Researchers at the University of California in San Diego School of Medicine and Institute of Engineering in Medicine have used rapid 3D printing technologies to create a spinal cord.
It was then successfully implanted and loaded with neural stem cells into sites of severe spinal injuries in rats.
The implants are intended to promote nerve growth across spinal growth injuries, restoring connections and lost function. In rats, they supported tissue regrowth, stem cell survival and expansion of neural stem cell axons.
Mark Tuszynski, professor of neuroscience and director of the Translation Neuroscience Institute at UC San Diego School of Medicine, said: “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.”
3D printing technology was used to create a scaffold that mimics central nervous system structures – with the process scalable to human spinal cord sizes. The team used photocrosslinkable biocompatible materials gelatin methacrylate (GelMA) and poly(ethylene glycol) diacrylate (PEGDA). GelMA is modified from denatured collagen and retains natural cell-binding motifs needed to support cellular adhesion, proliferation, and migration. PEGDA has been approved by the Food and Drug Administration (FDA) for use in humans and is a well-known non-immunogenic biocompatible material.
Professor Shaochen Chen, professor of nanoengineering, said: “The biomimetic hydrogel scaffolds can be designed to be biodegradable, i.e. once the spinal cord injury is repaired, the scaffold will be slowly degraded and disappeared, eliminating the need to remove the foreign implant after recovery.
“Neural stem cells were loaded into the micro-channels in the scaffold after 3D printing and right before the implantation into the animals. We used neural stem cells taken from embryonic day 14 spinal cords of rats.”
Researchers grafted the two-millimetre 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.
Kobi Koffler, assistant project scientist in Tuszynski’s lab, said: “This marks another key step toward conducting clinical trials to repair spinal cord injuries in people. The scaffolding provides a stable, physical structure that supports consistent engraftment and survival of neural stem cells. It seems to shield grafted stem cells from the often toxic, inflammatory environment of a spinal cord injury and helps guide axons through the lesion site completely.”
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.
Wei Zhu, nanoengineering postdoctoral fellow in Professor Chen’s group, said: “Vascularisation is one of the main obstacles in engineering tissue implants that can last in the body for a long time. 3D printed tissues need vasculature to get enough nutrition and discharge waste. Our group has done work on 3D printed blood vessel networks before, but we didn’t include it in this work. Biology just naturally takes care of it for us due to the excellent biocompatibility of our 3D scaffolds.”
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.
