Farshid Guilak, PhD, and his coauthors, Bradley T. Estes, PhD, and Franklin T. Moutos, PhD, received the 2021 Kappa Delta Elizabeth Winston Lanier Award for their research and development of technology to grow bioartificial cartilage using a patient’s own donor cells. The cells are seeded on a novel scaffold that can be molded to match the shape of a patient’s joint. Following a successful preclinical trial on canines with hip osteoarthritis (OA), the research is soon expected to begin a phase I clinical trial.
In addition, Dr. Guilak’s work in gene therapy to protect against joint inflammation has the potential to advance the treatment of patients with arthritis and some orthopaedic conditions.
“Due to injuries sustained from increased athletic activity and, conversely, a high prevalence of obese patients, we’re seeing more hip osteoarthritis in younger patients,” said Dr. Guilak, Mildred B. Simon Professor of Orthopaedic Surgery at Washington University and director of research at Shriners Hospitals for Children-St. Louis.
Although hip replacement is an ideal surgery for older patients, younger patients who receive a hip replacement will likely need revision surgery because the life span of the prosthesis is typically 15 to 20 years. “It is traumatic to tear out an old prosthesis, and the risks of infection and complications increase tremendously,” Dr. Guilak explained. “We wanted to find a way to restore hip joint function in the short term (five to10 years) until the time was right for a hip replacement.”
Drs. Guilak, Estes, and Moutos, along with numerous collaborators and colleagues, spent more than 15 years developing a scientific approach for extracting cells from the patient’s fat or bone marrow, combining them with a biomaterial scaffold, and establishing an optimal environment for the cells to multiply and form a living joint replacement.
“It is easier to fill a pothole rather than repave an entire road,” Dr. Guilak said. “With a background in bioengineering, we knew success was contingent upon a biomaterial scaffold that could not only hold cells but have the strength and durability to withstand joint loading after covering the entire joint surface.”
Over the years, the team tried hydrogels and nonwoven fabrics as the base for the scaffold, which proved too weak to withstand joint loading. Dr. Guilak and his research team then developed their own woven fabric using individual fibers of a safe and resorbable material. This allowed them to create a scaffold that was “porous enough to seed the stem cells directly into the fabric but strong enough to withstand loading compression,” he said.
After initial studies demonstrated the potential of this new approach, Drs. Guilak, Estes, and Moutos formed a startup company, Cytex Therapeutics, Inc., to translate this promising technology to treat young patients with joint disease.
To develop the cartilage, Dr. Estes worked to create optimal conditions to isolate the stem cells from either fat or bone marrow and then treat them with a cocktail of growth factors and supplements that allowed them to form into bone or cartilage-forming cells on the scaffold. The result is a living joint replacement that can restore the function of an osteoarthritic hip joint.
By implanting regrown cartilage started in a laboratory into the body to resurface a damaged joint, the stem cells continue to grow on a tough yet flexible scaffold, which will eventually disintegrate once the cartilage is fully developed.
This approach was tested in dogs with hip OA, and the implants showed success in all measured outcomes. As a result, the team expects to begin a phase I clinical trial for use in humans in the near future.
“We’re hopeful that as we work through this next chapter in our research, we can increase the efficacy of the joint replacement, so eventually it has a longer life span and one day could provide a permanent regeneration and replacement option,” Dr. Guilak said.
Dr. Guilak previously received the Kappa Delta Young Investigator Award in 1998 for “The Biomechanics of the Chondrocyte in Articular Cartilage” and was part of the team that received the 2015 Kappa Delta Ann Doner Vaughn Award for “Early Inhibition of Proinflammatory Cytokines Prevents Post-traumatic Arthritis: Insights from the Natural History of Arthritis Developing after Intra-articular Fracture.”
Dr. Guilak will receive his award Thursday at Your Academy 2021, 9:30 to 11:30 a.m., in Ballroom 20B.