Can scientists literally grow an implantable hip replacement?
One group at Washington University in St. Louis appears to have made excellent progress doing exactly that with a novel, woven 3D scaffold and living cell system.
Farshid Guilak, Ph.D., a professor of orthopedic surgery at Washington University in St. Louis and the director of research at Shriners Hospitals for Children St. Louis, is on the forefront of these efforts. He told OTW, “Prostheses don’t always survive…and when they don’t, revising them can be very complex. I set out to find a way to delay—or even prevent—a traditional joint replacement surgery.”
To help give surgeons and patients more options, Dr. Guilak founded Cytex Therapeutics, Inc. “I wanted to have a startup company that was run separately from our academic research lab, and that could develop the translational side of the project. Now, at Washington University, we are collaborating with Cytex to conduct basic science research in our academic lab and will go on to do studies that will take this into preclinical models.”
In what is essentially a new way to resurface an arthritic joint, Dr. Guilak and his team have programmed stem cells to grow new cartilage…and to do so on a 3D template in the shape of the ball of a hip joint. And taking things even further, they have made use of gene therapy to encourage the newly grown cartilage to release anti-inflammatory molecules. “We developed a 3D synthetic scaffold that is completely biodegradable (similar to a resorbable suture). There are 600 fibers that are woven together to create this 3D fabric that is then molded into the shape we want.”
Franklin Moutos, Ph.D., vice president of technology development at Cytex, explained that the unique structure of this high-performance fabric gives it the properties of normal cartilage. “As evidence of this, the woven implants are strong enough to withstand loads up to 10 times a patient’s body weight, which is typically what our joints must bear when we exercise.”
Dr. Guilak notes, “It is a different concept than 3D printing. With 3D weaving, the material can be designed to be tough in one direction, but flexible in another direction (like cartilage). We selected to work with the hip first because it is a straightforward shape (a hemisphere). The knee is more complex because there are three bones to deal with (and a myriad of connecting ligaments).”
“The porous scaffold is in the exact shape of any given patient’s joint, and is covered in cartilage from the patient’s own stem cells. Surgeons can then take the scaffold and put it onto the surface of an arthritic hip or knee.”
“The cells are a variety of adult stem cells, either from subcutaneous fat or bone marrow. Working in an arthritic environment has proved challenging, as inflammation can break down new cartilage the same way it breaks down native cartilage. To address this, we used gene therapy to modify the cells so that they produce (on demand) an inhibitor of interleukin 1, a potent inflammatory molecule. This gives you a built-in drug delivery system that can be turned on and off. Early on, such as shortly after an injury, a bit of inflammation is necessary for the repair process, but over time the inflammatory response needs to die down. So we need to determine when exactly to turn on and off this mechanism. We will finish the initial animal study in about six months and if the results are positive then we will begin to put together a long-term, FDA pivotal large animal study; in two to three years the results from that work should be available.”
“One of the important questions that an animal study can address is whether this type of approach can relieve pain and restore the function of the hip joint that is injured or arthritic.”
Bradley Estes, Ph.D., vice president of research and development at Cytex, noted, “We envision in the future that this population of younger patients may be ideal candidates for this type of biological joint replacement.”
“For our method to be useful, it needs to result in a postponement of five to ten years in joint replacement surgery. This is most definitely a worthwhile option given that it is less invasive than traditional joint replacement and it leaves the bone intact. And it could be particularly useful in patients under the age of 50 as surgeons are more cautious about hip replacement in these patients.”
“One benefit of this work is that it provides a way for the joint to support rapid and heavy loading immediately. It takes time for the cells to make cartilage and then they need a place to engraft, where they can regenerate the cartilage layer in the joint. Unfortunately, if you just inject the cells, most of them are gone in a few days.”
This research, the results of which appear in the Proceedings of the National Academy of Sciences, means that millions of arthritis sufferers could experience a lessening of their daily pain and get out there and live their lives. Dr. Guilak, who also is the director of research at Shriners Hospitals for Children–St. Louis, and co-director of the Washington University Center of Regenerative Medicine, has tested various aspects of the tissue engineering in cell culture, and some customized implants already are being tested in laboratory animals. Dr. Guilak and his team estimate that they will reach the human testing stage within the next three to five years.
Article available at: http://www.pnas.org/content/113/31/E4513.abstract
