Researchers used cells to build and test a disc replacement with the strength and flex of a native disc, paving the way for human use.
The cells of a human could someday be used to help bioengineer a spinal disc in the lab to replace a deteriorated one causing neck or back pain. In a major step toward that direction, researchers have used cells to build and test a disc replacement in a goat that offers both the strength and flex of a native disc.
The spinal column is made up of a series of bones separated by soft-tissue intervertebral discs. Conventional replacement and spinal fusion—common treatments for degenerated or damaged intervertebral discs—do not fully restore the native disc’s biological function and range of motion. That’s bad news for about half the adult population in the United States, which suffers from back or neck pain at any given time at a cost of about $195 billion a year.
The research team, from the Corporal Michael Crescenz VA Medical Center (CMC VA) in Philadelphia, recently tissue-engineered a disc system and implanted it in the cervical spine of a goat, the largest animal model ever used for this purpose, according to a recent study in Science Translational Medicine. The goat’s cervical discs are similar in size to those of a human.
“Three decades ago, people started talking about replacing damaged or diseased human tissues with ones that we grow in the lab,” said Robert Mauck, professor for education and research in orthopaedic surgery at the Perelman School of Medicine at the University of Pennsylvania and a research health scientist at CMC VA in Philadelphia, and co-senior author of the paper. “This study shows how we can grow tissues in the lab, and then implant them into a large animal system.”
The team previously developed bioengineered discs, known as disc-like angle ply structures (DAPS), and studied them in the tail end of the rat spine for five weeks. This latest research extended that time period in the rat model—up to 20 weeks—but with an enhanced disc design known as endplate-modified DAPS, or eDAPS. The added endplates helped integrate the disc into the rat spine.
An intervertebral disc has two main structural features. The nucleus pulposus roughly resembles a sturdy water balloon that expands out radially when a load is placed on top of it. The annulus fibrosus functions like a tight rubber sleeve containing the outward expansion of nucleus pulposus.
To bioengineer a nucleus pulposus, the team began with a hydrogel-like material made of networks of water-swollen polymers and immersed it in a solution with stem cells and growth factors.
“When you add cells to this material, they will be viable and live there,” Mauck said. “This material provides a starting point for the tissue to grow and instructs how the tissue should mature. The cells slowly secrete extracellular matrix—the output of musculoskeletal tissue cells. The result is a formation of nucleus pulposus-like material.”
To recreate the annulus fibrosus in the lab, the researchers began with a biodegradable polyester immersed in a polymer solution and subjected it to a process called electrospinning.
“The result is a fibrous scaffold with a very precise organization at the micron-length scale,” Mauck said. “We pull these fibers into a very specific alignment to create a template with the structure and order that you would see in the native annulus fibrosus, which must be strong to resist the outward expansion of the nucleus pulposus. This material was also imbued with stem cells, which follow the organization of the scaffold template that directs how they pattern their extracellular matrix.”
The original DAPS design did not knit fully into the native spine, so the researchers engineered end plates made of porous foam. Before the engineered eDAPS is inserted into the spine, the native endplate was removed.
“By scraping away the native endplate, we can get to the bleeding bone underneath, allowing the cells of the bone of the vertebral body to access our device so they can grow together and anchor it in place,” said Harvey E. Smith, MD, an associate professor of orthopaedic surgery and neurosurgery at the Perelman School of Medicine and staff surgeon at the CMC VAMC, and co-senior author and clinical lead on the study.
After the rat model was immobilized for five months, the engineered disc was removed and tested by MRI, along with histological, mechanical, and biochemical analyses. The tests showed that eDAPS had restored the native disc structure, biology, and mechanical function of the native disc. The researchers next increased the size of engineered disc and evaluated it in the cervical spine of a goat. At eight weeks, the mechanical properties of the goat’s cervical disc either matched or exceeded those of the native disc. The researchers hope eventually to bring the device to limited early human trials.
Sarah Gullbrand, a postdoctoral researcher with the University of Pennsylvania and CMC VAMC, was first co-author. The study was supported by the U.S. Department of Veterans Affairs, the Penn Center for Musculoskeletal Disorders, and the National Institutes of Health.
John Tibbetts is an independent writer who focuses on new technologies.
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