CAMEO: The orthopaedics engineering center changing medicine

Rolling Pocono mountains, lukewarm gas station coffee, and skyward towers suspending the George Washington Bridge above the Hudson—this is what changing the medical world looked like to Donald Bartel as he made countless drives from Ithaca to Manhattan. He wasn’t going to let a mere 229 miles get between him and a brilliant idea.

A partnership in the 1970s between two biomechanical engineers—Bartel, a professor at Cornell University in upstate New York, and Albert Burstein, then director of the Department of Biomechanics at Hospital for Special Surgery in New York City—would change knee replacement surgery across the world, enable medical breakthroughs in nanobiotechnology and tissue engineering, and leave a lasting legacy that is the Center for Advanced Materials and Engineering in Orthopaedics, also known as CAMEO.

At the time, Bartel and Burstein were among the few researchers applying engineering research principles to the human musculoskeletal system—a combination of orthopaedics, biomechanical engineering, and expertise from surgeons that they would formalize into a program in 1978. Working with orthopaedic surgeon John Insall, one of their early innovations was a patented knee replacement—a posterior stabilized knee. Today, about half of all knee replacement surgeries worldwide are posterior stabilized and rely on that original idea.

“There were some places around the country where engineers were working in hospitals, but many wanted to do their own thing and would hope physicians would just leave them alone,” said Bartel, the Willis H. Carrier Professor Emeritus. “But for us, this was a program where there was direct collaboration between the university engineers and the hospital engineers and surgeons from the very get-go. It was just wonderful.”

While other hospitals were throwing out faulty knee implants retrieved from surgeries, Hospital for Special Surgery began collecting them so that Bartel and his colleagues could apply engineering analysis. They became one of the first labs to discover why plastic parts from the implants were wearing out, generating particles that would induce a harmful immune response in patients. The findings would change requirements for joint replacements from the FDA and become one of the highest cited orthopaedic journal papers of all time, according to Timothy Wright, who worked on the project under the guidance of Burstein.

“Our program changed clinical practice. It's that simple,” said Wright, who is now the F.M. Kirby Chair of Orthopaedic Biomechanics at Hospital for Special Surgery and co-executive director of CAMEO. “The biomechanics program was really driven by Don and his students. Don was our window to Cornell, and we were able to dangle these very interesting clinical problems in front of engineers up in Ithaca.”

The innovations didn’t stop there. For nearly 50 years, the program would continue to change medicine by bringing together the brightest minds in orthopaedics and engineering. The program eventually evolved into CAMEO and has grown its roster of official participants to about 50, including biologists, materials scientists, mechanical engineers, veterinarians, and surgeons.

A TEAM LIKE NO OTHER

As program researchers like Bartel, Burstein, and Wright developed better, more detailed engineering models of bones and implants, they started to have questions about the rules that govern how bone responds to load. How does mechanics affect the biology happening within bone as someone lifts a heavy box, for instance? They knew such research would require a more interdisciplinary approach, and so they began recruiting new engineers.

“The program was a huge part of why I decided to come to Cornell,” said Marjolein van der Meulen, the Swanson Professor and James M. and Marsha McCormick Director of the Meinig School of Biomedical Engineering. She was originally recruited to Cornell by Bartel, who often used the biomechanics program as a recruiting tool for faculty and students. Today, she is co-executive director of CAMEO.

Van der Meulen would eventually develop a bone loading model that simulates the stress on joints over time, highlighting not only cartilage degeneration and stiffening of bone, but also related changes adjacent to the joint. Developed in partnership with Wright and several other scientists from Hospital for Special Surgery, the popular model is now used by researchers across the globe.

Hospital for Special Surgery, considered the nation’s top orthopaedic hospital, sees 400,000 patients and performs almost 40,000 surgeries annually. For van der Meulen and many other engineers, having access to the resulting clinical data, bone samples, and surgeon expertise has been transformative.

“Hospital for Special Surgery is unique in that it has a strong population of surgeons who value research, and the institution has its own research division,” van der Meulen said. “Those interactions have been really important to our students’ and my success.”

CAMEO has served as fruitful training ground for students who eventually feed back into the university and hospital in the form of faculty and research appointments.

One of those students was Eve Donnelly, who spent time as a doctoral student in van der Meulen’s lab and as a postdoctoral associate at the Hospital for Special Surgery. Today, she’s an associate professor of materials science and engineering at Cornell, integrating materials science with translational orthopaedic research to better understand bone fractures. A project she led using bone samples from the hospital found that long-term use of bisphosphonates—a medicine taken by millions of osteoporosis patients annually to combat bone loss—can alter the composition of bone, making it more brittle and susceptible to a rare form of fracture in exceptional circumstances.

