An Ionotropic Alginate-Gelatin Hydrogel for Expanded Deep Brain Stimulation in Epilepsy Treatment

Deep brain stimulation (DBS) has shown remarkable clinical success in treating Parkinson’s disease and epilepsy, yet patient-specific, multi-target programming remains elusive. Current wired, multi-contact percutaneous systems carry risks of infection, restricted mobility, and surgical complications from multiple intracranial implants. Here, we present a robust DBS strategy based on the Ionotropic Alginate-Gelatin Hydrogel (IAGH) specifically designed to conformally interface with neural tissue and overcome current DBS limitations. IAGH enables the targeting of deep brain regions with limited invasion. IAGH conformally integrates with brain tissue, improving the electrode-tissue interface and potentially broadening the effective stimulation region. Meanwhile, IAGH exhibits a resistivity of 7.556 kΩ×cm which is comparable to that of conventional ionically conductive hydrogels and enables effective electrical interfacing with neural tissue. Additionally, IAGH enables frequency-dependent control of calcium ion release under electrical stimulation, amplifying calcium transients in targeted brain regions by up to 9-fold. This enhancement markedly increases the probability of presynaptic vesicle release, thereby improving the therapeutic efficacy of neuromodulation and simultaneously enabling clearer signal acquisition during stimulation efficacy. In epileptic rats, IAGH treatment led to marked symptom suppression and reduced hippocampal damage. In porcine models, IAGH significantly enhanced the amplitude and energy of deep brain signals, highlighting its superior conductivity and signal capture performance. These findings demonstrate IAGH’s bidirectional conductance and establish its potential for real-time monitoring of pathological brain states. • An injectable ionotropic alginate–gelatin hydrogel (IAGH) is developed as a tissue-conformal interface to expand Deep Brain Stimulation (DBS) stimulation coverage. • IAGH provides low-impedance ionic conduction and supports reliable in vivo LFP recording. • Electrical stimulation triggers frequency-dependent Ca²⁺ release, leading to an 9-fold increase in local calcium transients and enhanced synaptic activity. • In epileptic rats, IAGH-assisted DBS suppresses seizures and mitigates hippocampal damage versus conventional DBS. • In pigs, IAGH expands the spatial coverage for deep-brain signal acquisition and enables acquisition of higher-energy signals, supporting scalable neuromodulation and monitoring.