Bone regeneration is seen as a model template for scarless healing. A new Collaborative Research Centre (SFB), entitled ‘Directed Cellular Self-Organisation for Advancing Bone Regeneration’ and led by Charité – Universitätsmedizin Berlin, will study which factors and mechanisms are important to allow a scarless regeneration and how they change as we age. It is hoped the findings will help us to understand the precise processes involved in bone regeneration and enable these processes to continue into old age. The underlying principles may serve as blueprint for regeneration also in other, even more challenging, clinical settings. Funded by the German Research Foundation (DFG), this collaborative research project will receive an initial grant of more than €12 million over four years.
Bone is one of the few tissues with the capacity for scar-free healing, meaning it is capable of complete regeneration of both structure and function. This makes bone an ideal model for understanding the general principles involved in cellular self-organization and the body’s ability to heal itself. While these healing processes generally work well in young and healthy individuals, they become impaired in older people and those with pre-existing conditions. Increasing age, lack of physical exercise, chronic inflammation and metabolic disorders all lead to changes in bone healing, which is why musculoskeletal disorders are more commonly found in older people. However, while regenerative potential can vary greatly between patients, standard care is so far remarkably uniform. A deeper understanding of how the body’s regenerative potential changes in response to age, metabolic disorders or an altered immune response (known as immunoaging) remains largely elusive. A greater understanding of these issues, however, is crucial for a personalized approach to treatment.
“The beginning of the healing process is crucial for long-term success”, explains SFB Spokesperson Prof. Dr. Georg N. Duda, who is also Director of Charité’s Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration and BIH Chair for Engineering Regenerative Therapies. He adds: “If the healing process is derailed early on, this will result in its delay or even failure. Key components of successful healing are a well-controlled immune response, adequate quantities of all supplies needed, and the structural integrity of the surrounding tissue.” Until now, these three aspects – inflammation, metabolism and mechanics – had only been studied in isolation. The aim of new SFB 1444 ‘Directed Cellular Self-Organisation for Advancing Bone Regeneration’ is to help improve our understanding of the relevant mechanisms and the coordinated manner of their interactions. Using bone regeneration as an example, the SFB’s researchers will undertake a detailed study of the fundamental mechanisms which determine whether the physical healing process ends in success or failure. The researchers hope to decipher how relevant interactions are controlled and regulated and how these might adapt throughout the normal aging process to ensure the body retains its ability to regenerate into old age.
This large collaborative project brings together leading experts in basic and clinical research from Charité, the Berlin Institute of Health (BIH), the Max Delbrück Center for Molecular Medicine (MDC), Freie Universität Berlin, the Zuse Institute Berlin (ZIB), the Max Planck Institute of Colloids and Interfaces and the German Institute of Human Nutrition in Potsdam. The collaboration comprises 28 researchers working across 16 projects. The project will be launched on 1 January 2021. In his role of Spokesperson, Prof. Duda is supported by Deputy Spokesperson Prof. Dr. Hans-Dieter Volk, who is Director of the Institute of Medical Immunology and Spokesperson of the BIH Center for Regenerative Therapies (BCRT).
“Our long-term goal is to influence the interactions between inflammation, metabolism and mechanics in a way that will enable physical regeneration even under challenging conditions,” says SFB Research Coordinator PD Dr. Katharina Schmidt-Bleek. It is hoped this will create the conditions needed for improved risk assessments and personalized treatment approaches.