Room for Many More
OREF grant recipient investigated ways to make meniscus transplants more successful
With an OREF Clinician Scientist Award, Cristin M. Ferguson, MD, researched easier and longer-lasting ways to replace the structure in the knee responsible for stability and cushioning. Her grant was funded by a contribution to OREF from The Journal of Bone and Joint Surgery.“It is very easy to have all your research time taken up by clinical practice,” Dr. Ferguson said. “You add on a surgery. You add on a clinic. It’s very hard to carve out research time, and that’s what this award enabled me to do. It helped develop the research part of my career and freed some time so I could serve as a mentor to people who have similar interests.”
Getting to the Center
Dr. Ferguson’s research concerned the meniscus, a C-shaped cartilage cushion that acts as a shock absorber and stabilizes the knee. One of the most common procedures performed by orthopaedists, according to Dr. Ferguson, is knee arthroscopy to manage damaged cartilage structures. And the majority of these, Dr. Ferguson said, involve the trimming of torn menisci instead of repair, which has long-term implications for the knee.
“One of the more difficult things to see in your practice is a young, active person whose knee is, overall, very healthy, but they have a cartilage tear that can’t be fixed. Often a substantial portion of the injured meniscus needs to be removed because it is biologically and mechanically unable to heal,” Dr. Ferguson said. “Although current meniscus transplants with cadaver tissue are good, there are certain biological aspects that lead to earlier failure. They do not all appear to function as well as the original meniscus and they do not appear to last as long.”
Dr. Ferguson sought a solution to this problem, which she believes is caused by the nature of the cadaver transplant tissue.
“Studies show that the recipient of the transplant, or host’s, cells cannot grow into the central portion of the transplant, which is a dense tissue. Ultimately there are no cells living in the central portion of the transplant to help maintain its structure and strength, so it wears out.”
To prevent this problem, Dr. Ferguson investigated a way to transplant menisci with living cells in the center. Her research involved chemically processing cadaver menisci to not only remove the cadaver cells, but also create spaces (porosity) for new cells to grow. She believed that would give the host’s cells room to grow into the center of the allograft.
An Amenable Allograft
In addition to making room for the host’s cells, Dr. Ferguson worked on another process to help the transplant patient accept the allograft. By deriving stem cells from the host’s own blood or bone marrow and inserting them into the transplant tissue, Dr. Ferguson aimed to create a meniscus that was already populated by the patient’s own cells before the transplant took place.
“I think the thing that is attractive about this method is that the fundamental structure of the meniscus—the natural arrangement, structure, and composition of collagen fibers—is maintained. We aren’t trying to synthetically reproduce the meniscus. It is a complex tissue that would be very difficult to accurately recreate with synthetic materials. Instead, we’re preserving the natural structure, but making it more biologically compatible for the body‘s cells to grow in and take over. The ingrowing cells can also take cues from the surrounding collagens and proteins to guide them to grow into the desired tissue. We’re capitalizing on the complex structure and biology of the meniscus scaffold that’s already there by making the allograft tissue more amenable for our bodies to incorporate and maintain it.”
The idea behind this, according to Dr. Ferguson, is that the living host cells that grow into the center of the tissue upon implantation should be better able to maintain the collagen and surrounding matrix proteins and, therefore, maintain the structural integrity of the meniscus tissue transplant. The fact that the host cells are added to the allograft also helps the recipient’s body accept the tissue because it already seems like the patient’s own.
These studies could have additional implications for older patients. As people age, the meniscus degenerates, and Dr. Ferguson would like to further her research by studying the processes of aging in the meniscus.
“Concurrent with meniscus degeneration, we also see the development of arthritis, and although the articular cartilage research that’s currently being done is very important, I think we’re missing information on another very important structure within the knee that contributes to the development of arthritis: the meniscus,” said Dr. Ferguson. “We need to understand the biology that is happening in the meniscus with aging and development of degenerative changes.”
Hope for Healthier Knees
In addition to the OREF award, Dr. Ferguson received funding from the Musculoskeletal Transplant Foundation, National Football League Charities and a National Institutes of Health K08 Award to support her meniscus transplant research. She currently holds a patent for “Tissue engineered meniscus scaffolds and methods of use” as a co-inventor with Mark E. Van Dyke, PhD.
Dr. Ferguson hopes that this technique could someday be used to help patients who’ve experienced more extensive cartilage and arthritic injury than what is currently managed with standard meniscus allograft transplantation. “I’m trying to work on the current technique to make it better so that patients will have better results with better long-term function. By creating a healthier knee, patients can stay active longer, especially in their younger years, doing all of the activities that they like to do instead of giving them up.”
Dr. Ferguson believes research is important, not only because she is a clinician scientist, but also to advance orthopaedics.
“There are so many things that I do every day that seem to work in clinical practice, but I don’t really understand them. I’d like to understand why people tear their meniscus. I’d like to understand why the meniscus wears out. Research allows me the opportunity to ask these questions and, over time, answer them. I think the ultimate goal is to expand our knowledge so we can better treat patients.”
Dr. Ferguson has focused her medical career around orthopaedic clinical training, sports medicine fellowship training, and basic-science orthopaedic research. She spent more than two years conducting orthopaedic research during her training, first at the University of California, San Francisco, and then at the University of Rochester. In 1999 she received an OREF Resident Research Grant for her study of the process of cartilage maturation. Currently, Dr. Ferguson is an assistant professor of orthopaedics at the Institutes for Regenerative Medicine, Wake Forest Baptist Health, Winston-Salem, N.C.