Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

Significance Seamless integration of electrical probes within neural tissue could substantially enhance their impact and open up new opportunities in neuroscience research through electronic therapeutics. This paper describes systematic studies of brain tissue behavior following implantation of a design for probes that can be precisely targeted to specific brain regions by syringe injection as in many biological species and have an ultraflexible open mesh structure similar to brain tissue itself. Studies of the chronic tissue response postimplantation demonstrate that these tissue-like probes do not elicit inflammation or scarring, in contrast to more conventional probes. Moreover, neurons were found to penetrate through the probes’ open mesh structure, thus demonstrating an unprecedented level of integration and compatibility with the brain circuitry. Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

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