Nerve-Mimetic Adhesive Hydrogel Electroceuticals: Tailoring In Situ Physically Entangled Domains in Singular Polymers

Implantable electrochemicals stand out as promising candidates for resolving peripheral nerve injuries. However, challenges persist in designing bioelectronic materials that mimic tissue due to modulus matching, conformal adhesion, and immune responses. Herein, we present a nerve-mimicking design rationale for biocompatible hydrogel-based electroceuticals with a tissue-like modulus, robust and conformal tissue adhesion, exceptional mechanical toughness, and efficient stress dissipation. Inspired by the hierarchical structure of the peripheral nerve, the hydrogel substrate features a structurally gradient bilayer transitioning from a dense to a loose polymeric network, utilizing alginate functionalized with either photo-cross-linkable methacrylate or tissue-adhesive phenylborate. Due to the varying water affinity of the tethering groups, a physically entangled interfacial domain is in situ formed during dehydration of the pre-gel film, resulting in enhanced mechanical toughness and strong adhesion. The hydrogel electroceuticals, when integrated with conducting polymeric electrodes, locally stimulate nerve tissue, improving tissue regeneration in a crushed nerve injury model.