Injectable hydrogel bioelectrostimulator for wireless deep brain neuromodulation

Abstract

Abstract Deep brain stimulation (DBS) is effective for treating neurological and psychiatric disorders. However, its tethered configuration, invasiveness, and limited tissue compatibility motivate wireless, minimally invasive alternatives. Here, we develop an in situ-gelled injectable conductive hydrogel (ICH), enabling wireless neuromodulation via electric-field localization under volume conduction. The ICH forms in vivo through bio-catalyzed polymerization and electrostatic self-assembly, yielding a stable, highly conductive, tissue-soft, and biocompatible network. Under high-frequency capacitive coupling, impedance difference between the ICH and surrounding brain tissue induces interfacial polarization and charge accumulation, locally concentrating the electric field to activate nearby neurons. This mechanism is supported by enhanced calcium signaling, increased c-Fos expression, and electrophysiological evidence of balanced basal ganglia-cortical activity. In a Parkinson’s disease rat model, ICH-mediated stimulation improved locomotor behavior, preserved dopaminergic neurons, and restored functional connectivity and structural integrity as revealed by fMRI. This injectable hydrogel bioelectronics provides a platform for minimally invasive, wireless neuromodulation therapies.