Developing an NT3-loaded exosomal biodegradable conductive hydrogel combined with EA for targeted treatment of spinal cord injury.

Spinal cord injury (SCI) causes permanent sensory and motor function loss below the injury site, with limited treatment options. Conductive hydrogels have shown promise for SCI repair due to their electrical and mechanical properties, while neurotrophic factors and extracellular vesicles exhibit anti-inflammatory and neurorestorative effects. This study developed a dual-loaded conductive hydrogel (Exo-N/NT3@ICH) containing both neurotrophic factors and extracellular vesicles and evaluated its efficacy combined with electroacupuncture (EA) for SCI treatment. The hydrogel was synthesized through Schiff base reactions using oxidized hyaluronic acid and aniline trimer, creating a physically crosslinked, injectable conductive matrix. Assessments examined the hydrogel's morphology, mechanical and electrical properties, swelling, degradation, drug release, and electrochemical behaviour. In vitro and in vivo studies further investigated its biocompatibility, anti-inflammatory effects, and pro-angiogenic potential. Results showed that Exo-N/NT3@ICH enhanced cell proliferation and differentiation through its conductivity, controlled release, and antioxidant properties. In a rat SCI model, the hydrogel improved functional outcomes, attributed to its neurotrophic and neuroregenerative effects. This study highlights Exo-N/NT3@ICH, when combined with EA, as a potential injectable therapeutic system to promote neurogenesis and tissue regeneration after SCI.