Chronic neurostimulation of splenic nerve enabled by hydrogel-bioelectronics for wireless electroceutical immunomodulation therapy

ABSTRACT Targeted modulation of the splenic nerve offers a selective alternative to vagus nerve stimulation, avoiding off-target activation of mixed vagal fibers. However, the small diameter and anatomical complexity of the splenic nerve pose great challenges for stable neural interfacing. Here, we report a splenic nerve wireless stimulator (SpNWS) built from stretchable and highly conductive hydrogel for chronic electroceutical immunomodulation therapy. The hydrogel-fiber neural electrodes conform to the geometries of splenic neurovascular bundles (SNVBs) and are secured using a bioadhesive approach, without inducing fibrosis or immune activation in SNVBs. SpNWSs deliver wireless stimulation using subcutaneously implanted hydrogel thin film as battery-free powering electrodes with a capacitive-coupling effect. In a chronic inflammatory bowel disease rat model, splenic nerve stimulation by an SpNWS significantly reduced colitis severity and restored intestinal immune balance by suppressing TH1/TH17 responses and enhancing TH2/Treg activity. This work establishes a bioelectronic platform that combines material compliance, interface adaptability and wireless power delivery to enable organ-specific neuromodulation for electroceutical treatment of refractory diseases.