Paralyzed rats walk again after scientists 3D-print a new spinal cord
People who have suffered crippling spinal injuries have been offered fresh hope of walking again by scientists using state of the art 3D technology.
For the first time, researchers have used rapid 3D printing technologies to create a spinal cord, before successfully implanted the scaffolding, loaded with neural stem cells, into sites of severe spinal cord injury in rats.
The implants are intended to promote nerve growth across spinal cord injuries, restoring connections and lost function.
In rats, 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 team at UC San Diego used rapid 3D printing technology to create a scaffold that mimics central nervous system structures
Study co-senior author Professor Mark Tuszynski, of the University of California San Diego, 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.’
Axons are the long, thread-like extensions on nerve cells that reach out to connect to other cells.
Co-first author Dr Kobi Koffler, assistant project scientist in Dr Tuszynski’s lab, said: ‘The new work puts us even closer to real thing, 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.’
Co-senior author Dr Shaochen Chen used rapid 3D printing technology to create a scaffold that mimics central nervous system structures.
He said: ‘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 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 Dr Chen’s team produces two millimeter-sized implants in 1.6 seconds. Traditional nozzle printers take several hours to produce much simpler structures.
And the process is scalable to human spinal cord sizes, according to the research team.
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.
Co-first author Dr Wei Zhu, a nanoengineering postdoctoral fellow in Dr Chen’s group, said: ‘This shows the flexibility of our 3D printing technology.
‘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 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.
Dr Koffler 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.’
He said 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.
Dr Zhu added: ‘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.’
Now the scientists are 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.
The findings were published in the journal Nature Medicine.