Repair, Regrow, Regenerate

It is somewhat miraculous, the wonders that nature can work. 
 
Axolotl salamanders, for example, can regrow their spinal cord, heart and limbs. Many crab species can regrow claws. And a chopped-up panther worm can completely regenerate from each segment. 
 
The human body can do a lot, too, knitting skin and bones back together after an injury. But there are limits. Sever the spinal cord, for example, and the damage is almost always permanent. 
 
But Northwestern researchers, including Samuel Stupp, Guillermo Ameer and John Kessler, are on the cusp of some superhuman breakthroughs, pushing the body’s boundaries through advances in regenerative medicine and engineering, with the goal of bringing healing and hope to countless people. 
 
Over the past year, Stupp ’77 PhD has heard from thousands of people who have seen the stunning effects of his latest regenerative therapy, including many who have suffered spinal cord injuries as a result of car accidents and gunshot wounds. 
 
“Not once in 15 years, in all my time spent looking for a way to fix me, has any [research] given me the amount of hope that this one has,” one note said. 
 
The videos of Stupp’s therapy, posted in 2021, speak for themselves. In the first, a mouse paralyzed by a severe spinal cord injury drags its back legs. In the second — after receiving Stupp’s injectable therapy — a previously paralyzed mouse moves its back legs, crawling almost normally across the floor. (See video below.) 

For the nearly 300,000 people living with spinal cord injuries in the United States, modern medicine has offered little treatment beyond physical therapy. But Stupp’s breakthrough might finally offer a ray of hope. 
 
For Stupp, the results of the therapy are the culmination of more than two decades of work in regenerative medicine. In fact, in 2008 Stupp first saw mice regain a limited ability to walk after their moderate injuries were treated with a much earlier version of the therapy, the result of a collaboration with Kessler. 
 
But repairing parts of the body that do not regenerate on their own is extremely complex. It requires a deep understanding of materials science, biology, chemistry and the complicated networks that govern healing and regrowth. Stupp and members of his lab have been refining that knowledge over the past decade, trying to create new materials that could spur robust regeneration in different parts of the body. 
 
So when Stupp saw his new bioactive material harness the motion of thousands of molecules, making the therapy much more effective, he was surprised and excited. And when he published his research in the journal Science in November 2021, and the letters came pouring in, asking when clinical trials would be available, he understood just how desperate people were. 
 
“I never expected there would be this kind of response,” says Stupp, the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering. “It has been truly overwhelming. It allowed us to become keenly aware of the need, that this therapy could have a huge impact.” (Listen to Stupp describe his research.) 

Interdisciplinary Roots

It’s been a journey to get to this point. As a boy growing up in Costa Rica, Stupp immersed himself in the science books his father brought back from business trips to the United States. Both of his parents had fled Eastern Europe as children in the tumultuous years before World War II, and they encouraged him to take advantage of every opportunity to succeed in their adopted country. 
 
When his father developed the first record manufacturing facility in Central America, Stupp began to learn about the electrochemistry needed to make the metallic molds and the science behind the records’ polymeric materials. 
 
Stupp traveled to the U.S. and attended UCLA for his undergraduate degree in chemistry and then earned his doctorate in materials science and engineering at Northwestern. He first joined the Northwestern faculty in 1977 as an assistant professor of biological materials. He left in 1980, and by the time he rejoined the University faculty in 1999, he was beginning to explore the use of nanostructures to spur the body’s repair process. 
 
Using his cross-disciplinary interests, he ultimately forged a career that spans materials science, chemistry, biology and medicine. 
 
Stupp’s spinal cord therapy is a type of biomaterial, meaning it is designed for use in living systems. Made from synthetic or natural materials, biomaterials can be used in permanent implants, in materials for drug delivery and as scaffolds for tissue regeneration, among other applications. Stupp and his lab have developed a broad platform of biomaterials that can send signals to cells, instructing them to do specific tasks needed to rebuild tissue and promote healing. 
 
These new nanofibers deliver two distinct signals that trigger different aspects of spinal cord repair. One signal prompts the long tails of neurons in the spinal cord, called axons, to regenerate and also reduces scarring, which acts as a physical barrier to regeneration. The other signal stimulates the growth of lost blood vessels, rebuilds myelin (the insulating layer around axons that helps transmit electric signals) and promotes the survival of motor neurons. 
 
The biomaterials contain building blocks that naturally exist in the body, and after they’ve induced growth and healing, they biodegrade with no side effects. 
 
Stupp, director of the Simpson Querrey Institute for BioNanotechnology at Northwestern, hopes to bring this spinal cord therapy to clinical trials within a few years (see “Spinal Cord Therapy: What’s Next?” sidebar), and in the meantime he is designing the materials for use in other organs and tissues, including bone, cartilage, muscle and kidneys. He also believes the breakthrough in spinal cord injury research is directly relevant to other key targets in central nervous system repair, including stroke, brain injury and neurodegenerative diseases. 
 
This discovery was the result of more than 20 years of work across disciplines in the Stupp lab. “Regenerative medicine is the ultimate example of interdisciplinary research,” Stupp says. “You need to integrate physics, chemistry, biology, engineering, materials science and medicine. 
 
“I am extremely grateful for the support I received from Kimberly Querrey and the late Lou Simpson ’58 to undertake this challenging and important interdisciplinary research at Northwestern.”