An energy-boosting hydrogel couples magnetoelectrical stimulation and metabolic support for enhanced spinal cord regeneration.

Abstract

Spinal cord injury (SCI) disrupts both neural and vascular networks, leading to a dual deficiency of bioelectric and biochemical energy that severely impedes neuroregeneration. To address this challenge, we developed an energy-boosting hydrogel that integrates biosafe electrical stimulation with a sustained-release biochemical energy system, thereby alleviating energy deficits to promote neural repair. Biodegradable potassium sodium niobate/ferrosoferric oxide (KNN/FO) nanoparticles were synthesized to enable in situ magnetoelectric conversion, and their efficacy in promoting regeneration through electrical stimulation was confirmed in vitro. Transcriptomic and metabolomic analyses further elucidated the synergistic mechanisms between bioelectric and biochemical energy pathways. Based on these findings, phosphocreatine-grafted chitosan (PCr-C) was prepared for sustained biochemical energy release and integrated with KNN/FO nanoparticles into a 3D-printable gelatin-based composite hydrogel (PCr-CGNP). In a rat SCI model, PCr-CGNP successfully achieved dual-energy delivery under a magnetic field and significantly promoted neuroregeneration. This study elucidates the critical role of bioelectric and biochemical energy in post-SCI neuroregeneration and establishes a novel hydrogel-based dual-energy synergistic delivery strategy, providing a theoretical and therapeutic foundation for spinal cord repair.