Clinical trials to repair spinal cord injuries in people are a step closer following the successful implantation of a 3D printed spinal cord into rats with severe spinal cord injury.
The rapidly 3D printed spinal cords were loaded with neural stem cells prior to being implanted in the injured rats.
The implants, described in 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.
The advance by researchers at University of California San Diego School of Medicine and Institute of Engineering in Medicine promotes renewal in axons, which are long extensions on nerve cells that reach out to connect to other cells.
“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 co-senior author Mark Tuszynski, MD, PhD, professor of neuroscience and director of the Translational Neuroscience Institute at UC San Diego School of Medicine.
“The new work puts us even closer to the real thing because the 3D scaffolding recapitulates the slender, bundled arrays of axons in the spinal cord,” said co-first author Kobi Koffler, PhD, assistant project scientist in Tuszynski’s lab. “It helps organise regenerating axons to replicate the anatomy of the pre-injured spinal cord.”
Co-senior author Shaochen Chen, PhD, professor of nanoengineering and a faculty member in the Institute of Engineering in Medicine at UC San Diego, and colleagues 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,” Chen said.
According to UC San Diego, the implants contain dozens of tiny, 200μm wide channels that guide neural stem cell and axon growth along the length of the spinal cord injury. The printing technology used by Chen’s team produces two-millimetre sized implants in 1.6 seconds.
The process is said to be scalable to human spinal cord sizes, so as a proof of concept, the researchers printed four-centimetre-sized implants modelled from MRI scans of actual human spinal cord injuries that were printed within 10 minutes.
“This shows the flexibility of our 3D printing technology,” said co-first author Wei Zhu, PhD, nanoengineering postdoctoral fellow in Chen’s group. “We can quickly print out an implant that’s just right to match the injured site of the host spinal cord regardless of the size and shape.”
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 are said to have regained significant functional motor improvement in their hind legs.
“This marks another key step toward conducting clinical trials to repair spinal cord injuries in people,” Koffler said. “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.”
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.