ARPA-H fast-tracks historic regenerative breakthroughs to transform osteoarthritis care

Agency’s first program on accelerated path to eliminate osteoarthritis for millions of Americans 

The Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services (HHS), Novel Innovations for Tissue Regeneration in Osteoarthritis (NITRO) program is one step closer to eradicating osteoarthritis (OA) by enabling joints to heal themselves.  

OA affects 32 million Americans per year, costing the system more than $132 billion annually, and it is still one of the leading causes of disability in the United States. There is currently no cure, and most treatments today only manage pain or replace joints with artificial parts. Instead of just fixing worn-out joints with metal and plastic, NITRO teams are working to regrow real, living tissue, returning joints to their healthy state and eliminating evidence of disease.  

In two years, NITRO teams hit aggressive preclinical milestones, regenerating both cartilage and bone in osteoarthritic animal models. They are now working to complete the IND-enabling studies required to secure FDA concurrence to begin first-in-human clinical trials next year.  

Led by ARPA-H Program Manager Ross Uhrich, DMD, MBA, NITRO teams are reshaping regenerative medicine across all stages of the OA continuum with new approaches in the program’s three technical areas: targeted bone regeneration, targeted cartilage regeneration, and total knee implants composed of living human tissue.  

“Through ARPA-H, we are driving toward a future where people don’t have to wake up in pain, give up activities they love, or face major surgeries and repeat joint replacements — so they can stay active, independent, and healthy for longer,” said Alicia Jackson, Ph.D., ARPA-H Director. “NITRO’s progress helps damaged joints work again, slashes pain or even eliminates it, and aims to take the place of today’s joint replacement surgeries. NITRO is on track to transform osteoarthritis care for millions of Americans — we are moving from simply managing pain and swapping out worn joints to truly restoring natural movement, supporting longevity, and helping people live the lives they want.” 

“NITRO, ARPA-H's first program, was launched with the question: What if we could make our joints heal themselves? Two years later, it’s not only possible, but quickly becoming a reality,” said Ross Uhrich, DMD, MBA, ARPA-H NITRO Program Manager. ”As a leading cause of disability with myriad affiliated comorbidities, osteoarthritis is a multi-billion-dollar problem that requires regenerative cures rather than transient, reparative technologies. The teams and assets selected for continued funding in this historic phase transition have shown that we can regenerate tissue back to a non-OA state, prevent pain, drastically improve quality of life, and generate the treatment paradigm shift required to eradicate this disease.” 

For patients who have OA but don’t need a joint replacement, NITRO’s first two technical areas halt either bone and/or cartilage degeneration (alone or in tandem) and regenerate the joint back to its “native” healthy state through a one-time, single-stage injectable treatment. For patients who have OA and require a joint replacement, NITRO’s third technical area replaces traditional, titanium alloy artificial knees with a living, fully integrated implant that is seeded with either banked human (allogenic) or a patient’s own (autologous) bone and cartilage cells. This next-generation construct is fully loadbearing, non-immunogenic, capable of being remodeled and functionally engrafted into the body, requires no permanent fixation, and eliminates the need for repeat joint replacement. 

Uhrich added, "Every NITRO therapeutic is designed and priced for all Americans, particularly those most impacted by the disease, regardless of sociodemographic or insurance status. With first-in-human clinical trials only 18 months away, it’s clear that NITRO is positioned to change the future of osteoarthritis care for millions of Americans by eliminating this disability.” 

The NITRO teams’ revolutionary accomplishments include: 

• Duke University designed two injectable, time–released, combination drug formulations that stimulate bone and articular cartilage regeneration in OA-degraded joints. These therapeutics can be used alone or together. Duke researchers have also designed an intravenous time-release formulation that promotes targeted cartilage repair for patients with OA in multiple joints, eliminating the need for multiple injections. These therapeutics require only a single clinic visit, no more than once per year, to relieve joint pain and restore function by regenerating tissue lost to OA. An affiliated spinout company will commercialize these three products in a cost-effective way to ensure access for all Americans.  
• University of Colorado Boulder developed two new therapies that help aging or damaged joints repair themselves within weeks in animal studies. The first technology is a patented particle delivery system that is injected into the joint and provides intermittent bursts of a repurposed, regenerative drug for months. For patients with significant cartilage lesions, the second technology is a cocktail of engineered proteins that are injected arthroscopically and cured into place for focused regeneration. Renovare Therapeutics Inc. has been established as an independent company to commercialize their therapies quickly and accessibly. 
• Columbia University engineered a living, 3D-printed, human knee on a biodegradable scaffold that is infused with adult stem cells either from the patient’s own body (lipoaspirate from the abdomen) or from adult inducible pluripotent stem cells. After implantation, the cells regenerate the joint’s natural cartilage and bone tissues as the scaffold disappears. The new biomaterials allow the bone replacement structure to balance strength, ductility, and manufacturability using 3D printing. Columbia’s design mirrors the structure of current metal and plastic replacement joints, so surgeons can implant it using existing technologies and will have a higher rate of clinical adoption. NOVAJoint Orthopedics has been established as an independent company to commercialize their breakthrough technologies and make them accessible to all OA patients. 

Every NITRO team must follow strict clinical trial standards, including a program requirement that more than 50% of enrolled participants are women and trial participants reflect the populations most affected by OA, including American Indian and Alaska Native communities. As teams move to commercialization, ARPA-H provides tools and supports NITRO performer teams on transition plans to deliver affordable, accessible product(s), market-ready for all affected by OA. 

For more on NITRO, visit the program webpage.