Biomedical engineers are collaborating with orthopaedic surgeons to build a living replacement knee which could be tested in clinical trials within the next five years.
A team of researchers from Columbia University Irving Medical Center (CUIMC) and Columbia Engineering has been awarded up to a $38.95 million contract from the Advanced Research Projects Agency for Health (ARPA-H) to build a living knee replacement from biomaterials and human stem cells, including a patient’s own cells.
ARPA-H is a federal funding agency that funds transformative biomedical and health research breakthroughs, rapidly translating research from the lab to applications in the marketplace.
The award, part of the ARPA-H’s Novel Innovations for Tissue Regeneration in Osteoarthritis (NITRO) program, will support the development of NOVAJoint, a revolutionary biocompatible, low-cost, patient-specific knee joint replacement.
This high-risk project builds upon more than two decades of collaborative musculoskeletal research at Columbia in engineering and medicine, and promises to offer a transformative solution for the more than 30 million people in the US who suffer from osteoarthritis. NITRO is the first Health Science Futures specific program under the new ARPA-H agency, established by the Biden Administration.
“ARPA-H is a hugely important endeavor that could bring about a breakthrough in personalised and patient-specific solutions,” said Shih-Fu Chang, Dean of Columbia Engineering.
“As society seeks to address the challenge of population aging, such collaborative approaches combining engineering and medicine will help improve conditions for those with osteoarthritis and many other musculoskeletal conditions.”
“We saw during the COVID pandemic just how fast science can move when teams of researchers are given the support and resources to work together,” said Katrina Armstrong, Dean of the Faculties of Health Sciences and the Vagelos College of Physicians and Surgeons, and Executive Vice President for Health and Biomedical Sciences, Columbia University.
“By focusing Columbia’s expertise in biomedical engineering and orthopaedic surgery onto a single goal, this funding from ARPA-H has the potential to rapidly revolutionize the way we treat osteoarthritis and the way we do biomedical research in the future.”
Impact of osteoarthritis
Osteoarthritis is a degenerative joint disease that is the most common type of arthritis. It gradually worsens over time as cartilage, the specialised connective tissue that covers the ends of bones, wears down, leading to pain, stiffness, and loss of mobility.
Osteoarthritis is already the third most common type of disability and has an estimated economic burden of more than $136 billion per year. It disproportionately affects women, the elderly, certain racial/ethnic minorities, and those with lower socioeconomic status. The prevalence of knee osteoarthritis has been rising due to aging of the population, increasing rates of joint injury, and, significantly, obesity.
The clinical gold standard treatment for knee joints ravaged by pervasive OA or traumatic injury is a total joint replacement using prosthetic implants made of metal and plastic. Although knee replacement is widely successful, there are some major drawbacks to these conventional materials.
There can be life-changing complications and limitations of current artificial knee replacements, including infection, loosening, hardware failure, stiffness, abnormal kinematics (i.e., the way a knee moves), instability, and persistent pain.
Historically, knee replacements have had a limited lifespan with a portion failing at 15 to 20 years due to plastic wear or implant loosening. This means that younger patients may need one or even two revision implants. The demand for total knee replacements is projected to grow by 673 per cent—3.48 million procedures from 2005 to 2030 —with total knee revisions projected to grow 601 per cent between 2005 to 2030.
NOVAJoint — a living solution to ravaged knees
With the ARPA-H award, the researchers propose to design NOVAJoint to address the urgent, unmet clinical need for a permanent solution for patients with advanced OA where a conventional knee replacement is indicated.
The project’s goal is to develop a replacement knee of regenerated living cartilage and bone that integrates seamlessly with the native bone and restores pain-free joint function. Since cells are required to regenerate and maintain this living implant, the team will create two versions of NOVAJoint: a version that uses patient’s own cells and one that uses donor cells.
The researchers expect NOVAJoint to substantially extend the implant life, reducing complications, and to become a permanent and final procedure for the treatment of osteoarthritis of the knee. With an aggressive timeline, in the first two years, the team will create the first prototypes before moving into preclinical and clinical studies in the final three years, including a Phase 1 safety clinical trial in the final year.
Though the first NOVAJoint is still in development, many of the technologies and scientific discoveries necessary to create the joint have already been developed and validated by Columbia researchers through funding from the National Institutes of Health, National Science Foundation, Department of Defense, and institutional support.
Clark T. Hung, a groundbreaking researcher in musculoskeletal regeneration, who is leading the project, said: “The ARPA-H NITRO program has enabled us to leverage our innovative technologies and expertise to solve one of the most difficult challenges in biomedical engineering,”
The project is led by Clark T. Hung, Professor and Vice Chair of the Department of Biomedical Engineering and Professor of Orthopedic Science (in Orthopedic Surgery) at Columbia Engineering, and Nadeen O. Chahine, Associate Professor of Biomedical Engineering in the Department of Orthopedic Surgery at Columbia University Vagelos College of Physicians and Surgeons, leaders in tissue regeneration and orthopedic research.