Hybrid Tissues for Stubborn Injuries

By Gene Charleton

Developing hybrid tissues to help rebuild body parts that might otherwise be beyond repair.

It’s a long step from the latest generation of jet airliners or an earthquake-resistant office building to a blown-out ACL in your knee or a clogged artery in your heart; aircraft and buildings don’t seem to have much in common with ligaments and blood vessels.

Unless you’re an engineer.

For biomedical engineer Elizabeth Cosgriff-Hernandez, applying the same engineering principles to building new tissues for ligaments and blood vessels that her colleagues in other engineering specialties use to design airplanes or buildings makes perfect sense.

Cosgriff-Hernandez is one of a new breed of engineers who are developing new methods and materials that one day will help our bodies heal better and more quickly than before.

“Tissue engineering aims to bridge the gap between organ transplants and medical devices,” says Cosgriff-Hernandez, an assistant professor in Texas A&M’s Department of Biomedical Engineering. “We want to combine what the body knows how to do with natural materials with the mechanical properties, availability and tunability of synthetic materials.”

Take the anterior cruciate ligament (ACL), for example, the cordlike ligament that holds the knee joint in position. If you follow collegiate or professional sports, you know that athletes damage their ACLs with painful frequency. Treating a ruptured ACL almost always involves replacing it with tissues taken from elsewhere in the body or transplanted from a cadaver. Both approaches work, but neither is perfect.

Research turns personal

One of Cosgriff-Hernandez’s major research efforts is developing a synthetic replacement for an injured ACL that will support the injured knee while the body is being nudged to grow a new ligament. It’s more than an interesting research project: It’s personal. She knows firsthand what’s involved in repairing a torn ACL. She tore her ACL in a collision with another player during an Ultimate Frisbee game.

"We want to combine what the body knows how to do with natural materials with the mechanical properties, availability and tunability of synthetic materials."

The approach Cosgriff-Hernandez and her students are taking to the ACL problem runs along several parallel tracks. They’re investigating new synthetic materials, understanding the role of stem cells in the body’s healing process and how to manipulate them to guide the growth of new tissue to replace damaged tissue, and understanding and using the biochemical and biomechanical cues that guide the development of stem cells and other tissue cells.

The basic material in Cosgriff-Hernandez’s ACL-rebuilding blueprint is polyurethane, a strong, flexible and biologically inert plastic. She studied urethane while completing her Ph.D. degree and is intimately familiar with its properties. Braided into a cord of the right thickness and length, polyurethane is strong enough to keep the knee stable. But that’s only the first step in Cosgriff-Hernandez’s plan. She says she sees the polyurethane cord as a scaffold to provide support while the body itself replaces the damaged ligament.

“We want to have a ligament scaffold that can replace the function of natural ligament as long as it’s needed, not permanently,” she says.

This is where the project gets complicated.

As Cosgriff-Hernandez sees it, she and her students are trying to balance the need for a strong, temporary, artificial replacement ligament against the equal need for the body to produce a strong, permanent, natural replacement ligament.

“When you think of scaffolding on a building that’s being repaired, it’s the framework for the construction guys to build or repair the building,” Cosgriff-Hernandez says. “Then, just as the scaffolding comes off the building when repairs are completed, you want the scaffolding to go away so eventually you don’t have anything but the building, the native tissue in what we’re doing.”

Timing tissue breakdown

Making this idea work means designing both an artificial polyurethane ACL and a complex physical and biochemical process that balances breaking down the artificial ligament, the scaffolding, at the same rate that the body builds new ligament. If the scaffolding breaks down too fast, the rebuilt natural ligament won’t be strong enough to handle the physical stress of keeping the knee stable. If it breaks down too slowly, the replacement ligament won’t get the biological and mechanical cues it needs to develop properly.

"We’re at a really good, really exciting place right now. We have the lab established, we have the students trained. It’s a pretty good place to be."

This concept requires new developments in building the urethane material needed for the temporary replacement ligament and in manipulating stem cells that will develop into cells of ligament tissue.

The plan is to use the polyurethane ligament as a scaffold, or framework, to hold stem cells in the shape of the ACL so that when the stem cells receive the right biochemical cues, they will transform themselves into cells that create the replacement ligament. As the new ACL begins to develop, cells generate protein-cutting enzymes that break down the polyurethane when they receive the right biochemical cue. Done in the right place at the right time, this breakdown will allow the newly produced natural ACL tissue to take the load of keeping the knee in the right position from the polyurethane replacement ligament.

“As the cells regenerate the tissue, they break down the scaffolding material and eventually get rid of it, and all you have left is the native tissue,” she says. “Ultimately, we want to have a ligament scaffold that can replace the function of the ligament and then have it degrade at the rate the cells dictate, so that the cells can lay down new matrix.”

Research at double time

Researchers all over the world are making progress so fast in stem cell research that Cosgriff-Hernandez says she is confident that the understanding of biochemical cues and pathways needed to transform stem cells into new ligaments will be here when she needs it.

“What we thought we knew for sure five years ago, even two years ago, people are overturning,” she says. Even with this rapidly developing understanding of stem cells, getting from where Cosgriff-Hernandez and her colleagues are now to a successful ACL replacement is going to be a complex and difficult undertaking, but she is confident they’ll get there.

“We’re at a really good, really exciting place right now,” she says. “We have the lab established, we have students trained; they’re really productive, they’re really enthusiastic and engaged, and we have people interested in our materials and collaborations, so it’s a pretty good place to be.”

Working with colleagues in Texas A&M’s Artie McFerrin Department of Chemical Engineering, Cosgriff-Hernandez is using approaches similar to her work toward artificial ACLs to shape similar scaffolding that will shape artificial blood vessels that could replace arteries blocked by cholesterol or blood clots. The issues with them are much like those involved in her ACL-related research: providing a three-dimensional scaffold for tissue cells to grow on to produce a functional organ.

“Just walking up and down the halls here in the department is fascinating,” she says. “Almost everyone who’s doing research has a personal story about people they know personally that their research could one day benefit.”

A colleague’s husband, for instance, is diabetic. Part of her research is aimed at making insulin therapy for diabetes more effective.

“I would like to see, in my lifetime, something that I worked on or contributed to helping someone live better and longer,” she says. “I think that would be ultimate success for me.”