Healing Gets a Leg Up

As a former point guard who pounded her knees on high school and college hardwoods, Kristi Anseth (PhDChemEngr’94) feels your pain.

As a CU-Boulder researcher in tissue engineering, she’s doing something about it.

The energetic 41-year-old CU distinguished chemical and biological engineering professor and her team of 30 engineers, scientists and students have spent a decade devising ways to put the spring back into the steps of aging, aching knees and hips. If their cutting-edge research with water-based materials proves successful in repairing joint cartilage, they could transform the way knee and hip problems are treated.

“Most people go to see their orthopedic surgeon when they experience a lot of pain from moving their joints,” says Anseth who is a Howard Hughes Medical Institute Investigator. “That means a lot of their cartilage has degenerated all the way down to the bone, which is tough to fix,” she says, explaining cartilage has a limited ability to heal.

As a result, injuries that took place years ago can come back to haunt you as you age. Take, for example, the knee you injured playing soccer when you were 20. By the time you hit 50, the small defect to your cartilage has grown larger and typically you need a total joint replacement.

Anseth and her team hope to intervene before patients need artificial hips or knees.

“We’ve been developing different types of biological materials that can help promote healing,” she says. “Hydrogels — Jell-O is a hydrogel — are basically materials that like water a lot but they don’t dissolve. They’re really good for a lot of biomaterial applications because our body has a lot of water.”

Putting gels to the test

This year, Cartilix, a California biotechnology company, tested Anseth’s hydrogels on 15 people in Europe. Most of the people in this study had significant degradation and would have undergone surgery. Instead, the patients’ cartilage cells were harvested and multiplied in a bioreactor, a device that cultures cells. Then, the company injected the CU-designed hydrogel into the patients’ knees via an arthroscopic procedure.

The hydrogel served as a “scaffold” upon which the cells grew and formed new cartilage to replace the cushioning that had deteriorated. The human test followed animal testing in which researchers injected the gels into three-year-old goats.

Preliminary reports from the study are very encouraging, albeit limited statistically with just 15 people involved. The six-month follow-up with MRIs shows good restoration of the filling, patients’ pain index is down and mobility is up.

But Anseth emphasizes the need to follow the patients over time. Her research team wants to know whether the repair will be stable and if it will be subject to degradation. To answer these questions, the Anseth team will raise funds for a larger trial involving several hundred subjects.

The Buffs’ head team physician Eric McCarty (Kines’88, MD’93), an all-Big Eight linebacker during his CU playing days, has been following Anseth’s research.

“This could be one of the next breakthroughs in treating cartilage problems,” McCarty, an orthopedic surgeon, says. “It has so much potential that you could utilize it on a weekly basis with the people we see.

“. . . The reason why people have to retire in pros or college is often a cartilage defect,” he says. “If [the hydrogel method] is found to be very effective in a clinical setting, it might be the go-to way to treat cartilage damage early on.”

The promises of tissue engineering

Anseth weighs the promise of tissue engineering against total knee and hip replacements, which work pretty well. Tissue engineering’s downside is regrowing cartilage is expensive since doctors need to do a biopsy to retrieve some of a patient’s cells, grow those cells in a bioreactor and then inject them into the body.

But getting a hip replaced, for example, has its negatives. The problem, she notes, is many people who suffer from pain delay surgery because they want the artificial hip to last their lifetimes. In effect, some people suffer for a decade in their 50s, experiencing intense pain when moving certain parts of their bodies.

Right now it’s not clear what’s going to be reimbursed by health insurance policies, but Anseth predicts this will change in time. And she says tissue engineers have bigger targets in their sights, such as heart valves. Anseth currently collaborates with professor Leslie Leinwand of molecular, cellular and developmental biology to develop replacement heart valves.

“Babies are born with heart valve defects and there’s no good solution,” she says. “They face multiple surgeries because they’re growing so fast. If you could design a heart valve that was a living, engineered tissue, it would have the ability to grow with the child and last a lifetime.”

Anseth is convinced that in her lifetime researchers are going to be able to develop a broad range of healing tissues.

“I have a 2-year-old daughter (Riley) and it’s amazing how fast she’s growing and developing,” she remarks. “How does a body know how to do that? I look at her and marvel about what the future holds for her. And I want to make certain that she can see what her mom did to try to make an impact, a difference in society and hopefully that will motivate her.”

Under the same roof

Making a difference forms the core emphasis of Anseth’s lab, which is a multidisciplinary hub of science where biologists, chemists, bio-engineers, chemical engineers and medical fellows have landed. Her team eventually will be housed in the pioneering Jennie Smoly Caruthers Biotechnology Building, which broke ground on east campus in September. The building will enable a multidisciplinary group of more than 60 faculty members and 500 researchers to collaborate on a variety of pressing human health problems from cancer, aging and cardiovascular disease to inherited diseases, vaccine development and tissue engineering.

“In some of [Nobel Laureate and CU chemistry and biochemistry professor] Tom Cech’s words, chemistry happens because molecules and atoms collide together with the right orientation and velocity,” Anseth says. “These types of productive collisions are exactly what we’re aiming for with researchers [in the new building] — unexpected events that may lead to profound new directions, collaboration and discoveries.”

To say Anseth is a rising star is a vast understatement, and she is credited for taking on the enormous task of bringing researchers from different scientific disciplines together to find solutions to human health issues.

“Until you’ve been in the middle of it or been on either side of it, it’s hard to really see the big gap between the biology and chemistry side of tissue engineering and how people will generally stay in their own field,” says Pete Mariner (PhDMCDBio’03), a doctoral researcher and Howard Hughes Medical Group lab manager who works with the Anseth group.

“Bridging that gap and being able to work somewhere between both fields is something most people don’t have the capacity to do,” he says. “Kristi not only has the capacity — she’s obviously succeeding.”