The engineer Georg Duda is interested in tissue regeneration – a term used by physicians to describe the body’s ability to completely restore tissue and its function following injury or illness. This often results in scarring due to changes to the tissue, but not always. “Bone is a prime example of scar-free regeneration,” Duda says. “After a fracture, a bone usually heals without scarring, fully restoring form and function.” Both scar formation and complete regeneration rely on cellular self-organization, which involves cells pulling together the wound edges and producing fibronectin and collagen to close the wound. Subsequently, blood vessels grow into this structure and in further steps the bone is remineralized.
Interplay between mechanical stress and inflammation
Duda and his team were able to show that, directly after a fracture or injury, the healing success depends on both mechanical influences and successive inflammatory responses. The formation of new blood vessels, a process known as angiogenesis, is also dependent on these influences. The fact that bones normally heal without scarring, while muscles, tendons, and ligaments are prone to develop scars is partly due to the relationship between two immune cell types: A larger number of CD4-positive T cells but a small number of CD8-positive T cells are present in bone after a fracture. “This ratio ensures slow but perfect healing of bone fractures,” Duda explains. “But in tendons, for instance, it’s exactly the opposite: Here, the CD8-positive T cells often predominate after a rupture, and the tendon never heals perfectly.” The biomechanics expert is convinced that it is important to carefully damp down inflammation and initiate the regeneration phase early on after injury.
“Our goal is to lay the groundwork so that patients experience less scarring,” Duda says. “We want to achieve this by bringing together two previously separate worlds: immunology and mechanics.” The scientists would particularly like to study the inflammatory response in the area of injury and the mechanobiology of regeneration. “We are thus establishing,” Duda adds, “the new field of immunomechanics.”
Combining immunology and mechanics
“We want to find out how immunology and mechanics are interrelated,” Duda says, describing the project that the ERC grant will now make possible. First, the team plans to investigate the different mechanical conditions that immune cells encounter during the early stages of healing or non-healing. Under different mechanical conditions, they plan to study the interactions of immune cells with connective tissue cells and fibroblasts in artificially created “niches.” They hope that by altering conditions they will be able to facilitate better healing, and in the ideal case scar-free healing. Finally, they want to test their hypothesis that these synthetic niches alter the composition of the early healing phase, thereby reducing scarring or eliminating it altogether.
Professor Christopher Baum, Scientific Director of the Berlin Institute of Health at Charité (BIH) and Chief Translational Research Officer of Charité – Universitätsmedizin Berlin, congratulates Georg Duda on the receipt of this prestigious grant: “As a trained engineer, Georg Duda is living proof of the value of interdisciplinary work. His biomechanical expertise and ideas for medicine have inspired the entire BIH Section ‘Advanced and Personalized Therapies,’ of which he is the spokesperson. Here, representatives from various fields of basic research and clinical science come together and collaborate: immunologists work with orthopedists, surgeons with materials scientists. The Institute is thus ideally equipped for this important ERC project. Translation can succeed here, and hopefully many patients will soon benefit from the research findings.”