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

Abstract

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.

Tissue-like Neural Probes for Understanding and Modulating the Brain

“…15,30,33,35 Confocal fluorescence images of probe-containing brain slices at 2 weeks, 4 weeks and 3 months (Figure 2A–C) revealed several unique features. First, the mesh electronics produced little inflammation at short times (2 weeks) post-implantation, evidenced by only a slight accumulation of astrocytes and microglia signals near the mesh boundary, while there was essentially no evidence for a chronic immune response at longer times.…”

Harnessing the Potential of Biomaterials for Brain Repair after Stroke

“…This approach has been proposed for in vivo use through externally applied electric fields to increase and direct the migration of endogenous NSPCs, though it could also be used to direct the migration of transplanted stem cells to prevent their clustering (Iwasa et al, 2017). Recent advances in electrically conductive materials may aid in scaling this approach to larger human brains where sufficient electrical fields may be difficult to generate or more spatially defined electrical fields may be desired (Zhou et al, 2017).…”

Recent advances in neural electrode–tissue interfaces

“…Many of these difficulties are handled by coatings such as silk [75, 76] and carboxymethyl cellulose [77], or shuttles [69, 78, 79], syringe injection [80] and magnetic insertion [81]. Materials that are stiff at room temperature and soften after implantation in the brain are another interesting strategy [82, 83], however, these materials tend to absorb water in vivo , which challenges the insulation.…”

“…(C) Bed of needles (Utah) array [112], copyright 1998 Elsevier. (D) Syringe injectable mesh electrode [80], copyright 2017 National Academy of Sciences. (E) Carbon fiber electrode [47], copyright 2012 Nature Publishing.…”