For the first time, researchers have used rapid 3D printing technologies to create a spinal cord, then successfully implanted that scaffolding, loaded with neural stem cells, into sites of severe spinal cord injury in rats.

The implants, described in a study published in the journal of Nature Medicine, are intended to promote nerve growth across spinal cord injuries, restoring connections and lost function. In rat models, the scaffolds supported tissue regrowth, stem cell survival and expansion of neural stem cell axons out of the scaffolding and into the host spinal cord.

"In recent years and papers, we've progressively moved closer to the goal of abundant, long-distance regeneration of injured axons in spinal cord injury, which is fundamental to any true restoration of physical function," said the co-senior author. Axons are the long, threadlike extensions on nerve cells that reach out to connect to other cells.

"The new work puts us even closer to real thing," added co-first author, "because the 3D scaffolding recapitulates the slender, bundled arrays of axons in the spinal cord. It helps organize regenerating axons to replicate the anatomy of the pre-injured spinal cord."

Researchers used rapid 3D printing technology to create a scaffold that mimics central nervous system structures. "Like a bridge, it aligns regenerating axons from one end of the spinal cord injury to the other. Axons by themselves can diffuse and regrow in any direction, but the scaffold keeps axons in order, guiding them to grow in the right direction to complete the spinal cord connection," the pther co-senior author said.

The implants contain dozens of tiny, 200-micrometer-wide channels (twice the width of a human hair) that guide neural stem cell and axon growth along the length of the spinal cord injury. The printing technology used by the team produces two-millimeter-sized implants in 1.6 seconds. Traditional nozzle printers take several hours to produce much simpler structures.

The process is scalable to human spinal cord sizes. As proof of concept, researchers printed four-centimeter-sized implants modeled from MRI scans of actual human spinal cord injuries. These were printed within 10 minutes.

Researchers grafted the two-millimeter implants, loaded with neural stem cells, into sites of severe spinal cord injury in rats. After a few months, new spinal cord tissue had regrown completely across the injury and connected the severed ends of the host spinal cord. Treated rats regained significant functional motor improvement in their hind legs.

Additionally, the circulatory systems of the treated rats had penetrated inside the implants to form functioning networks of blood vessels, which helped the neural stem cells survive.

The scientists are currently scaling up the technology and testing on larger animal models in preparation for potential human testing. Next steps also include incorporation of proteins within the spinal cord scaffolds that further stimulate stem cell survival and axon outgrowth.

https://ucsdnews.ucsd.edu/feature/3d-printed-implants-show-promise-for-treating-spinal-cord-injury

https://www.nature.com/articles/s41591-018-0296-z