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Getting your nerve back
Dr. Christine Schmidt and her research team engineer ways to speed nerve regeneration and recovery after injury

In an ad during the 2000 Super Bowl, the late actor Christopher Reeve is shown sitting at an award ceremony for research breakthroughs in spinal cord injuries.

When the announcer calls on the next person to present an award, Reeve stands up and walks the length of the stage to raise his arm and shake hands — things that, in reality, Reeve had not been able to do since a horseback riding accident left him paralyzed from the neck down five years prior.


Christine Schmidt
Biomedical engineering Professor Christine Schmidt's research on nerve regeneration has spanned 10 years, crossed engineering disciplines, garnered a patent and successfully bridged the path from lab to market. Now Schmidt and her students are applying this research to try and rebuild nerves damaged in spinal cord injuries.

The computer-animated commercial received praise and criticism of the actor best known for his role as Superman and, in his final years, as a quadriplegic and advocate for research on spinal cord regeneration.

Some critics lambasted the commercial for dramatizing what they considered only minimal advances in this area of research and for creating false hope for newly paralyzed people who might believe a cure was imminent.

Reeve, in his response to such critiques, was unfazed.

“It is a vision of what can actually happen," he said.

Fifteen to 20 years ago, spinal regeneration was deemed impossible, but today the outlook is generally more positive. That’s not to say the scientific community is close to finding a cure to spinal cord injury paralysis. Enormous progress must still be made. But a professor at the Cockrell School of Engineering is helping forge the way in spinal regeneration with research advancements that could benefit people with spinal cord injuries, injured soldiers, car accident victims and cancer patients.

Through research that has spanned more than 10 years, crossed disciplines, garnered a patent and bridged the path from the lab to the market by helping more than 3,000 patients, biomedical engineering Professor Christine Schmidt and her undergraduate and graduate students have developed promising ways to rebuild and restore damaged peripheral nerves — the nerves outside of the brain and spinal cord that connect to the central nervous system. The scientists are applying this research to try and rebuild nerves damaged in spinal cord injuries with hopes the developed methods will one day restore function and feeling to paralyzed parts of the body.

“There used to be a time when people thought spinal regeneration wasn’t a possibility and that’s not the case anymore. It is a possibility, but how do we do it?” Schmidt said. “If we can provide ways to give them more function, not walking necessarily, but even to control their bladder function, then that can brighten their outlook on life.”


A normal nerve and a stripped nerve
The predominant cause of rejection in a transplanted nerve graft is the dense fatty tissue, known as cellular lipids. Dr. Christine Schmidt and her students developed a cocktail of detergents that dramatically helps reduce the risk of transplant rejection by stripping the nerve of its fatty tissue, while maintaining the normal physical protein architecture of nerve. The image on the right shows a nerve once it has been through the stripping process. Images courtesy of Dr. Christine Schmidt and Dr. Terry Hudson
Rewiring and rebuilding a nerve

“How do we do it” is a big question.

To start with, nerves are dense fatty tissues with a delicate micro-architecture that is hard to preserve. The traditional way of repairing a peripheral damaged nerve involved replacing the nerve with one from elsewhere in a patient’s body. But this involves two surgical procedures and some loss of function still occurs, meaning a patient may get feeling back in his or her arm where initial nerve damage took place but it could be at the expense of losing feeling or function in the area where the replacement nerve was removed. The predominant cause of rejection in this kind of transplant is the nerve’s own fatty tissue, known as cellular lipids.

To get around this, Schmidt and her students developed two methods, the first of which replaces a damaged nerve with a nerve from a donated cadaver. Over the course of four years, Schmidt and her students developed a cocktail of detergents that helps strip the donated nerve of its fatty tissues so that the odds of rejection are dramatically reduced once transplanted into a patient’s body. The stripping process was patented and one of Schmidt’s graduate students, Terry Hudson, is listed as co-inventor of the technology.

In 2004, Schmidt published results on the research from animal studies. The findings caught the attention of a Florida-based company, AxoGen, which contacted her and eventually licensed the stripping technology. The company created a transplant tissue called Avance®, which it provides to surgeons as a graft for injuries to peripheral nerves, such as those suffered during a car accident or surgery for pancreatic cancer. The company also hired students who worked on the research under Schmidt.



Synthetic nerve
Schmidt and her students built the synthetic nerve pictured above. The method uses a laser-based lithography approach to create gradients of different molecules that replicate the natural biochemical composition of a nerve. Image courtesy of Dr. Christine Schmidt, Dr. Shaochen Chen and Dr. Shalu Suri

Avance has been used in more than 3,000 patients with peripheral nerve injuries, Schmidt said, and now her technology is being evaluated for its potential to aid repair of nerves in injured spinal cords.

The biggest hurdle to repairing spinal cord injuries is that the nerve’s natural pathway to the brain is disrupted and then blocked by dense scar tissue at the area where the fracture or trauma occurred. Something as seemingly basic as a nerve in the intestines communicating with the brain over control of bowel or bladder function is derailed by the injury, and repair is prohibited by the scar tissue.

Working with Schmidt and her students and using the nerve grafts they created, a neuroscience professor at Case Western Reserve University in Cleveland is producing a way to bypass the scar tissue and create a new route for nerves outside of the spinal cord so they can communicate with the brain as they should.

The professor, Jerry Silver, produced the research with one of Schmidt’s postdoctoral students and results from the pilot data are expected in February.

Schmidt and her students are still in the early stages of their second approach to nerve repair and regeneration in the spinal cord. This method, while more complex to engineer, could be less expensive and less labor intensive in the long term, easier to manipulate and have a greater impact.

It involves building a nerve with synthetic molecules that conduct electricity and naturally derived sugar molecules, known as hydrogels, which are found in the body. The method uses a laser to draw synthetic lines that mimic the micro-architecture of a nerve.

On the surface, these advancements in nerve regeneration may seem small. But if we can give a person with a severe spinal injury the ability to control a basic function like when they go to the bathroom, then we are giving them a huge part of their life back. Dr. Christine Schmidt

Because this method uses artificial materials, it’s much more difficult to gain approval for use in the U.S. Food and Drug Administration’s lengthy and complex review process, Schmidt said.

Although greater progress is needed, the prognosis for spinal cord research in general has become more positive, Schmidt said, and she expects a combination of pharmacological, rehabilitation and biomaterials will eventually be successful. Research now focuses on restoring function of individual organs, rather than the entire spinal cord at once.

Schmidt knows any seemingly small advancement can brighten the outlook for people with spinal cord injuries.

Part of what made her want to study biomedical engineering was her fascination with the cell’s ability to move throughout the body on its own, and the body’s ability to coordinate the migration. She’s also inspired for more personal reasons.

During graduate school, a quadriplegic woman lived down the hall from her and she’s known several people with spinal injuries, including a man whose wife also took on the role as caretaker for her husband.

“On the surface, these advancements in nerve regeneration may seem small,” Schmidt said. “But if we can give a person with a severe spinal injury the ability to control a basic function like when they go to the bathroom, then we are giving them a huge part of their life back.”

By Melissa Mixon
Cockrell School of Engineering