Cryogel-based neurostimulation electrodes to activate endogenous neural precursor cells

The delivery of electrical pulses to the brain via penetrating electrodes, known as brain stimulation, has been recognized as an effective clinical approach for treating neurological disorders. Resident brain neural precursor cells (NPCs) are electrosensitive cells that respond to electrical stimulation by expanding in number, migrating and differentiating which are important characteristics that support neural repair. Here, we report the design of a conductive cryogel brain stimulation electrode specifically developed for NPC activation. The cryogel electrode has a modulus switching mechanism permitting facile penetration and reducing the mechanical mismatch between brain tissue and the penetrating electrode. The cryogel demonstrated good in vivo biocompatibility and reduced the interfacial impedance to deliver the stimulating electric field with lower voltage under charge-balanced current controlled stimulation. An ex vivo assay reveals that electrical stimulation using the cryogel electrodes results in significant expansion in the size of NPC pool. Hence, the cryogel electrodes have the potential to be used for NPC activation to support endogenous neural repair. STATEMENT OF SIGNIFICANCE: The objective of this study is to develop a cryogel-based stimulation electrode as an alternative to traditional electrode materials to be used in regenerative medicine applications for enhancing neural regeneration in brain. The electrode offers benefits such as adaptive modulus for implantation, high charge storage and injection capacities, and modulus matching with brain tissue, allowing for stable delivery of electric field for long-term neuromodulation. The electrochemical properties of cryogel electrodes were characterized in living tissue with an ex vivo set-up, providing a deeper understanding of stimulation capacity in brain environments. The cryogel electrode is biocompatible and enables low voltage, current-controlled stimulation for effective activation of endogenous neural precursor cells, revealing their potential utility in neural stem cell-mediated brain repair.