Ultrasound-activated conductive-piezoelectric hydrogel remodels inflammatory and bioelectrical microenvironments for spinal cord injury repair.

Abstract

Disrupted electrical signal conduction and excessive local inflammation following spinal cord injury (SCI) form an inhibitory microenvironment that severely impedes neural regeneration. Here, we developed a multifunctional hydrogel platform (GO-EM/Ba) that integrates ultrasound-triggered wireless electrical stimulation with inflammatory modulation for SCI therapy. The system comprises a methacrylated gelatin/oxidized dextran dual-network scaffold loaded with BaTiO3@PDA@PPy and EGCG-Met nanoparticles. The BaTiO3@PDA@PPy nanoparticles endowed the hydrogel with both piezoelectric and conductive properties. Upon non-invasive ultrasound stimulation, the integrated piezoelectric-conductive architecture enabled localized electrical signal generation by BaTiO3 and facilitated signal transmission through PPy, thereby providing a remotely activated electroactive microenvironment at the injury site. The EGCG-Met nanoparticles were released from the hydrogel in a pH-responsive manner, exerting anti-inflammatory effects. This platform exhibited a storage modulus similar to that of spinal cord tissue, favorable injectability, and suitable conductivity while generating piezoelectric output upon ultrasound activation. In addition, the platform demonstrated good cytocompatibility and antioxidant activity, promoting HT-22 cell growth under ultrasound stimulation and macrophage polarization toward the M2 phenotype. In vivo, GO-EM/Ba significantly promoted motor recovery, reduced inflammation, inhibited glial scar formation, and promoted neural regeneration in SCI rats.

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