Where some parts of the human body are able to heal relatively well following an injury, a damaged spinal cord is one that has a notoriously difficult time. But a new type of artificial scaffold is providing scientists with new cause for optimism. It features a novel design that encourages regenerating neurons to grow towards one another and bridge busted connections more efficiently, offering new hope for improved treatments.
When a spinal cord becomes injured, it can sever important connections between the brain and body and impede the victim's ability to move and feel sensations, and can even lead to paralysis. Unlike some other nerves, such as those in the fingers and legs, that can heal themselves without too much trouble, those in the central nervous system, the brain and spinal cord, work a little differently.
“Currently, regenerating injured neurons in the spinal cord is a real challenge,” says Professor Marco Terenzio, from Japan's Okinawa Institute of Science and Technology (OIST). “Only a few types of neurons in the spine have a limited ability to heal. And on top of that, the neurons may need to grow up to several millimeters, and there may be scar tissue in the way. So, we need to provide an artificial scaffold to give the neurons a helping hand and bridge the gap.”
We have seen some interesting examples of these types of scaffolds designed to treat spinal cord injuries. One from 2018 consisted of a silicon scaffold covered in 3D-printed stem cells that could be implanted into the site of the injury to generate new connections between the remaining nerves. Another from earlier this year incorporated gene therapy to promote the regeneration of nerve fibers and improve tissue repair in mice.
The OIST scientists sought to break new ground in this area by focusing on the way neurons grow. Normally, they develop from the center outwards in a radial fashion, but in circumstances where a connection with a neighboring neuron needs repairing, having them grow in a straight line to bridge the gap is more desirable.
So the researchers formed a scaffold to promote this type of behavior that mimicked the extracellular matrix, which is the fibrous material that offers structural and chemical support for neurons to grow. This involved designing scaffolds with grooves and indentations designed to encourage directional (rather than radial) growth of the neurons, and using an advanced printing technology to create the finished product.
This is known as 2-photon lithography, and uses a light-sensitive polymer that is blasted with a laser, causing it to harden in response. But firing the laser only at desired sections of the material leaves sections that are non-hardened and can be easily washed away, leaving behind the carefully designed scaffold as a result.
“It works a bit like 3D printing, but in reverse,” says Terenzio. “Instead of building up by depositing material where it’s needed, the structure is created by removing material.”
This structure proved to be thermally and mechanically stable, as well as biocompatible, with the scientists successfully using it to grow types of mouse neurons responsible for relaying sensation to the brain and for muscle movement. These neurons were able to attach and grow over the scaffold as desired, and when used on a porous version, actually grew into the structure as well as over the top.
“We found that the neurons were able to penetrate all the layers of the scaffold, which was very exciting to see,” says Terenzio. “The next goal is to use this design as a template for developing future scaffolds that could be used for in vivo experiment in mice.”
Part of that work will involve experimenting with different types of materials and fine-tuning the design, exploring how it could be used to treat other types of injuries. Another challenge will be reducing the cost of the production process, which is currently described as "prohibitively expensive" and takes days to print scaffolds of a large enough size.
“The technology is still very much in its infancy, but we are hopefully that it will improve in cost and efficiency over time,” says. Terenzio. “We were very fortunate to be able to gain access to this machine through the nanofabrication and mechanical engineering services of the OIST Engineering Section.”
The research was published in the journal Materials Science and Engineering: C, while the video below shows the regenerating neurons visualized with a confocal microscope.
