Abstract
Spinal cord injury (SCI) compromises the electrophysiological properties of tissues and disrupts the electrical transmission pathways, ultimately resulting in motor dysfunction and neurogenic bladder impairment. Therefore, restoration of normal electrophysiological functions in injured spinal cord tissues is crucial for SCI rehabilitation. Electrical stimulation (ES) exhibits therapeutic potential for neurological disorders via neuronal modulation, showing enhanced efficacy in combination with traditional Chinese medicine practices, such as targeted acupuncture. Specifically, acupuncture at Huatuo-Jiaji acupoints, located bilaterally along the vertebral column, exerts neurological regulatory effects. In this study, we developed a dual-modality therapeutic approach combining implantable biomimetic conductive hydrogels for internal ES with electroacupuncture at Huatuo-Jiaji acupoints for external ES to reconstruct the neural electrical microenvironment and synergistically enhance the electrophysiological recovery post-SCI. The engineered conductive hydrogels, fabricated by incorporating carbon nanotubes into photocrosslinkable gelatin matrices, showed dual functionality by facilitating endogenous electrical signal propagation and enhancing the exogenous ES efficacy. This combination therapy significantly attenuated the inflammatory responses and glial scar formation, concurrently promoting axonal regeneration and mitigating demyelination. Functional assessments revealed substantial improvements in both locomotor recovery and neurogenic bladder control in complete spinal cord transection model rats. Mechanistic investigations revealed the downregulation of the Janus kinase-signal transducer and activator of transcription signaling pathway as a key regulator of anti-inflammatory effects of the combination treatment. Overall, our innovative internal-external ES integration strategy offers a promising translational approach for SCI repair by simultaneously enhancing neural regeneration and facilitating functional restoration.