3-D Printed Implants Treat Spinal Cord Injury

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15 Jan. 2019. Customized implants, produced on a 3-D printer and seeded with stem cells, are shown in tests with lab animals to restore nerve signals and functioning after a spinal cord injury. A neuroscience and engineering team from University of California in San Diego describes its process and results in yesterday’s issue of the journal Nature Medicine (paid subscription required).

Spinal cord injuries are often caused by a sudden, traumatic blow to the spine that bruises or tears into spinal cord tissue, resulting in fractures or compression to vertebrae, or in some cases severing the spinal cord. Depending on severity, people with spinal cord injuries often suffer loss of feeling or motor function in the limbs, and in some cases complete paralysis. According to the National Spinal Cord Injury Statistical Center, spinal cord injuries occur in 54 out of 1 million people in the U.S., adding some 17,500 new cases each year.

A team led by UC-San Diego neuroscience professor Mark Tuszynski and medical engineering professor Shaochen Chen are seeking faster and more reliable treatments for spinal cord injury to regenerate and repair damaged nerve cells and tissue. Because of the complex nature of the spinal cord, progress on treatments for this condition is slow up to now.

Tuszynski, Chen, and colleagues devised a solution with an implant to repair the injury containing stem cells to regenerate new neurons, or nerve cells, seeded in a 3-D printed bio-friendly scaffold. The stem cells are precursors of mature neurons that transform and grow into functioning cells, particularly axons, the long thread-like extensions of neurons that send and receive electrical signals. Spinal cord injuries break or impair those electrical signals, resulting in loss of motor functions or paralysis.

The scaffold is made from hydrogel, a water-based polymer resembling natural spinal cord tissue. Chen’s lab studies micro- and nanoscale 3-D printing with biocompatible materials, particularly for stem cells, and for this application, used continuous projection printing, a process analogous to photo-lithography in producing semiconductors. The scaffolds were custom-designed based on MRI images of recipients’ spinal cord injuries, each 2 millimeters in thickness. Around the scaffold’s core are circular bins for holding the neural stem cells and micro-scale channels that direct the growth of the neurons and axons to optimize their healing effects.

“Like a bridge, it aligns regenerating axons from one end of the spinal cord injury to the other,” says Chen in a university statement. “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.”

Continuous projection printing is a high-speed process, which enabled production of each rat scaffold in less than 2 seconds. To prove the concept under more realistic clinical conditions, the researchers used continuous projection printing to produce implants modeled on MRI scans of human spinal cord injuries in about 10 minutes.

The researchers implanted the stem cell-seeded scaffolds in lab rats induced with spinal cord injuries. The results show the implants promote regeneration of nerve cells with axons extending into and integrating with the rats’ spinal cords. After a few months, spinal cord tissue regrew in the recipient rats, rejoining the severed sections. Blood vessels in and around the repaired spinal cords also were restored, enabling a return of motor functions in the rats hind limbs.

“In recent years and papers,” notes Tuszynski, “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.”

Chen and co-first author Wei Zhu, are founders of a spin-off enterprise Allegro 3D in San Diego. The company develops 3-D bioprinting technologies for replacement tissue and regenerative medicine, including for nerve cells.

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• Engineered Tissue-Polymer Replacement Spinal Discs Developed
• NIH Award Supports Esophagus Tissue Implants from Stem Cells
• Tissue-Engineered Heart Chamber Model Developed

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