Implantable Multi-Cross-Linked Membrane-Ionogel Assembly for Reversible Non-Faradaic Neurostimulation

Abstract

Neural interfaces play a major role in modulating neuralsignalsfor therapeutic purposes. To meet the demand of conformable neuralinterfaces for developing bioelectronic medicine, recent studies havefocused on the performance of electrical neurostimulators employingsoft conductors such as conducting polymers and electronic or ionicconductive hydrogels. However, faradaic charge injection at the interfaceof the electrode and nerve tissue causes irreversible gas evolution,oxidation of electrodes, and reduction of biological ions, thus causingundesired tissue damage and electrode degradation. Here we reporta conformable neural interface engineering based on multicross-linkedmembrane-ionogel assembly (termed McMiA), which enables nonfaradaicneurostimulation without irreversible charge transfer reaction. TheMcMiA consists of a genipin-cross-linked biopolymeric ionogel coupledwith a dopamine-cross-linked graphene oxide membrane to prevent ionexchange between biological and synthetic McMiA ions and to functionas a bioadhesive forming covalent bonds with the target tissues. Inaddition, the demonstration of bioelectronic medicine via the McMiA-basedneurostimulation of sciatic nerves shows the enhanced clinical utilityin treating the overactive bladder syndrome. As the McMiA-based neuralinterface is soft, robust for bioadhesion, and stable in a physiologicalenvironment, it can offer significant advancement in biocompatibilityand long-term operability for neural interface engineering.