For the first time, researchers have utilized 3D printing technologies to create a spinal cord, which has been successfully implanted and loaded with neural stem cells to promote nerve cell growth for spinal cord injuries.
The implants are intended to promote nerve growth across spinal cord injuries, restoring connections and lost function. In rat models, the researchers revealed that 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 results of the study have been published in Nature Medicine.
Shaochen Chen (University of California San Diego [UCSD], CA, USA), co-senior author of the study, commented: “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.”
According to the researchers, the implant contains dozens of tiny, 200-µm wide channels that guide neural stem cell and axon growth along the length of the spinal cord injury. The printed technology used by the team produces 2-mm-sized implants in 1.6 seconds, whereas traditional nozzle printers are reported to take several hours to produce much simpler structures.
The researchers believe that the process is scalable to human spinal cord sizes, and as proof-of-concept, they printed 4-cm-sized implants modelled from MRI scans of actual human spinal cord injuries. These were printed within 10 minutes.
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“This shows the flexibility of our 3D printed technology,” said co-first author Wei Zhu (UCSD). “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 2-mm implants, which were loaded with neural stem cells, into sites of severe spinal cord injury in rats. After a few months, they demonstrated that new spinal cord tissue had regrown completely across the injury and connected the severed ends of the host spinal cord. Additionally, they reported that treated rats regained significant functional motor improvements in their hind legs.
“This marks another key step towards conducting clinical trials to repair spinal cord injuries in people,” stated Kobi Koffler (UCSD), co-first author of the paper. “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.”
One of the main hurdles in engineering tissue implants that can last in the body for a long time is vascularization. 3D printed tissues need vasculature in order to receive enough nutrition and to discharge waste. However, the research team managed to overcome this, as the circulatory system 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 regrowth.
Sources: Koffler J, Zhu W, Qu X et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Nat. Med. doi:10.1038/s41591-018-0296-z (2019) (Epub ahead of print); https://health.ucsd.edu/news/releases/Pages/2019-01-14-three-D-printed-implant-promotes-nerve-cell-growth-to-treat-spinal-cord-injury.aspx