Bidirectional Brain-Machine Communication and Neuromodulation by Supramolecular Hydrogel Neural Probes for Chronic Pain Management.

Chronic pain continues to pose a significant therapeutic challenge due to its complex pathophysiology and the limited efficacy of conventional pharmacological treatments. Brain-machine interfaces (BMIs) have emerged as a promising strategy for recording neural activity, modulating neural circuits, and treating neurological disorders. However, the long-term performance of conventional rigid implantable probes is severely constrained by their mechanical mismatch with soft brain tissue. This mismatch provokes chronic inflammatory responses and results in gradual signal deterioration. Additionally, most existing probes lack integrated functionality for simultaneous in situ neuromodulation and neural signal recording. In this work, we developed a supramolecular hydrogel based on α-helical polypeptide cross-linkers, achieving an optimal balance of mechanical compliance, electrical conductivity, and optical transparency. When implanted in the rat prelimbic cortex, the hydrogel probe enabled stable recording of local field potentials (LFPs) for up to 16 weeks. Importantly, the probe enabled in situ neuromodulation while concurrently recording evoked LFPs, resulting in enhanced prelimbic cortical activity, increased mechanical withdrawal thresholds, and reduced cold allodynia in a chronic neuropathic pain model. These findings advance neural interface technology by enabling integrated, long-term monitoring and neuromodulation, representing a paradigm shift in the design of implantable devices for chronic pain therapy.