The Safety of Micro-Implants for the Brain

Abstract

Technological advancements in electronics and micromachining now allow the development of discrete wireless brain implantable micro-devices. Applications of such devices include stimulation or sensing and could enable direct placement near regions of interest within the brain without the need for electrode leads or separate battery compartments that are at increased risk of breakage and infection. Clinical use of leadless brain implants is accompanied by novel risks, such as migration of the implant. Additionally, the encapsulation material of the implants plays an important role in mitigating unwanted tissue reactions. These risks have the potential to cause harm or reduce the service of life of the implant. In the present study, we have assessed post-implantation tissue reaction and migration of borosilicate glass-encapsulated micro-implants within the cortex of the brain. Twenty borosilicate glass-encapsulated devices (2 × 3.5 × 20 mm) were implanted into the parenchyma of 10 sheep for 6 months. Radiographs were taken directly post-surgery and at 3 and 6 months. Subsequently, sheep were euthanized, and GFAP and IBA-1 histological analysis was performed. The migration of the implants was tracked by reference to two stainless steel screws placed in the skull. We found no significant difference in fluoroscopy intensity of GFAP and a small difference in IBA-1 between implanted tissue and control. There was no glial scar formation found at the site of the implant's track wall. Furthermore, we observed movement of up to 4.6 mm in a subset of implants in the first 3 months of implantation and no movement in any implant during the 3-6-month period of implantation. Subsequent histological analysis revealed no evidence of a migration track or tissue damage. We conclude that the implantation of this discrete micro-implant within the brain does not present additional risk due to migration.

Keywords: brain implant; implant migration; micro-implant; micro-implant GFAP; micro-implant IBA-1; micro-implant safety; microdevice.

FIGURE 1

Burr holes’ location and subsequent lateral radiograph. (A) Positioning of burr holes and implant location in reference to the skull’s sutures. (B) Example lateral radiograph produced from the implant locations.

FIGURE 2

Reference origin used to calculate displacement. Origin created using two screw’s lodged in the sheep’s skull, used to track the location of the centroid of each implant between radiographs.

FIGURE 3

GFAP and IBA-1 expression as a function of area: (A) GFAP expression (measured as total mean gray value per mm²) from the implanted samples compared to an equivalent area from an un-implanted region of sheep brain. While GFAP was slightly decreased in the implanted tissue, this difference was not significant (p < 0.1131). The same measurements were made to assess the expression of IBA-1 in implanted tissue and an equivalent area from and un-implanted region (B). There was a small, significant increase in the implanted tissue compared to un-implanted control (p < 0.0419). * Indicates a statistically significant difference.

FIGURE 4

Comparison of morphological changes of astrocytes and microglia adjacent to the implant track and un-implanted tissue. 20X Magnification. (A) Astrocytes adjacent to the implant track assumed directionality and processes were diminished in contrast to un-implanted tissue (C), where astrocytes displaced their classic, stellate morphology with numerous processes extending in all directions of the microenvironment. Like astrocytes in implanted tissue, microglia also assumed directionality and processes appeared thicker (B), indicated an activated phenotype compared to their quiescent state in the absence of trauma (D), where microglia assume a rounded morphology with thin, stellate-like processes.

FIGURE 5

10X Magnification of implant track. Lack of a visible glial scar at the tissue-implant interface necessitated a different approach to analysis. At the tissue-implant interface, there was no discernible visible scar tissue to measure, necessitating the measurement of fluorescence intensity from a given area either side of the implant track, supplemented with morphological analysis.

FIGURE 6

Section of brain tissue displaying the implant piercing the ventricle wall. Dissection of brain tissue following the sacrifice of the sheep outlining the piercing of the ventricle wall by an implant.