Cartilage is hardly able to heal itself, and current therapeutic treatments leave much to be desired, which is why researchers are working on biomimetic and personalized solutions.
Painful joints, swelling and limited mobility: some five million Germans are currently suffering from osteoarthritis, which is the world’s most common joint disease. In medical terms, osteoarthritis means that wear and tear on the cartilage layer of the joints is greater than what would normally be expected given the patient’s age and could even be caused by an accident or fall.
"The forces acting between the bones are enormous. Healthy joint cartilage acts as a protective layer as well as a shock absorber, which enables the bones to glide across each other," explains Prof. Günter Tovar, who heads up the University of Stuttgart's Institute of Interfacial Process Engineering and Plasma Technology (IGVP), where researchers are collaborating with the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB to explore ways of repairing damaged cartilage.
By itself, cartilage only has a very limited ability to regenerate naturally due to the lack of blood supply and the small number of cells it contains. As Tovar explains, current treatments are not wholly adequate due to the fact there are different types of cartilage with different structures: we have hyaline cartilage, which acts as a shock absorber between bones, elastic cartilage in the auricle (outer ear), and fibrocartilage, which serves as an anchor point for tendons and ligaments.
The challenges associated with modern treatments
The fact that there are three subtypes of cartilage makes therapeutic interventions much more difficult. When treating joint cartilage damage, for example, surgeons deliberately damage the bone to cause a blood clot to form that contains stem cells, from which new cartilage cells can form.But what the body makes is fibrocartilage, which, by its very nature, is not designed to withstand the same compressive stresses as articular cartilage.
Another procedure involves taking articular cartilage from another part of the body and using it to construct new cartilage. Although these pieces of cartilage have near-optimal mechanical properties, they form a cartilage mosaic because they are the product of an injury to another part of the body. A different method involves extracting cartilage cells from the patient, cultivating them in vitro, multiplying them, and reinserting them after a few weeks, but this requires two operations, and it is not easy to create the right kind of cartilage.
Given these difficulties, the team at the IGVP is initially focusing on the internal structure of cartilaginous tissue. Articular cartilage consists of a macromolecular extracellular matrix whose key components are water and collagen, and is based around a triple helix, a structure that gives it high tensile strength and has virtually no elastic properties. The research team is using medical gelatin, which consists of fragments of collagen, to rebuild this triple helix structure. "What we're doing," Tovar explains, "is to give the cartilage cells the appropriate biochemical signals to make sure that they continue to differentiate and form the correct cell types giving us the basic frame, as it were, for intact articular cartilage tissue." The scientists make building blocks at the molecular level, which behave in as biomimetic a way as possible. "As long as the cells feel comfortable in the artificially engineered tissue, they can do their job and facilitate the regeneration of cartilage."
Healthy cartilage in joints serves as a protective layer as well as a shock absorber, which enables the bones to glide across each other.
Prof. Günther Tovar
The researchers also want to make the soft cartilage structures compatible with other processing technologies to which end they apply a chemical treatment to the gelatin to make its consistency suitable for use in, for example, 3-D printer additive manufacturing. The researchers then work in interdisciplinary teams to complete the subsequent processing steps. "We rely on interdisciplinary team play," says Tovar, "especially when it comes to interfacial engineering."
Focus on tissue regeneration
TriAnkle is an EU project that goes one step closer to practical application. "The objective of all of this," explains Pinar Koca, a doctoral student at the IGVP who is contributing to the project by researching cartilage regeneration, "is to develop clinically useful and personalized biological scaffolds for tissue regeneration in weight-bearing joints." This research consortium is composed of twelve partners in five European countries and includes organizations such as the Sports Clinic and the FC Barcelona Foundation. "Professional athletes and the clubs they play for," says Koca, "have a particularly strong interest in healing cartilage injuries rapidly and lastingly, which is why we are pleased to be able to contribute to the project by bringing in our findings from application-oriented basic research."
Author: Bettina Wind
Prof. Günter Tovar, Email, Phone +49 711 685 62304