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Knee osteoarthritis (OA) is a mounting health crisis that impacts an estimated 32.5 million people in the U.S. and 500 million people worldwide. The common degenerative joint condition remains a significant issue because current treatment options are less than ideal.
Prescribing opioids to relieve chronic pain in OA sufferers is not an effective long-term solution and carries risks of addiction and other health-related issues. Joint replacement surgery is the current gold standard of care, but the recovery process can be grueling and prosthetic implants are limited to lifespans of about 20 years.
Researchers at Case Western Reserve University (CWRU) are working on providing a longer-lasting and more effective solution with “live” replacement joints built from human cells. They believe the load-bearing joints would reverse the damaging effects of OA and restore natural joint function to relieve chronic pain and mobility difficulties.
Replacement joints built from human cells would do away with permanent plates and signal the formation of new bone and cartilage. The body’s immune system would accept the live joints, creating a permanent solution that eliminates the need to replace implants that fail over time.
Ozan Akkus, Ph.D., the Kent Hale Smith Professor of Engineering and a Professor of Mechanical and Aerospace Engineering at the Case School of Engineering (CSE), said the research project will involve an orchestrated engineering approach in which load-bearing biodegradable structural components are cellularized with autologous or allogeneically-derived cells, conditioned in bioreactors and implanted in patients in a way that is comparable to current surgical techniques.
“Controlled degradation of structural components and their synchronous replacement with appropriate bone and cartilage in specific sites will be the key,” said Dr. Akkus, who is also the Director of CSE’s Tissue Fabrication and Mechanobiology Lab. “The materials that we will use are known to be biocompatible.”
Dr. Akkus and his colleagues are focused on engineering a living replacement component for arguably the most complex joint in the human body. “Success at knee reconstruction would be a stepping-stone to applying the technology to the hip, shoulder and other joints, large or small,” he said.
Individuals with expertise in materials science, structural design, cell processing and preclinical testing are in place on the research team. Dr. Akkus acknowledged the challenge of coordinating these diverse disciplines to develop the first blueprint of a commercially viable process in which regenerative engineering will be applied to an entire joint.
The researchers want to scale the technology to make it commercially available to patients by 2029. Dr. Akkus noted that the research team includes equity experts who will study demographic disparities in OA treatments and identify reimbursement challenges. He also pointed out that CWRU has successfully developed numerous biomedical technologies, because Northeast Ohio is home to several major medical centers.
“Our team will be keeping commercialization and a fundamental cost analysis in focus and running in parallel to technical R&D activities,” Dr. Akkus said. “Any solution that gets the job done but comes at an exorbitant cost will be scrapped.”
He expects that coordinated efforts among members of the research team will focus on the cost of the technology at all times, and the economy of scales in future commercialization will market the living knee joint concept at a realistic price point.
“Every person I speak to about this project suffers from OA or has a friend or family member who is affected,” Dr. Akkus said. “The possibility of helping a significant number of people is our biggest motivation.”
He is especially excited about offering a solution to younger OA patients who will not require a revision implant for the rest of their lives.
“Giving people their mobility back, with a living joint that feels like their own, while addressing the chronic pain they endure will fuel our efforts,” Dr. Akkus said.
The project is supported by the “OMEGA: Orchestrating Multifaceted Engineering for Growing Artificial Joints” award from the Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services that focuses on transformative biomedical and health breakthroughs. CWRU received $20.4 million upfront and will receive another $27.3 million if certain research milestones are met. The researchers have proposed implanting live joints in 40 patients within five years.
ARPA-H accelerates improved patient outcomes by supporting the development of high-impact solutions to society’s most challenging health problems. The agency advances biomedical and health research that cannot be accomplished through traditional research or commercial activity.
CWRU’s work is part of ARPA-H’s Novel Innovations for Tissue Regeneration in Osteoarthritis (NITRO) program, which addresses treatment of OA by developing new ways of helping the human body repair its joints.
“The ultimate mission,” said Michael Oakes, Ph.D., CWRU’s Senior Vice President for Research and a professor at the CWRU School of Medicine, “is to address the failures and limitations of current treatments by developing a safe and effective living joint that lasts a lifetime in the patient’s body.”
