Smart cartilage drip feeds arthritis drugs into joints under stress
Although anti-inflammatory drugs can be used to tackle conditions like osteoarthritis, there are downsides to our current methods of delivery, including the need for regular injections or the fact that these medications affect the entire body. New research at the Washington University School of Medicine in St. Louis could address these shortcomings, through an engineered "smart cartilage" that secretes an anti-inflammatory drug when a joint is placed under mechanical stress.
The inflammation of the joints that occurs through degenerative conditions like osteoarthritis and autoimmune conditions like rheumatoid arthritis is painful, debilitating and difficult to treat. Drugs are available to temper the inflammation and swelling, making lives easier for sufferers, though there is plenty of room for improvement in how these medications are administered.
Anakinra, for example, is a drug used to treat rheumatoid arthritis, but users need to change the injection site each time that they use it, while it also brings a risk of infections such as pneumonia or allergic reactions. Through slow-release microcapsules and even hydrogels that can be injected and release the drugs in response to mechanical force, scientists are making promising inroads in this area, and this latest study shapes as another exciting step forward.
It bears some resemblance to aforementioned hydrogel, in that it is designed to only release the drugs when a joint is placed under mechanical stress, such as a bending of the knee. This is seen as a way of addressing the discomfort of osteoarthritis in particular, where pain can result from these types of regular movements, making daily life difficult.
The scientists started by studying cartilage cells taken from pigs, and were able to identify key pathways in these cells that respond to stress, along with gene circuits in the cartilage that are switched on in response to mechanical loading. They then turned to genetically engineering to create versions of these cells that don't just respond to stress by driving inflammation, but produce the drug anakinra as part of the process.
“We altered snippets of DNA in the cells to tell them to do something different than normal when they sense a load,” said senior investigator Farshid Guilak. “That is, to make an arthritis-fighting drug.”
These experiments were carried out in the lab where the scientists mimicked mechanical stress of the joint by compressing the cells with a a tiny glass pipette, causing them to release the anti-inflammatory drug in response. Delivering the drug in this way, where it could be drip fed into affected joints to counter inflammation as it arises, could make it much more effective, as Guilak explains.
“This drug doesn’t seem to work unless it’s delivered continuously for years, which may be why it hasn’t worked well in clinical trials involving patients with osteoarthritis,” he said. “In our experiments in cells in the lab, we used existing signaling systems in the cartilage cells that we engineered so that they would release the drug whenever it’s needed. Here, we are using synthetic biology to create an artificial cell type that we can program to respond to what we want it to respond to.
Aside from avoiding regular injections and improving the effectiveness of the drug, this method could also negate many of the side effects driven by long-term delivery, which include hair loss, fatigue and stomach pain. Promisingly, the team believes the technique could be applied elsewhere in medical science.
“We can create cells that automatically produce pain-relieving drugs, anti-inflammatory drugs or growth factors to make cartilage regenerate,” Guilak said. “We think this strategy could be a framework for doing what we might need to do to program cells to deliver therapies in response to a variety of medical problems.”
The research was published in the journal Science Advances.