“Our partnerships with our clinician colleagues in the Metabolic Bone Disease and Orthopedic Trauma services at HSS and New York-Presbyterian Hospital were fundamental to the work,” said Donnelly. “Their clinical insights, as well as their large case volumes, uniquely enabled our findings to have the greatest translational impact.” 

MATCHMAKING

A new type of treatment for osteoarthritis, currently in canine clinical trials, shows promise for eventual use in humans thanks to another collaboration at CAMEO.

The treatment is a synthetic version of a naturally occurring joint lubricant that, once injected into a joint, binds to the surface of cartilage and acts as a cushion during high-impact activities, such as running.

The lubricant was developed by Lawrence Bonassar, in collaboration with David Putnam, Professor of Biomedical Engineering and Chemical and Biomolecular Engineering, and other biomedical engineers at Cornell along with Scott Rodeo, an orthopaedic surgeon and clinical scientist at Hospital for Special Surgery. Bonassar, the Daljit S. and Elaine Sarkaria Professor and CAMEO site co-director, has also worked with the hospital to research how hyaluronic acid injections provide pain relief to osteoarthritis patients, and has developed hyaluronic acid and collagen gels to treat herniated discs.

“If you have the right experimental and analytical framework, you can identify what qualities of these lubricants are the things that correlate to clinical success,” said Bonassar, who is also working with drug company Fidia Farmaceutici. “Working with Fidia enabled us to characterize one of the newest and most highly engineered hyaluronic acid products on the market, but also uncovered basic principles that underly the utility of all of the hyaluronic acid products in current clinical use. These partnerships started entirely because of a matchmaking event by Tim Wright.”

“Matchmaker” may not be in anyone’s official title, but coordinating interactions between the hospital and the Ithaca campus is an essential function of anyone in a leadership position at CAMEO.

When Karl Lewis, assistant professor of biomedical engineering, joined Cornell in 2020, he was quickly introduced by van der Meulen to Miguel Otero, an associate scientist in Hospital for Special Surgery’s Orthopedic Soft Tissue Research Program.

Lewis brings to Cornell expertise in multi-photon microscopy and other techniques for observing cell communication in living tissue, for example, using loading devices to study real-time dynamics in cell calcium signaling. In partnering with Otero, he gains access to surgical techniques, methods of analyzing cartilage, and potentially bone and tissue samples that can be used to study the correlations between cell signaling and disease.

“Studying the earliest stages of osteoarthritis where the cells have not yet affected the tissue, but their behavior has changed, that's something that intravital imaging with multi-photon microscopy is uniquely positioned to interrogate,” Lewis said. “That’s an area where Miguel and I could collaborate really well, with my lab developing an instrumental method and his lab providing cartilage biology expertise to explain what we're seeing. That could lead to some really big and impactful information about a disease that we still don't know a lot about.”

Another “matchmaker” is Suzanne Maher, associate director of the hospital’s Department of Biomechanics and CAMEO site co-director, who played a large role in helping to expand the biomechanics program into a center. With CAMEO’s growth has come more networking events such as annual research retreats, as well as travel accommodations, student training programs, and staff support.

“As problems were getting more multidisciplinary, we knew we needed to attract not just mechanical engineers, but materials scientists, tissue engineers, biological immunologists, and veterinary surgeons,” Maher said. “All of our fields are growing so quickly, and there's so much knowledge out there, but in some environments, people just don't have time to sit and talk. That's what we're trying to do with CAMEO, give people a chance to communicate, to brainstorm ideas, and to really see how we can be at the cutting edge of what's going on in orthopaedics.”

SHOW ME A KNEE

Ana Witkowski has dedicated the last three years of her life to researching musculoskeletal joints, but there’s one in particular she hopes to see for the first time this coming semester—a hip or knee on the operating table.

Witkowski is a doctoral student in van der Meulen’s research group, using bone loading models to study the role of parathyroid hormone treatment in osteoporosis and osteoarthritis. The treatment helps osteoporosis patients reduce bone loss by increasing bone formation. But Witkowski theorizes that the treatment can have unintended, yet beneficial, effects on cartilage as well. Her experiments show that the treatment’s ability to increase bone mass may attenuate the development of load-induced arthritic joint damage.

“My hope is we can affect the progression of osteoarthritis to the point where we don't just have to give out painkillers or totally replace the joint,” said Witkowski.

