Biomaterials
not be gold (or silicone or graphene or any other novel tech material).
Innovators may be good generating hype around a shiny new gadget, but all too often medical devices get rolled out before anyone can say just what their application might be. By the same token, not all pioneering medical devices need to be complicated, state-of-the-art contraptions. In many cases, the principle of Occam’s razor holds true; simplicity and efficacy go hand in hand. One recent invention, the STEM-device developed by rheumatology experts Thomas G. Baboolal, Elena Jones and Dennis McGonagle at the Leeds Institute of Rheumatic and Musculoskeletal Medicine is a case in point. “We called it a synovial brush, or a toothbrush for the knee,” McGonagle says. This no-frills bit of kit is a prime example of purpose- built equipment, specifically designed to turn sound scientific theory into groundbreaking therapeutic reality. The handheld STEM-device might look like a toothbrush, but it’s what it does that matters. Baboolal, Jones and McGonagle’s STEM-device is the product of almost two decades of research into native osteoarthritic abnormal joint environment and the mesenchymal stem cells (MSCs) that reside in synovial fluid. “We first discovered synovial fluid resident stem cells in 2004,” McGonagle explains. “And then in 2008, we found that these cells were 100 times more numerous in the fluid in early osteoarthritis.” Appearing in joint cavities, synovial fluid primarily works to lubricate and nourish articular cartilage. But when Jones and McGonagle discovered increased numbers of MSCs in the osteoarthritic abnormal joint environment, they began asking serious questions about where these cells originate and what they might do. In 2016, with Baboolal and others, they published their early findings in the Annals of the Rheumatic Diseases. Using a dog model of joint distraction – a technique whereby metal pins are placed across the knee joint to encourage space between the bones – McGonagle et al. demonstrated that “when we took out these stem cells, tagged them, re-injected them into the joint and pulled the joint apart, there was increased adhesion of these stem cells to the injured superficial cartilage,” he explains. “When you correct the mechanical environment,” so their theory goes, “the earliest pathology in osteoarthritis starts in the superficial cartilage and in the knee”.
Conservation, preservation and restoration
According to McGonagle, to date there are no proven medical therapies for osteoarthritis. The only established treatment is joint replacement, which, though tried and tested in a limited number
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of joints, is far from ideal. “For me, it’s like this,” McGonagle continues, “100 years ago you had dentists and they pulled teeth, and you had orthopaedic surgeons and they replaced joints. Now in dentistry, the last thing you want to do is pull a tooth: it’s all about conservation, preservation and restoration. The same is true in orthopaedic surgery. We know so much now about the reparative environment of osteoarthritis, that we could be getting all these [patients] in their 40s and 50s and creating an environment to regenerate the joints and keep them going without getting to this end-stage disease.” It’s this vision that put McGonagle, Jones and Baboolal on a track to create the STEM-device. The team at Leeds are not the first to harness MSCs for osteoarthritis, but the brilliance of their approach lies in its sheer simplicity, economy and efficacy. “To repair cartilage”, McGonagle explains, “surgeons have used a number of methods with limited success, including bone microfracture, cartilage biopsy with digestion, and culture expansion with cell reintroduction in a scaffold”. In the latter procedure, stem cells derived from bone marrow and other sources are “expanded in an expensive facility for up to a month, and then injected back into the defect via a carrier,” says McGonagle. Using the STEM-device, however, this process might be radically simplified. In a recent
“One-hundred years ago you had dentists and they pulled teeth, and you had orthopaedic surgeons and they replaced joints. Now in dentistry, the last thing you want to do is pull a tooth: it’s all about conservation, preservation and restoration. The same is true in orthopaedic surgery.”
paper published by Dr Ala Altaie, a stem cell biologist working alongside the Leeds orthopaedic team, findings revealed that the synovial brush could release enough stem cells to make cartilage in the lab, without the need for culture expansion. The STEM-device is designed to be used in conjunction with nascent regenerative orthopaedic procedures, such as joint distractions and wedge osteotomies. “We’re trying to set the scene so that surgeons appreciate that joints can repair themselves when you correct the environment,” McGonagle says. “When the surgeons are in the joint repairing it, they’re doing it under arthroscopy and irrigation, so the joint is expanded, and they are actually washing out stem cells and growth
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