Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to...

A consistent feature of the foreign body response (FBR), irrespective of the type of implant, is persistent inflammation at the biotic-abiotic interface signaled by biomarkers of macrophage/microglial activation. Since macrophage-secreted factors shape the foreign body reaction, implant designs that reduce macrophage activation should improve biocompatibility and, with regard to recording devices, should improve reliability and longevity. At present, it is unclear whether the goal of seamless integration is possible or whether electrode developers can modulate specific aspects of the FBR by intentionally manipulating the constitutive properties of the implant. To explore this area, we studied the chronic brain FBR to planar solid silicon microelectrode arrays and planar lattice arrays with identical penetrating profiles but with reduced surface area in rats after an 8-week indwelling period. Using quantitative immunohistochemistry, we found that presenting less surface area after equivalent iatrogenic injury is accompanied by significantly less persistent macrophage activation, decreased blood brain barrier leakiness, and reduced neuronal cell loss. Our findings show that it is possible for implant developers to modulate specific aspects of the FBR by intentionally manipulating the constitutive properties of the implant. Our results also support the theory that the FBR to implanted electrode arrays, and likely other implants, can be explained by the presence of macrophages at the biotic-abiotic interface, which act as a sustained delivery source of bioactive agents that diffuse into the adjacent tissue and shape various features of the brain FBR. Further, our findings suggest that one method to improve the recording consistency and lifetime of implanted microelectrode arrays is to design implants that reduce the amount of macrophage activation at the biotic-abiotic interface and/or enhance the clearance or impact of their released factors.