Spinal cord injuries or disease are often devastating, leading to significant impairment, pain, and paralysis. While rehabilitation shortly after injury may restore some patients’ mobility, and neuromodulation can temporarily restore electrical impulses, the spinal cord itself is no longer functional when nerves are damaged or severed. A biomaterial hydrogel developed out of a multi-institutional consortium, called Mend the Gap, holds the potential to create an environment to regrow nerves.
In spinal injury or tissue damage that occurs following a disease affecting the spine, there is a gap in the spine that interrupts nerve signals. As a result of the collaboration, a biomaterial has been devised that could close that gap and allow for nerves to reconnect. The soft gel, which is currently moving into preclinical research, contains miniature magnetic rods that can be aligned in a particular direction with a magnet. The rods would then create guides for nerves to grow along.
Anisotropic Hydrogel Promising for SCI
Prof. Laura De Laporte, PhD, a chemical engineer in advanced materials for biomedicine at the DWI – Leibniz Institute for Interactive Materials, of Aachen, Germany, began developing the soft gel, referred to as an anisotropic gel, in an effort toward eventual improvement in spinal cord lesion treatment. De Laporte’s work is being studied within the Mend the Gap consortium.
“The whole idea was to have a material that you can inject, so it’s minimally invasive but it also aligns,” said De Laporte, explaining that implants or scaffolds require removing tissue to accommodate the device, which can lead to even more damage to spinal nerves. “I wanted something you could inject as a liquid and then it aligns after you inject and stays aligned, and the nerves would have highways basically to be guided across the injury site.”
A liquid gel that provides structure is particularly useful for spinal cord treatment as lesions vary from patient to patient. “Each patient is different, and a liquid [hydrogel] can adjust to an irregular shape and then it is solid,” said De Laporte. “Over time material is replaced by tissue,” she said. “The microgels can disappear because the ideal is that the biology takes over and creates an aligned natural scaffold.”
The patented anisotropic gel, initially developed through European grant funding awarded to De Laporte, combines two components: a crosslinked macromolecule hydrogel and pre-crosslinked micron hydrogel. Within the micron hydrogel, small rod-shaped cylinders (2-5 micrometer diameter x 20-50 micrometer length) infused with iron oxide nanoparticles, allow for a magnetically oriented design, explained De Laporte. When the micron hydrogel is added to water and a small magnet is applied, the rods can be aligned in a desired direction. Subsequently, the macro hydrogel is injected, surrounds the rods, and is crosslinked to affix the rods in place, she said. The biomaterial gels absorb over time as nerves and tissue grow in its place.
Liquid to Fill SCI Injury Spaces
A medical team member of the Mend the Gap collaboration, Wolfram Tetzlaff, MD, PhD, professor of surgery and zoology at the University of British Columbia in Vancouver, sees the anisotropic hydrogel as a feasible method to treat spinal cord injury. “The way the gel is envisioned, it would mold itself to the shape of the lesion," said Tetzlaff. “The lesion itself might need some treatment because the edge of a spinal cord lesion often undergoes some scarring so there will be the need for drug delivery and additional treatments that modify the scar and also stimulate the growth of the axon.” A gel medical device, should the technology prove effective in further study, would likely be developed in combination with a pharmaceutical to stimulate nerve cell growth.
Several practical questions have yet to be determined such as whether the most appropriate use is in acute or chronic injury and the injection process. The cavity in the spinal column is small, often visually obstructed, and injury may be in multiple locations, explained Tetzlaff, adding that a visually guided robot that can accommodate for spinal movement when breathing is being developed. “Spinal cord injuries have so many flavors and shapes and types, and they undergo changes over time,” he said. Initial in vivo testing will include 3D-printed mock spinal cords, Tetzlaff shared.
Translating Prospect to Next Steps
While still early in the development process, researchers are cautiously optimistic about the prospect of the anisotropic biomaterial gel. “We don’t want to cause any false hope for spinal cord injury patients,” said De Laporte. “It is a new type of material and I believe it is promising, but we only show proof of principle in vitro [at this point].”
That’s where researchers from Mend the Gap come in: teams are currently preparing to begin in vivo studies of the biomaterial gel. Mend the Gap currently brings together 32 members from around the world, including engineers, surgeons, and researchers, each with their own aspect of spinal cord injury expertise. Participants hail from Australia, Canada, Europe, and the United States, and in 2020 were supported with $24 million from the New Frontiers in Research Fund of Canada. Bringing together a multidisciplinary group of top talent from various specialties is the “only way to move ahead on spinal cord injuries, explained Tetzlaff, due to the complexity of lesions.