
This study demonstrates cellular repair in areas of brain injury using biodegradable electrical stimulation electrodes. Electrical stimulation triggers the proliferation and migration of neural stem cells, which repair the injury. These devices could be the key to future therapies that help repair the brain safely and effectively, reducing the need for additional invasive procedures.
Neurological disorders such as stroke, Alzheimer’s disease, and other conditions that affect the nervous system are a leading cause of long-term disability worldwide.
Unfortunately, there are currently no effective treatments to replace the brain cells that are lost due to these diseases or injuries. Therefore, there is an urgent need to develop new therapies that can promote brain repair and help patients recover.
One promising approach involves the use of endogenous neural stem cells and progenitor cells, which together are called neural precursor cells (NPCs).

These cells are found in small numbers in a specific area of the brain called the subventricular zone (SVZ), which lines the lateral ventricles. Under normal conditions, these cells are involved in the creation of new neurons, contributing to the ongoing process of neurogenesis (formation of new neurons) throughout life.
When the brain is injured, these cells are activated, resulting in increased production of new cells and their migration to injured areas. However, this natural activation is usually not enough to fully repair the brain or restore its functions.
Research shows that when we combine this natural activation with the administration of certain drugs or small molecules, there is a significant improvement in the capacity for neural repair and brain functions.
In addition, recent studies have found that NPCs respond to electrical stimulation, which offers a new way to activate them more effectively.
Initially, experiments showed that when exposed to an electric field in the laboratory, NPCs rapidly migrated toward the negative side of the field.

Subsequent animal studies have shown that applying electrical stimulation to the brain not only increases the proliferation of these cells, but also promotes the formation of new neurons and cells that form the myelin sheath (oligodendrocytes), which are essential for proper nerve function.
In addition, electrical stimulation has been associated with increased formation of new blood vessels, which improves the delivery of oxygen and nutrients to the injured brain.
A specific electrical stimulation technique, called transcranial direct current electrical field stimulation (tDCS), has been shown to be effective in eliciting responses from NPCs, inducing the migration and formation of new neurons in the subventricular zone.
However, tDCS faces challenges, such as the difficulty in precisely controlling the direction of the applied electrical fields, which may limit its effectiveness. In addition, prolonged use of direct current can cause damage to brain tissue, such as the generation of reactive oxygen species (ROS), which are molecules that are harmful to cells.

Transcranial direct current stimulation (tDCS) is a non-invasive, painless brain stimulation treatment that uses direct electrical currents to stimulate specific parts of the brain. Source: Montreal Neurotherapy Center
To overcome these limitations, a new approach has been developed using biphasic monopolar intracranial stimulation (BPMP) electrodes. These electrodes deliver electrical stimulation in a balanced manner, reducing the risk of damage to brain tissue and the electrodes.
Traditional platinum electrodes, while effective, have problems such as stiffness, which can cause brain damage. As a result, alternatives made from softer materials, such as cryogels, have emerged, which offer gentler stimulation with a lower risk of inflammation.
Another innovation is the development of biodegradable electrodes, which degrade naturally after use, eliminating the need for surgical removal.
These electrodes are made from materials such as poly(lactic-co-glycolic acid) (PLGA), molybdenum (Mo) and conductive polymers, and are designed to provide effective stimulation for a specific period of time before being absorbed by the body.
In this study, researchers from the University of Toronto, Canada, designed and tested an implantable biodegradable electrode for brain stimulation.

Design and fabrication of biodegradable electrode for brain stimulation. a) Design of biodegradable electrodes. The dimensions of each of the cortical penetration probes are 2 mm long and 300 μm wide in the cortex. The width of the molybdenum probe is 150 μm. b, c) Brightfield and magnified image (c) of the stimulation electrode. The uninsulated stimulation site is 350 μm by 1000 μm. d, e) Optical images to demonstrate the flexibility of the electrode array (d) and probe implants after laser cutting (e). f) Setup for brain stimulation with current-controlled balanced-charge biphasic monopolar stimulation. The optimized waveform for activation of NPCs is delivered through the stimulator. The data acquisition (DAQ) unit is connected to record the voltage. g) Schematic of coronal hemisection showing the placement of biodegradable electrodes in the cortex of the mouse brain. During stimulation, neural precursor cells (NPCs) in the subventricular zone lining the walls of the lateral ventricle (LV) proliferate and migrate toward the cathode (−) in response to the applied electric field (EF). +: anode.
The device was manufactured with materials such as PLGA, molybdenum and the conductive polymer PEDOT:PSS, ensuring biocompatibility and efficacy in activating neural precursor cells for up to seven days after implantation.
This was sufficient to observe a significant expansion in the number of endogenous neural precursor cells, indicating that the electrode promoted the cell proliferation necessary for neural repair.

Biocompatibility. a-b) Photomicrographs of implantation sites of biodegradable Au and MoPH3 electrodes (dotted lines) in coronal brain sections stained with Iba1+ (green), GFAP+ (red) (a) and NeuN+ (cyan) cells (b) 8 weeks after implantation, Dapi (blue) labels all cell types and NeuN (cyan) labels only mature neurons, both showing an increase in the region injured and stimulated by the biodegradable MoPH3 electrode when compared to the Au control. Indicating greater cellular repair in this region.
In summary, advances in the design of biodegradable electrodes for brain stimulation offer a promising new strategy for the treatment of neurological disorders, by promoting the activation of NPCs and, potentially, the regeneration of damaged brain tissue.
These devices may hold the key to future therapies that help repair the brain safely and effectively, reducing the need for additional invasive procedures.
READ MORE:
Biodegradable stimulating electrodes for resident neural stem cell activation in vivo
Tianhao Chen, Kylie Sin Ki Lau, Aryan Singh, Yi Xin Zhang, Sara Mohseni Taromsari, Meysam Salari, Hani E. Naguib, and Cindi M. Morshead
Biomaterials, Volume 315, April 2025, 122957
Abstract:
Brain stimulation has been recognized as a clinically effective strategy for treating neurological disorders. Endogenous brain neural precursor cells (NPCs) have been shown to be electrosensitive cells that respond to electrical stimulation by expanding in number, undergoing directed cathodal migration, and differentiating into neural phenotypes in vivo, supporting the application of electrical stimulation to promote neural repair. In this study, we present the design of a flexible and biodegradable brain stimulation electrode for temporally regulated neuromodulation of NPCs. Leveraging the cathodally skewed electrochemical window of molybdenum and the volumetric charge transfer properties of conductive polymer, we engineered the electrodes with high charge injection capacity for the delivery of biphasic monopolar stimulation. We demonstrate that the electrodes are biocompatible and can deliver an electric field sufficient for NPC activation for 7 days post implantation before undergoing resorption in physiological conditions, thereby eliminating the need for surgical extraction. The biodegradable electrode demonstrated its potential to be used for NPC-based neural repair strategies.
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