Angiogenesis and Immunomechanics

Healing begins with the self-organisation of cells in the wound to reestablish structured tissue and restore the mechanical stability and intrinsic pretension of the injured matrix lost through the injury. Our aim is to decipher this independent organisation of fibroblasts, vascular precursors, immune cells and mechanical instability in the complex environment of the tissue. A better understanding of this interplay forms the basis for novel therapeutic approaches in musculoskeletal regeneration.

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Fracture Healing and Metabolism

Within this project we aim to identify the impact local metabolic changes may have on regenerative cascades using bone repair as a model system. To this end, we perform comparative metabolic analyses in normal and compromised fracture healing.

Zusammenspiel von Stoffwechsel und Frakturheilung

Schematic overview of the different bone healing phases and the molecular processes present at the respective timepoints. From: Loeffler, J. et al. Trends Endocrinol Metab 2018; 29(2):99-110.

Bone healing is a well-orchestrated interplay of cellular and molecular processes. However, the cells involved face a variety of challenging situations in regards to oxygen, nutrient and energy supply. In fact, there is growing evidence that immune cells, mesenchymal stromal cells and other progenitor cells are sensitive to metabolic reprogramming and that the cells’ metabolic requirements affect additional cellular functions beyond the request for energy provision. While much research has focused on the impact of cellular metabolism on basic immune cell function or stem cell differentiation, it is widely unknown how local energetic changes or imbalances (e.g. patient comorbidities such as diabetes, inflammatory diseases or advanced age) and related cellular metabolic reprogramming affect cell signaling and function during tissue/bone regeneration. In this project, we investigate how the metabolic micro-milieu and alterations contribute to fracture healing and the how this is connected to development of bone non-union in compromised healing conditions. As a long-term goal, we want to use and apply the knowledge gained to develop new therapeutic concepts for the treatment of impaired bone healing.

In Collabotation with

Dr. Stefan Kempa

Group Leader at the MDC

Publications