Multi-ionic, super-adhesive, low-swelling, and antioxidative hydrogel for spinal cord injury repair

Spinal cord injury (SCI) often leads to severe and long-lasting disability, profoundly impacting both the physical and mental well-being of patients. While rehabilitation and regenerative medicine represent promising avenues for SCI recovery, their combined application remains underexplored. In this study, we developed a biodegradable, low-swelling, multi-ionic hydrogel composed of oxidized dextran (ODex), dopamine-grafted gelatin (DG), and a combination of essential ions (Ca 2+ , Mg 2+ , Zn 2+ , and Fe 3+ ). This hydrogel exhibits a suite of desirable properties, including optimal pore size, excellent biocompatibility, injectability, minimal swelling, strong adhesiveness, and notable antioxidative capacity. Functionally, the hydrogel can block calcium channels, reduce neuronal excitability, and alleviate muscle stiffness. At the cellular level, it supports neuronal growth and enhances antioxidative defense mechanisms. Behavioral assessments and electrophysiological studies in animals demonstrated that the multi-ionic hydrogel promotes the generation of new neurons, axonal regeneration, synaptogenesis of various neurotransmitters, and supports remyelination. The results showed significant functional recovery in rodents, particularly in motor and sensory functions, with remarkable improvement in urinary retention. This study suggests that multi-ionic hydrogels hold great potential as a strategy for spinal cord injury repair and neural regeneration, and may also provide hope for tissue regeneration in other medical conditions.