Cryogel-based neurostimulation electrodes to activate endogenous neural precursor cells

Tianhao Chen; Kylie Sin Ki Lau; Sung Hwa Hong; Hao Tian Harvey Shi; Stephanie N Iwasa; Jia Xi Mary Chen; Terek Li; Taylor Morrison; Suneil K Kalia; Milos R Popovic; Cindi M Morshead; Hani E Naguib

doi:10.1016/j.actbio.2023.08.056

Cryogel-based neurostimulation electrodes to activate endogenous neural precursor cells

Acta Biomater. 2023 Nov:171:392-405. doi: 10.1016/j.actbio.2023.08.056. Epub 2023 Sep 7.

Authors

Affiliations

¹ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
² Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
³ Department of Mechanical and Materials Engineering, Western University, London, Ontario, Canada.
⁴ The KITE Research Institute, Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada; CRANIA, University Health Network and University of Toronto, Toronto, Ontario, Canada.
⁵ Department of Materials Science and Engineering, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada.
⁷ The KITE Research Institute, Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada; CRANIA, University Health Network and University of Toronto, Toronto, Ontario, Canada; Department of Neurosurgery, University Health Network, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
⁸ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; The KITE Research Institute, Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada; CRANIA, University Health Network and University of Toronto, Toronto, Ontario, Canada.
⁹ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; The KITE Research Institute, Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada; CRANIA, University Health Network and University of Toronto, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address: cindi.morshead@utoronto.ca.
¹⁰ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada; Department of Materials Science and Engineering, University of Toronto, Toronto, Ontario, Canada; Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada. Electronic address: naguib@mie.utoronto.ca.

PMID: 37683963
DOI: 10.1016/j.actbio.2023.08.056

Abstract

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.

Keywords: Brain stimulation; Conductive polymers; Cryogel; Neural precursor cells; Neuromodulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cryogels*
Electric Conductivity
Electric Stimulation
Electrodes
Electrodes, Implanted
Neural Stem Cells*
Neurons / physiology

Substances

Cryogels

Grants and funding

CIHR/Canada