New hope for osteoarthritis patients

| Hans Wolkers

Marcel Karperien, professor at the department of Developmental Bioengineering, developed an injectable hydrogel to repair damaged cartilage and potentially prevent the onset of osteoarthritis. Together with his colleagues from TechMed Centre, UMC Utrecht and Hy2Care, he optimized the gel to make it suitable for use in humans.

Osteoarthritis is a painful, inflammatory disease in the joints, that deteriorates the cartilage. Over time, this will result in a reduced function of the joint and even disability. Around two million people suffer from this disease in the Netherlands alone. In extreme cases, the diseased joint can sometimes be replaced by a prosthesis, to regain function. However, most people will have to live with the discomfort and pain.

Although the cause of the disease is mostly unknown, about 10-15 percent of all osteoarthritis develops when the cartilage has been damaged due to an accident. ‘A tackle in football, a fall while cycling or simply slipping: any person can easily damage the cartilage,’ says Leo Smit, CEO of company Hy2Care. ‘This may result in pain or stiffness, and eventually can lead to osteoarthritis.’

According to Marcel Karperien, there are currently no cartilage repair treatments that last. But this may change thanks to a new cure. Using a hydrogel developed at the UT that enables the body to heal cartilage itself, thereby preventing the possible development of osteoarthritis. This may be the solution for people with damaged cartilage due to an accident. The gel is in the first stage of testing on humans.

Dead cows

The development of a self-healing gel to repair damaged cartilage started as an idea to use a fluid filler, containing living cells, that could be injected into the affected joint. ‘Typically, it is quite difficult to work with living cells, so together with chemists, we focused on developing a gel, based on water and polysaccharides, long sugar-like molecules, that naturally occur in body tissues, including cartilage,’ Karperien explains.

‘After more studies, the scientists developed a liquid gel which became more solid because of the action of an enzyme, that stimulated the cross-linking of the polysaccharide molecules. When we injected the liquid gel in the knees of dead cows, we saw that it was binding to the extracellular matrix, and became firm.’ This extracellular matrix is a network of proteins and polysaccharides that supports the embedded cells. When injecting the gel in living animals, the scientists also observed that cells from healthy cartilage spontaneously migrated into the gel and started to grow. Karperien: ‘At this point, we knew that adding cells to the gel was not needed and that we could have an effective repair fluid for cartilage, based on just a gel.’ The next challenge was to make the gel suitable for use in living animals and eventually for humans.  

Impressive healing

Together with scientists of the Faculty of Veterinary Medicine in Utrecht, Karperien and his colleagues tested the healing properties of their new gel in knees of horses. These animals suffer from cartilage damage and consequently develop post-traumatic osteoarthritis quite frequently. This typically means the sick animal has to be euthanized. The research showed that, after the gel was injected in the affected knee joint, the damaged cartilage showed an impressive healing. After this proven success, it was time to develop the gel further for use in humans.

‘To bring the gel to the market as an effective product to treat cartilage damage in humans, we started the spin-of company Hy2Care,’ Karperien says. ‘They further developed the concept in their laboratories in Geleen, performed all safety tests and implemented strict medical regulations. They continue to make the product market ready.’ There were quite a few investors and one of the big drivers was ‘ReumaNederland’, the Dutch Arthritis Society.

After some years of research and perfecting the manufacturing process, the gel was ready to be tested on humans. ‘The final gel has eventually developed into a clinical kit existing of two components where one component is the polysaccharide fluid, and the other one is the cross-linking enzyme,’ Karperien explains. ‘It acts similarly to the well-known two-component glue.’ By injecting the two components separately into the joint, the enzyme and the polysaccharides are mixed, resulting in cross-linking and the formation of a firm gel. Cross-links are also formed between the gel and the healthy surrounding cartilage, making it a cohesive assembly.

Currently, the gel is clinically tested on 10 patients at UMC Utrecht, to guarantee its safety and effectiveness in humans. After this first clinical trial, the gel will be further evaluated in a larger patient group. Thereafter, it can eventually be certified as an approved treatment, although it may take a few more years before the treatment is widely available to patients.

Different applications

In collaboration with the Hy2Care team in Geleen, Twente is investigating a wider set of applications. For example, by further developing the gel, Karperien hopes to use it in other joints than the knees. ‘We are also looking for completely different applications, like for example, using the gel as a drug depot,’ he explains. ‘By injecting the gel that contains medication in a sick joint, a slow release may help to keep the joint healthy over longer periods of time.’

After many years of research, there is perspective for curing a painful disease. The new hydrogel offers hope for patients with damaged cartilage due to an accident, thereby potentially preventing the development of osteoarthritis. And maybe in the future, adaptations of the treatment can also be used to treat the large group of osteoarthritic patients where the cause of the disease is unknown.