Analyzing bone samples in mice is one thing, but seeing osteoarthritis in humans and interacting with the clinicians who see those patients adds a new dimension to the research. That’s why Witkowski is excited to be working with CAMEO as a fellow in the center’s Combined Engineering and Orthopaedics Training Program enabled by a grant from the National Institutes of Health. All graduate students trained in the program have a team of mentors that includes a Cornell faculty member and a clinician at Hospital for Special Surgery, and each engineering student works on a collaborative project that includes a semester of research at the hospital’s main campus.

“I’m going to go look at how these treatments we've been analyzing in mice for years actually translate into patients, because parathyroid hormone has been attempted to be used as an osteoarthritis treatment, but it hasn’t been entirely clear if it works,” said Witkowski, who will be co-mentored by leading orthopaedic surgeon Mathias Bostrom, MD. “I’ll get to see if there are other factors at play and if it’s actually changing anything in the joint. I also hope to get access to data and even get some samples from knee replacement surgeries that I can look at.”

Another formal opportunity for biomedical engineering students to partner with Hospital for Special Surgery came this past academic year when the hospital sponsored three M.Eng. projects. The projects included sticky hydrogels for knee cartilage defects, tracking parental compliance for infant hip dysplasia treatment, and the “KneeTester,” a device for ACL injury diagnosis.

According to Wright, the design specification for each project changed drastically as the engineering students spent more time with clinicians and learned about challenges in applying the treatments.

“Experiences at the hospital have also been quite formative for the career trajectories of our engineering students,” van der Meulen said. “A lot of the students have wanted to pursue career settings where they're closer to the clinic after they've experienced the clinical environment at the hospital.”

For Witkowski, the CAMEO training program is exactly what she sought in becoming an engineering student—to apply her background in biomolecular science to directly solve a real-world problem.

During her upcoming semester at Hospital for Special Surgery, Witkowski hopes to find time in her busy schedule to observe at least one knee or hip replacement surgery from the operating room—a perspective she said would give her a deeper appreciation for the work she is doing.

“I'm excited to see if I can help discover something new that will benefit osteoarthritis and osteoporosis patients,” Witkowski said.

3D printers, quantum computers, and the future of orthopaedics

Writing in a 1992 edition of Cornell Engineering Quarterly, Bartel predicted that, thanks to collaborations between engineers and orthopaedic clinicians, “It should be possible, in the near future, to design artificial joints that will provide at least twenty years of pain-free function.”

That prediction has come to fruition, which begs the question: What do today’s engineers and clinicians think the future holds?

“Experts have said for a long time that metal implants are going to disappear, but I think that's always been a 50-year horizon, not a 20-year horizon,” said van der Meulen. “At the same time, every once in a while there are these giant leaps forward.”

One way metal implants could be replaced is with regenerative medicine. Therapeutic stem cells, tissue engineering and the production of artificial organs are all research areas being pursued at Cornell. An example is the bioprinting being pioneered in Bonassar’s lab.

“Additive manufacturing, 3D printing, or other current manufacturing methods could enable the production of engineered implants,” said Bonassar, who co-founded a company that announced a first-of-its-kind clinical trial in June in which a human received a 3D-bioprinted ear implant grown from the patient’s own living cells. “Hard implants, soft, synthetic, living, all of the above, could be capable of doing things in the future that we can't imagine.”

Like many other CAMEO researchers, Maher predicts machine learning and computer science will play a momentous role in orthopaedics and medicine in general. The emerging research area in the field of orthopaedics will bring “individuality” to patient care, said Maher, and help clinicians recognize patient-to-patient differences in anatomy, mechanics, and biology.

“One area is the development of tools to give surgeons real-time data in the operating room about how their surgical techniques are affecting joint mechanics,” said Maher, who expects Cornell’s renowned expertise in computer science to eventually assimilate into CAMEO. “This approach provides unparalleled opportunities to optimize surgery with immediate feedback.”

Another emerging focus is developing patient-specific imaging-derived models—built from MRI scans, for example—so that surgeons can model their planned surgeries and any possible deviations to study their mechanical effects ahead of time.

“The dream is to merge these models with biological data so that we can eventually feed to multi-faceted per-patient data into algorithms, which can help to direct patient care and optimize outcomes,” said Maher. 

Whatever the future holds, CAMEO is uniquely poised to play a leading role.

“Answering the most challenging questions in orthopaedics requires bringing together multidisciplinary teams of brilliant researchers and extraordinarily talented clinicians, and that’s what we’re doing at CAMEO,” Maher said. “Ultimately, we’re enhancing the health and wellbeing of our patients, and changing lives for the better.”