The hip bone is connected to the thigh bone, the thigh bone is connected to the shin bone, the shin bone is connected. . . . So goes the old song, but what the lyrics don’t mention are the joints that connect all those bones or the pain that many of us experience in these necessary but relatively fragile body hinges.

Most of the 20 million Americans suffering from osteoarthritis are all too familiar with the paucity of treatment options, as are many of the rest of us who have injured a joint or who experience joint discomfort associated with aging. Most people just take anti-inflammatory drugs and learn to deal with the pain. But two research programs at Rice, both funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMSD), are attacking the problem from different angles and holding promise for more permanent relief.

What if osteoarthritis could be stopped before it started? That’s exactly what Kyriacos Athanasiou, a professor of bioengineering, hopes to accomplish through a tissue-engineering program aimed at growing replacement cartilage for those suffering from knee injuries.

His research centers on the meniscus, a kidney-shaped wedge of cartilage about the size of a man’s wristwatch. The meniscus fits between the rotating surfaces of the knee, cushioning the stress of walking and running by spreading the load over a wider area of the joint. This reduction of mechanical stress is critical because it is repeated mechanical stress in the joints that causes osteoarthritis, the form of arthritis that attacks most people as they age.

“Removing the meniscus creates a concentration of stress in a single spot in the joint, and that gives birth to osteoarthritis,” says Athanasiou.
But removing the meniscus often is necessary because once damaged, it can never heal. Some 750,000 Americans have all or part of a meniscus removed each year, primarily due to sports-related injuries and auto accidents. If surgeons could replace the damaged meniscus instead, they could reduce the chances for early-onset osteoarthritis in each of those patients.

During the past three years, Athanasiou and colleagues in Rice’s Musculoskeletal Bioengineering Laboratory (MBL) have established basic methods for growing cartilage in the lab via tissue engineering—a relatively new field that combines the latest techniques in bioengineering and biotechnology with the latest advances in materials science. The goal is to use a patient’s own cells to grow replacement tissue outside the body. The lab-grown organs and grafts can then be transplanted back into the patient without any risk of rejection.

Rather than growing slabs of cartilage and carving out meniscus-shaped pieces, Athanasiou and colleagues are attempting to grow the replacement meniscus in the exact shape needed. This marks the first time that researchers in any lab have tried to grow menisci in a predetermined shape, but Athanasiou says it is vital because doing so will allow the researchers to precisely simulate the conditions inside the knee during tissue growth. That makes it less likely that the replacement will fail once it’s subjected to the high-stress environment of the knee following implantation.

The five-year project received a $1.3-million grant from NIAMSD, which will fund four graduate students and one postdoctoral researcher at MBL and will cover the creation of methods to grow replacement menisci and in vivo testing of the replacements in rabbits. Project collaborators at Rice include Margaret French, postdoctoral research associate at MBL; Thomas Clanton, adjunct professor of bioengineering and chairman of orthopaedics at the University of Texas Medical School at Houston; Antonios Mikos, the John W. Cox Professor of Bioengineering; and Scott L. Baggett, senior statistician and lecturer of statistics at the Jesse H. Jones Graduate School of Management.

On another front, Antonios Mikos is leading an effort to develop biodegradable plastics that can be injected in place of damaged or missing cartilage, acting as a template for the regrowth of healthy cartilage.

Mikos’s research addresses a persistent and widespread problem: There is no synthetic alternative to human cartilage, which often is unable to heal itself following injury. As a result, millions of Americans suffering from arthritis and joint injuries have limited treatment options.

"Doctors can use grafts—either from the patient's own body or from donors," says Mikos. "Or they can perform surgery to encourage the body to regrow its own cartilage or to inject cartilage cells straight into the injury." However, most treatments involve surgery and, in many cases, the replacement cartilage is weaker and more susceptible to reinjury than native tissue. Mikos’s team hopes to develop new, noninvasive treatment options that eliminate the need for large surgeries and avoid associated problems such as tissue rejection and disease transmission. They envision doing this by harvesting a few of the patient’s own bone marrow cells and using those to grow more. These marrow cells will be included in a biodegradable polymer that is injected into the wound.

The polymer is administered as a liquid that turns into a semirigid gel after several minutes in the body. This semirigid filler, known as a scaffold, acts as a template for newly grown cartilage. The scaffold is designed to break down over time as new cartilage fills the wound.

There are several different kinds of cartilage in the body. Mikos’s research will focus on articular cartilage, the kind that covers the ends of bones in joints. The scaffold will be injected into the defect in the articular cartilage and seeded with adult precursor cells from the bone marrow. These undeveloped cells may become the type of cells found in cartilage in the presence of biochemical triggers found inside the joint.

A five-year, $1.7-million grant from NIAMSD will fund the studies. Ultimately, the group hopes to produce a two-layered scaffold that will promote cartilage formation in the top half and bone formation in the lower half.

—Jade Boyd