When neurons (nerve cells) are damaged by degenerative disease or injury, they have little if any ability to heal on their own. Restoring neural networks and their normal function is therefore a significant challenge in the field of tissue engineering.
These fundamental units of the brain and nervous system – composed of the cell body, the dendrites and the axon (a long, thin extension responsible for communicating with other cells) – receive sensory input from the external world, send motor commands to our muscles and for transform and relay the electrical signals at every step in between.
“Our novel method of creating ‘mini-brains’ opens the door to finding solutions for various neurological impairments"Prof. Shefi and Reut Plen
How "mini-brains" help repair nerve cells
Prof. Orit Shefi and doctoral student Reut Plen from the Kofkin Faculty of Engineering at Bar-Ilan University (BIU) have developed a novel technique to overcome this challenge using nanotechnology and magnetic manipulations – one of the most innovative approaches to creating neural networks. Their research was recently published in the peer-reviewed journal Advanced Functional Materials under the title “Bioengineering 3D Neural Networks Using Magnetic Manipulations.”
The US Food and Drug Administration (FDA) has already approved the use of magnetic nanoparticles for diagnostic and imaging purposes and in cases of severe injury. The steps taken by the BIU research group will advance the technology for future clinical use.
“This is only the beginning,” Shefi and Plen said. “Our novel method of creating ‘mini-brains’ opens the door to finding solutions for various neurological impairments which will hopefully improve the quality of life of numerous patients.”
To create neural networks, the researchers injected magnetic iron oxide nanoparticles into neural progenitor cells, turning them into independent magnetic units. They then exposed the progenitor cells that develop into neurons to a number of pre-adjusted magnetic fields and remotely directed their movement within a three-dimensional and multilayered collagen substrate that mimics the natural characteristics of body tissue. Through these magnetic manipulations, they created three-dimensional “mini-brains” – functional and multilayered neural networks that mimic elements found in the brains of mammals.
A non-invasive method
After the collagen solution solidified into a gel, the cells remained in place according to the remotely applied magnetic fields. Within a few days, they developed into mature nerve cells, formed extensions and connections, showed electrical activity and thrived in the collagen gel for at least three weeks.
“This method paves the way for the creation of 3D cell architecture on a customized scale for use in bioengineering, therapeutic and research applications, both inside and outside the body,” Plen said. “Since the 3D neural networks we created simulate innate properties of human brain tissues, they can be used as experimental ‘mini-brains’ and as a model for the study of medicinal drugs, for investigating communication between tissues and as a way to build artificial networks for interfaces between engineering and biological components.
"The advantage of using this method is that magnetic fields can affect cells located deep inside the body in a non-invasive manner"Reut Plen
Is it safe?
“In addition, the model suggests an interesting prospect for injecting such a gel containing cells in its liquid state, introducing it into the nervous system and organizing the cells into the correct structure with the assistance of magnetic forces," she said. "The advantage of using this method is that magnetic fields can affect cells located deep inside the body in a noninvasive manner.”
Inserting magnetic particles into cells, and into nerve cells in particular, raises questions regarding the safety of future medical applications.
“The issue of safety is important, and we’ve devoted much thought and research into it,” Shefi concluded. “In the first step, we tested the effect of different particles on cell health in culture. In addition, we coated the magnetic particles with a biocompatible protein. The coating creates a buffer between the magnetic element and the cell and encourages penetration of the nanoparticles.
“Importantly, iron – the building block of the nanoparticle – exists naturally in the body, so it isn’t a foreign substance," she said. "Additionally, the same gel with magnetic particles has been tested in our laboratory and found safe to use in animal models.”