A team of researchers at the University of Cambridge are reimagining the treatment of chronic diseases. Led by Professor Oren Scherman from the Yusuf Hamied Department of Chemistry, the team have pioneered a new, responsive biomaterial that mimics human tissue and can adapt to the body’s changing chemistry, with potential to be used as an effective therapy for long-term illnesses.

Biomaterials can fall into many categories, including ceramic, metal and polymer implants, and are becoming increasingly more advanced. Biomaterials are often used to replace parts of the body – commonly joints – or to restore cardiac function: for example, replacing heart valves and blood vessels in bypass surgeries.

Recently, there has been an increasing focus on the development of biomaterials across the scientific literature, with the University of Cambridge leading the way. For example, the Cambridge Centre for Medical Materials has developed engineered cardiac tissue scaffolds, offering new potential for regenerative repair of heart muscle. The work done by Scherman’s research group, however, could fuel a new future of drug delivery systems.

“The work done by Scherman’s research group, however, could fuel a new future of drug delivery systems”

The team has developed a biomaterial that can change its mechanical properties in response to pH changes within the body. This material consists of polymers – long repeating chains of molecules which are kinetically locked together. The material can be loaded with drugs specific to a certain chronic condition. When the pH of the environment changes, the ‘locking’ of the molecules responds. This means as the acidity increases, as occurs in times of inflammation, the material becomes jelly-like, triggering the release of the drugs which are contained within. The material also appears to be an excellent mimic of human tissue and has thus been dubbed ‘artificial cartilage’.

One area in which it shows great potential is in the treatment of certain types of arthritis. Arthritis affects 1 in 6 people in the UK, with symptoms including pain, fatigue and immobility. The key types of arthritis include osteoarthritis and rheumatoid arthritis (RA), an autoimmune disease often affecting younger people. RA results in inflammation, swelling and often the breakdown of cartilage and bone in the joints, as well as problems in other organs.

At the moment, the main treatment options for RA are disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs, which block the immune system’s attack of certain joints. However, these immunosuppressants are very powerful drugs, including some of the same agents used in cancer chemotherapy, and as such have many side effects. The painful symptoms of RA are managed by painkillers and anti-inflammatories which would be utilised in the artificial cartilage.

“These materials can ‘sense’ when something is wrong in the body and respond by delivering treatment right where it’s needed”

Artificial cartilage does not aim to have a curative effect for arthritic conditions, but instead offers many people suffering relief in a way that is highly responsive to their body’s own chemistry. “These materials can ‘sense’ when something is wrong in the body and respond by delivering treatment right where it’s needed. This could reduce the need for repeated doses of drugs, while improving patient quality of life,” hopes first author Stephen O’Neill.

So what’s next for artificial cartilage? So far, the pH-sensitive material has only been examined in laboratory tests outside of the body, by injecting fluorescent dyes into the material to mimic the drugs. The next step will be to test the biomaterial in living animals to confirm that the drug release mechanism is successful and improve safety, before running extensive clinical trials in humans.

As well as aiming to improve the lives of people with arthritis, O’Neill says, “It’s a highly flexible approach, so we could in theory incorporate both fast-acting and slow-acting drugs, and have a single treatment that lasts for days, weeks or even months.”

These properties mean the material could also be ideal for cancer treatment. Many tumours create an acidic environment, like the inflamed joints, due to abnormal glucose metabolism in the cancer cells. With possible utility for treating both cancer and arthritis, the team will hopefully make a large contribution to medical treatment using this new, regenerative biomaterial.

The Melville Laboratory research team are enthusiastic about its success and the use of other future responsive biomaterials in future with Scherman saying, “For a while now, we’ve been interested in using these materials in joints, since their properties can mimic those of cartilage. But to combine that with highly targeted drug delivery is a really exciting prospect.”