Using gold mushroom shaped microelectrodes (gMμEs) based perforated polyimide MEA platforms (PPMPs) that in contrast to standard probes can be thin sectioned along with the interfacing parenchyma; we examined here for the first time the interfaces formed between brains parenchyma and implanted 3D vertical microelectrode platforms at the ultrastructural level. Our study demonstrates remarkable regenerative processes including neuritogenesis, axon myelination, synapse formation and capillaries regrowth in contact and around the implant. In parallel, we document that individual microglia adhere tightly and engulf the gMμEs. Modeling of the formed microglia-electrode junctions suggest that this configuration suffice to account for the low and deteriorating recording qualities of in vivo MEA implants. These observations help define the anticipated hurdles to adapting the advantageous 3D in vitro vertical-electrode technologies to in vivo settings, and suggest that improving the recording qualities and durability of planar or 3D in vivo electrode implants will require developing approaches to eliminate the insulating microglia junctions.

Keywords: immunohistology; interfacing; microelectrodes; neural-engineering; neuroelectronics; neuroimplant; polyimide; ultrastructure (electron microscopy).