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In its study, the team found that AFM could pick up cartilage degradation in healthy mice well before the tissue showed visual signs of aging, and even before an electron microscope–a high-resolution imaging system that doesn’t measure mechanical properties–picked up changes. The team also detected damage in the cartilage of mice with a disease similar to human osteoarthritis when the mice were just one month old–well before the animals showed signs of the illness.

When the researchers used AFM on human-cartilage biopsies taken from patients undergoing knee or hip replacements, they found that it could pinpoint age-dependent breakdown in tissue–even in outwardly perfect cartilage–long before other instruments could. “We’re providing a nanoscale measurement that shows the breakdown of [molecules],” says Stolz. “You cannot detect that by any other means.” It’s possible that the technique could eventually be used to provide minimally invasive, early diagnosis of osteoarthritis. “By the time a patient comes in and complains, it’s too late. The cartilage has gone to pot,” says Reddi.

Even if clinical trials show the value of AFM for diagnosing the disease, Stolz acknowledges, there’s still no cure. However, AFM could help speed the development of osteoarthritis therapies. “If you produce a potential drug, you have to wait six months before you see its effect on the macro scale” using x-ray imaging or an arthroscope, says Stolz. “Our tool clearly showed the changes at one month … If you think about it in the development of drugs, it saves a lot of time and money.” Jingsong Wang, a rheumatologist at the University of Pennsylvania School of Medicine, agrees that the technology’s greatest benefit will be in drug development, noting that nine major osteoarthritis drugs failed in clinical trials due to the fact that patients did not show progress. “You have to show the progression in your treated group using an imaging tool, and the only approved tool is x-ray,” says Wang. “A [more] accurate measuring tool is a first step to studying this.”

The researchers hope to develop an arthroscope that integrates an AFM tip, enabling doctors to more accurately monitor the progression of osteoarthritis, and offering a better tool for assessing the effectiveness of osteoarthritis therapies currently under development. Stolz also plans to use the microscope on blood vessels in the heart and the brain to determine if AFM could detect early signs of risk of heart attack or stroke.

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Credit: Martin Stolz

Tagged: Biomedicine, diagnostics, drug development, molecular biology, molecular imaging, AFM, arthritis, biomechanics

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