With the help of a 3-D printed hydrogel implant, researchers have demonstrated that they can restore leg movement in rats with severe spinal cord injuries (Nat. Med. 2019, DOI: 10.1038/s41591-018-0296-z). Using a fast, light-based printing technique, the team tailored the implants to precisely fit a cut or tear in a spinal cord, guiding nerve cells to grow across the injury site and reestablish neural connection.
About 17,700 people in the US suffer from spinal cord injuries every year. Surgery and therapy can restore some movement or sensation in affected parts of the body, but these injuries are usually permanent because damaged spinal nerves do not regenerate on their own.
Researchers have been trying to coax spinal nerves to regrow and connect through surgically grafted polymer implants. These devices can contain neural stem cells that eventually turn into neurons while also secreting molecules that stimulate the growth of the neurons already at the lesion site. The scaffolds then act like a bridge to direct the cells’ growth so that the two ends of the lesion reconnect.
The efforts are promising but progress has been slow. Part of the problem is that the cubical or tube-like scaffolds made so far are poor fits for the usually randomly shaped spinal lesions. This mismatch means the devices often fail to closely connect the two ends of a lesion. “It will be necessary to make the scaffold formfitting so it can contact the spinal cord intimately for the tissue to really integrate,” says Ann M. Parr, a neurosurgeon at the University of Minnesota, who was not involved in the new work.
A team of researchers at the University of California, San Diego, led by neuroscientists Jacob Koffler and Mark H. Tuszynski, and nanoengineer Shaochen Chen, made such a scaffold using a patented 3-D printing technique they developed. The method uses millions of microscopic mirrors to shine ultraviolet light onto a solution of photocurable polymers. Based on the pattern of the reflected light in the solution, the polymers solidify and form the desired 3-D shape. This technique produces complex structures and is much faster than conventional methods that deposit materials layer by layer.
To make the spinal implants, the researchers feed a digital model created from magnetic resonance imaging scans of a spinal cord injury into their printer, directing it to make a scaffold that matches the lesion. It takes the printer 1.6 seconds to print 2-mm-wide scaffolds for rats, whereas conventional 3-D printing takes half an hour. The scaffolds have a solid core surrounded by material with 200-µm-wide channels. The implants are made of polyethylene glycol and gelatin methacrylate. Nerve cells are picky about the materials they grow on, Chen says, but they “love to grow inside this material. They go straight inside the channels.”
To test the implants, the team split rats with severed spinal cords into three groups: one group received implants loaded with neural stem cells suspended in a cocktail of growth factor proteins, another got empty scaffolds, and the third received just stem cells. Six months later, animals with the cell-loaded implants were able to move their hind legs, while those in the other two groups could not.
Closer inspection of the rats’ spines showed that the native neurons’ axons—the thread-like parts of neurons through which they send electrical signals—grew into the microchannels, where they connected with the stem cells’ axons, which in turn connected with axons from neurons on the other side of the lesion. Axon growth was eight times greater in cell-loaded scaffolds compared with empty ones. And in rats that just got cell grafts, axons grew in all directions and did not always connect to those on the other end. The researchers are now testing the implants in monkeys, which more closely represent lesions seen in humans.
Michael C. McAlpine, a mechanical engineer at the University of Minnesota, calls this excellent work and something that could be used with other implant designs. He and Parr are also working on 3-D printed implants for spinal cord injury. They print cells directly into their scaffolds, which allows them to place various types of cells exactly where they are needed for growth in an implant. The UC San Diego team is “focusing on anatomical accuracy,” he says. “In the future maybe the two approaches could be combined for even better results.”