A twisted ankle, broken hip or torn knee cartilage are all common injuries that can have medical ramifications long after the initial incident that causes them. Associated pain, inflammation, joint degeneration and even osteoarthritis can sideline a variety of different people: athletes, weekend warriors and patients who are either aging or inactive.
A team from Washington University in St. Louis was awarded $1.7 million from the National Institutes of Health (NIH) to develop a new therapeutic treatment that can deliver disease-modifying compounds in a manner to delay the development of inflammation, joint degeneration and arthritis with all the associated discomfort, disability and pain.
“We’re starting to see that many areas can’t be reached via oral drug delivery,” said Lori Setton, the Lucy & Stanley Lopata Distinguished Professor of Biomedical Engineering at the School of Engineering & Applied Science. “For example, synovial joint fluid in the knee is almost optimized to rapidly clear compounds out of the joint. So we’re trying to trick the joint into being a good host for the therapeutic drugs we are delivering.”
Setton, whose lab focuses on the role of mechanical factors in the breakdown and repair of soft tissues, said an intracellular compound called nuclear factor kappa B (NF-kB) is a main culprit in cellular breakdown, inflammation and pain after an injury. She’s working in the lab on a new solution using silk to deliver two specific molecules that can inhibit NF-kB at the site of a fracture or injury in an effort to stave off long-term joint damage.
“Silk naturally doesn’t interact with water, and, when you mix it with these molecules that also don’t interact with water, they bind to each other very strongly,” Setton said. “We believe these selective compounds are therapeutically effective, but we’ve never been able to get them to their target site. By delivering them with the silk, we hope to get large doses to the target site with low toxicity and to have them remain in that compartment for longer periods of time.”
In preliminary work with Tufts University investigator David Kaplan, Setton showed that model compounds can reside in the joint space about five times longer if delivered with silk microparticles than if delivered alone. Silk is an attractive delivery vehicle because of its long history of safe clinical use, and Kaplan has received NIH support to promote translational uses of silk for medical and other applications. It was initial work in delivering silk to the knee joint that drove Setton to identify a suitable, disease-modifying compound for treatment of arthritis through collaborations with the Musculoskeletal Research Center at the Washington University School of Medicine.
Setton and her co-investigators at the School of Medicine — including Yousef Abu-Amer, professor of orthopaedic surgery; Farshid Guilak, professor of orthopaedic surgery; and Gabriel Mbalaviele, associate professor of medicine in the Division of Bone and Mineral Diseases — soon will start testing the new delivery system in animal models.
“Delivering drugs orally to combat NF-kB-mediated problems at specific locations in the body, such as the injured knee, can be associated with harmful biological functions,” Abu-Amer said. “So this type of site-targeted approach to inhibit elevated NF-kB is essential if we want to provide effective treatment to the targeted site.”
According to Setton, the enhanced drug-delivery system has the potential to prevent the onset and progression of joint damage in patients suffering from acute injuries, like minor joint fractures, ligament or meniscal tears.
“Patients with joint trauma tend to go on to develop osteoarthritis at a higher rate compared to someone who doesn’t have the injury,” Setton said. “It’s a whole different type of arthritis development that we don’t know a whole lot about, but we believe we can intervene early with new drug delivery and treatments, and prevent onset at a later stage.”...
Lori Setton, a renowned researcher into the role of the degeneration and repair of the body’s soft tissues, has been named the Lucy and Stanley Lopata Distinguished Professor of Biomedical Engineering at Washington University in St. Louis. She was installed Oct. 24 in a ceremony at Whitaker Hall.
Setton joined the School of Engineering & Applied Science faculty in 2015 from Duke University. Her research uses tools from mechanical engineering, materials synthesis and cell and molecular biology to advance use of drug depots, or those injected in a local mass from which it is gradually absorbed by surrounding tissue, and biomaterials as therapies for musculoskeletal diseases.
The professorship was established in 1996 through the generosity of the late Stanley and Lucy Lopata.
“Few names are as recognizable across the Danforth Campus as that of Stanley and Lucy Lopata,” said Chancellor Mark S. Wrighton. “For decades, they provided generously in support of faculty, students, and facilities at Washington University. I am so pleased that their names will now be associated with the important work of Professor Lori Setton.”
“Lori Setton is the perfect example of an engineer who can tackle a problem using tools from multiple disciplines of engineering,” said Aaron F. Bobick, dean of the School of Engineering & Applied Science and the James M. McKelvey Professor. “She expertly blends her vast knowledge in mechanics, materials and cell biology to develop biomaterials that could be used in the treatment of painful musculoskeletal conditions, such as herniated disks or arthritis. We are grateful for the Lopatas’ generosity to Engineering at Washington University that continues their legacy.”...
Maybe it happened after you hauled a house’s worth of boxes to and from a moving van while helping a friend move. Maybe it startled you after a seemingly innocuous fender bender. Or maybe you noticed it after spending day in and day out — for years — hunched over your laptop keyboard.
Whatever the case, it is likely that you have experienced the agony of low-back pain. One study estimates that 80 percent of the U.S. population will experience a back problem at some point in their lives. And according to the 2010 Global Burden of Disease study, low-back pain is the top contributor to disability both in the United States and globally.
Lori Setton, PhD, the Lucy and Stanley Lopata Distinguished Professor of Biomedical Engineering, has made it part of her life’s mission to help solve this problem. Much of her research focuses on developing materials for soft-tissue regeneration, which could unlock a cure for many back problems. After a successful two-decade tenure at Duke University, Setton arrived at Washington University in summer 2015 to zero in on this issue. With the help of a new set of campus collaborators, her already remarkable work has risen to a new level....
Lori Setton, PhD, professor of biomedical engineering at Washington University in St. Louis, has been elected president of the Biomedical Engineering Society (BMES), a professional society for biomedical engineering and bioengineering.Setton, the Lucy and Stanley Lopata Distinguished Professor of Biomedical Engineering and professor of orthopaedic surgery at Washington University School of Medicine in St. Louis, joined the university in 2015 from Duke University, where she was the William Bevan Professor of Biomedical Engineering and Bass Fellow and associate professor of orthopaedic surgery.She is a fellow of BMES and of the American Institute of Biological and Medical Engineering and earned a Presidential Early Career Award from Scientists and Engineers (PECASE) in 1997, as well as several awards for excellence in mentoring....