"Living Electrodes" May Change Neurological Device Design
Research on biohybrid approach could improve brain-computer interfaces
As a clinician, Mijail D. Serruya, MD, PhD, assistant professor in the Department of Neurology, understands the devastating effects of many neurological diseases and conditions. That awareness has driven his research interest at the Vickie and Jack Farber Institute for Neuroscience at Jefferson in brain-computer interfaces, neuroprosthetics designed to restore brain and nervous system function.
Scientists in the field have developed a few devices, such as deep-brain stimulators, that penetrate the brain with synthetic electrodes; however, overall progress has been slow because when a nonorganic device is implanted into living tissue, it is attacked by the body’s natural defense mechanisms. Moreover, the brain’s salty, warm, and wet environment destroys electronic components. “Everything you implant to the body has issues of biocompatibility and biostability,” Serruya says.
To overcome those problems, Serruya is part of a team that is going beyond the limitations of existing synthetic brain-computer interfaces. In research published recently in Advanced Functional Materials, he and co-authors from the University of Pennsylvania and Pennsylvania State University described their work using a biohybrid approach that builds on their earlier development of microtissue-engineered neural networks.
By combining living neurons, biomaterial, and microelectrode technology, they have now created “living electrodes” for implantation in the brain and direct integration with the nervous system. These biologically based microstructures could provide more stable modulation of neural activity, enable greater function, and have more permanence than conventional nonorganic devices.
Living electrodes are built from neurons, held in column-like structures resembling threads with the thickness of a human hair. Various neuron subtypes can be used, so the interfaces would be able to stimulate, inhibit, or change neural circuitry. Cells may be modified in the laboratory for particular purposes before the columns are built.
Only the biological part of the construct penetrates the brain. Optical or electrical components sit on the brain’s surface. Keeping the synthetic parts out of the brain, the researchers reason, will reduce the foreign body response caused by contact with conventional materials.
Surrounded by a hydrogel, living electrodes are microinjected to a depth in the brain chosen for a specific purpose. The architecture of the tiny threads lets them be delivered to target locations and keeps the neurons confined to where they are supposed to be.
By selecting which cells are used, patients could be treated with more targeted specificity than is possible with synthetic interfaces. For example, Serruya explains, in Parkinson’s disease, living electrodes could secrete and replace dopamine to restore movement; for epilepsy, the constructs could secrete the inhibitory neurotransmitter GABA at seizure sites. In their paper, the researchers also discussed how living electrodes might be used to treat other neurological conditions, from severe motor impairments, chronic pain, and Alzheimer’s disease to stroke, cerebral palsy, and refractory depression.
Autologous neurons, derived from the individual receiving the living electrodes, could be used in building the columns. This would eliminate the need for immune suppression and might be useful in certain types of gene therapy. Because living electrodes are tiny, much smaller than synthetic devices, dozens could be implanted at one time to modulate a whole brain network.
Living electrodes are still in early development. The researchers have created them in the laboratory and implanted them in rats. Testing has shown that the biologically based interfaces make synapses, linking neuron to neuron. Upcoming work will explore how living electrodes function and see if behavior, such as movement, can be changed or controlled via the living electrodes. That process will allow researchers to change components, define how many neurons should be in each microstructure, determine how to engineer them for safe removal if needed, and refine them further.
Serruya continues to study synthetic brain-machine interfaces as well, to find approaches that can be used with current devices. That research also helps clarify his work with the biohybrids.
“Living electrodes are a platform,” he says. “This is a starting point, not a final product.”
By Robin Warshaw