Nerve-Mimetic Adhesive\nHydrogel Electroceuticals:\nTailoring In Situ Physically Entangled Domains in Singular Polymers

Implantable\nelectrochemicals stand out as promising candidates\nfor resolving peripheral nerve injuries. However, challenges persist\nin designing bioelectronic materials that mimic tissue due to modulus\nmatching, conformal adhesion, and immune responses. Herein, we present\na nerve-mimicking design rationale for biocompatible hydrogel-based\nelectroceuticals with a tissue-like modulus, robust and conformal\ntissue adhesion, exceptional mechanical toughness, and efficient stress\ndissipation. Inspired by the hierarchical structure of the peripheral\nnerve, the hydrogel substrate features a structurally gradient bilayer\ntransitioning from a dense to a loose polymeric network, utilizing\nalginate functionalized with either photo-cross-linkable methacrylate\nor tissue-adhesive phenylborate. Due to the varying water affinity\nof the tethering groups, a physically entangled interfacial domain\nis in situ formed during dehydration of the pre-gel film, resulting\nin enhanced mechanical toughness and strong adhesion. The hydrogel\nelectroceuticals, when integrated with conducting polymeric electrodes,\nlocally stimulate nerve tissue, improving tissue regeneration in a\ncrushed nerve injury model.