Images of the electrode’s degradation over four weeks at 37 °C. Inset: bright field microscopic images of the electrode tip.
Imagine a one-and-done treatment for stroke using the regenerative capacity of your brain. Tianhao Chen, Dr. Cindi Morshead’s lab, and Dr. Hani E. Naguib’s lab have developed a biodegradable electrode that can electrically stimulate neural precursor cells (NPCs).
This procedure is effective because neurons are electrosensitive cells that can respond to electrical signals. Neurons’ electrosensitivity is the underlying reason why deep brain stimulation (DBS) is currently one of the most widely used FDA-approved treatments for Parkinson’s disease, since 2002.
In DBS, electrodes are surgically implanted into the brain. The electrical stimulation from the electrodes interrupts problematic electrical signals from targeted areas in the brain. For a chronic progressive condition such as Parkinson’s disease, the electrodes are left in the patient’s brain for life.
During an interview, Dr. Cindi Morshead told me that “People use electrical stimulation all the time. This is really a repurposing of deep brain stimulation in a way.” For non-chronic brain injuries such as those caused by stroke, electrical stimulation wouldn’t need to be done on a constant, ongoing basis. The team’s electrode has been shown to degrade within days to weeks following implantation.
Although removing implanted electrodes is possible following treatment, this carries additional operative risks, including damage to brain tissue. What is novel about the Morshead’s team’s electrode is that it stimulates endogenous precursors and promotes repair, “and it wouldn’t have to be in the brain forever,” Dr. Morshead emphasized.
These biodegradable electrodes are made with the polymer poly(lactic-co-glycolic) acid (PLGA), which is used both as the substrate and insulating layer, molybdenum (Mo), and conductive polymer PEDOT:PSS. All these components are durable, yet they can degrade into safe compounds in the body over time.
Biocompatibility means that the degrading products won’t have detrimental effects on cell survival or exacerbate neuroinflammation. PGLA has been well established to be biocompatible, and Dr. Morshead’s team has confirmed that the element Mo has no detrimental effect on NPC survival.
However, neuroinflammation can occur after the application of electrical stimulation, regardless of what the electrode is made of. Therefore, they compared the inflammatory responses between their biodegradable Mo electrodes and commonly used FDA-approved Au (gold) electrodes by evaluating the number of neuroinflammatory cells (microglia and reactive astrocytes) between the two groups.
They found that there was no difference in the number of microglia and reactive astrocytes between the two groups. However, the Mo electrode outperformed the Au electrode in maintaining the survival of the resident neurons (the neurons that existed in the brain before stimulation). The resident neurons were protected by the applied electric field with the Mo electrodes for as long as eight weeks post-implantation.
Dr. Morshead explained that one possible reason for this was that although the total number of microglia was the same between the two groups, the inflammatory state of the microglia can differ, and this could be what is dictating better or worse survival.
This, along with the fact that these electrodes biodegrade into safe compounds in the brain, means the team’s Mo-coated electrodes may provide a safer and more efficient tool to deliver DBS than electrodes typically used clinically today.
Expansion of the stem cell pool
Endogenous neural stem cells (in the subventricular zone of our brain) can proliferate, self-renew, and differentiate into mature neural cells. In a foundational study, it was shown that injury will cause NPCs in the subventricular zone to divide, increase, and migrate to the site of injury. However, only a small fraction of NPCs respond this way, and injury-induced NPC activation alone is insufficient for neural regeneration and functional recovery.
To harness the power of endogenous stem cells, the Morshead group demonstrated that they could direct and facilitate neural stem cell migration using electric fields. When it comes to injured brain tissue caused by a condition such as stroke, this migratory behaviour could be beneficial if stem cell migration to the site of injury is enhanced.
Their latest research showed that electrical stimulation from the biodegradable electrodes expands the neural stem cell pool about 3-fold beyond what injury does on its own. And with electrical stimulation, more of these cells will migrate to the site of injury. Dr. Morshead explained that these stimulated neural stem cells can generate mature neurons (or neurogenesis), which can contribute to repair.
Recent work in the lab has also shown that electrical stimulation can direct neural stem cells to differentiate into oligodendrocytes. Oligodendrocytes are important for producing myelin, a component of the myelin sheath that wraps around axons. The myelin sheath is necessary for electrical conduction, communication between neurons, and brain functioning. Intentionally inducing some of the migratory neural stem cells to turn into oligodendrocytes would enhance the function of newly born neurons that come from electrical stimulation and promote full recovery of stroke-induced injury. This is currently being studied by the Morshead lab and results are not yet published.
A drug delivery system
The team is also working toward a new component to be added to the biodegradable electrode. It’s a device that would deliver drugs or viruses (the viruses would deliver gene therapy) while delivering the electrical stimulation. They call it a multimodal electrode. “So in that case, we will be able to not only activate the stem cells, get them to migrate towards the lesion site, and help with repair, but we would also be able to deliver drugs and other molecules that might enhance the damaged brain’s plasticity, or encourage the NPCs that do get to the lesion site to turn into specific cell types.”
Another step for the team is answering certain questions regarding the best stimulation paradigms for certain conditions, such as: “How long should you wait after a condition like stroke to apply direct electrical stimulation into the brain?” And, “Should we transplant the electrodes soon after the stroke, when there is still a hostile environment or do we wait?”
Stem cell transplantation has proven to be promising. However, endogenous repair, where you use cells that are resident in the brain, allows you to avoid some of the challenges faced by scientists who are involved with cell transplantation. Some of these include finding an appropriate cell source for transplantation and optimizing the integration of the new transplanted cells.
This biodegradable electrode, which never has to be removed, delivers electrical stimulation combined with drug delivery and is a very targeted approach to augment the NPCs’ capacity to achieve the following: expand their stem cell pool; undergo directed migration to the site of injury; and differentiate into functional neural cells to enhance the regenerative potential of the brain beyond what can be achieved under homeostatic conditions or conditions involving injury-induced NPC activation.
For a patient who has just suffered from a stroke, knowing that they could receive an all-in-one treatment to enhance self-repair of their injured brain could put their mind at ease.
Krystal Jacques
Latest posts by Krystal Jacques (see all)
- Biodegradable electrodes stimulate neural precursor cells to expand and migrate - May 29, 2025
- The first pancreatic organoid with all pancreatic cell types - April 3, 2025
- Freeze-thawing neural stem cells - February 19, 2025
Comments