In our aging society, treating joint problems is becoming increasingly important. To do this, the cartilage damage must become repairable. But so far it has proved impossible to recreate the complex internal structure of cartilage. Professor Jos Malda has now received an ERC Advanced grant of €2.5 million to crack this code.
Combining biology and technology
Throughout his career, Jos Malda has dealt with the interface between biology and technology. It took him from his studies in Bioprocess Engineering at Wageningen to the position of Professor of Biofabrication in Translational Regenerative Medicine at Utrecht. Here at the Utrecht Center for Regenerative Medicine, he has been focusing on cell and tissue printing and regeneration for years. Jos: “It started with cartilage, because it looked relatively simple, without blood vessels and nerves. But it turns out to be very complicated, because it has a special structure.’
Cartilage is a challenging tissue due to its arched structure
Cartilage contains few cells, but a lot of collagen in an arched structure.
These arches provide strength and can withstand a lot, like similar shapes in old bridges or Antoni Gaudi’s famous buildings.”
Professor Jos Malda
Because cartilage has few cells, repair through the body’s own processes is difficult, and the solution lies primarily in being able to remodel the cartilage arches. “There are ways to repair cartilage, but they leave the collagen in a random orientation. This does not take as long and ensures that there is always a seam with the healthy tissue.’
A major contribution to the understanding of cartilage
The €2.5 million that Jos Malda is now receiving from the European Research Council, the largest individual grant in Europe, is intended to find out once and for all how these cartilage arches arise and how we can recreate them for regenerative therapies. “The great thing about this ERC Advanced grant is that it gives a lot of freedom. We have a detailed plan, but if the results show that we need to adjust our approach, then we can,” says Jos.
Learning from models and animals
One of the first steps in the project will be to create an ‘organ-on-a-chip’ cartilage model. This is a small model in which the pieces of cartilage can be studied in great detail. Jos: “We can make very small adjustments to such a model, for example changing the mechanical loading or adding certain substances. How the tissue responds teaches us step by step what is important for cartilage development.’
Another important phase is at the Faculty of Veterinary Medicine of the University of Utrecht. “I have been collecting cartilage from joints of various mammals for over fifteen years,” explains Jos. “It started with horses and dogs, but after having the opportunity to examine an elephant that died in a zoo, I began to look more broadly. Now I have a wide selection in the drawer, from giraffes and kangaroos to orcas and sperm whales.”
Each animal is a puzzle piece
This collection of animals – all accidental deaths – is now proving to be a goldmine. “We can link the difference in cartilage to a different lifestyle. Animals that swim in water face a completely different load than animals that walk on land, and this is shown by the joints and cartilage. Marine mammals, for example, do not have these characteristic arches. This suggests that the forces that occur during walking may play a role in cartilage development. In this way we continue to confuse more towards the answer.’
The best conditions for arches
Jos combines all the knowledge gained from research on other mammals and models with his expertise in 3D bioprinting – printing living cells and tissues. “We can already do a lot with our bioprinters. But we will have to combine the technological side of printing arcs with biological signals to ensure that such printing is ultimately successful and integrates well with the rest of the cartilage.”
A vision of a flexible joint
The ultimate goal of this knowledge is to create better treatments for humans and animals. “If we can better regenerate the cartilage and have repairs properly integrated into the rest of the joint, joints will stay healthy longer,” concludes Jos. “A healthy musculoskeletal system is becoming increasingly important for healthy aging. Especially now that we are getting better at treating other conditions, such as heart disease and cancer, and older people are living longer.’
