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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Regeneration Support
Guiding local immune response in bone healing

The aim of the project is to design a biomaterial that can be introduced into the body minimally invasive and act as a local immune system manipulator, preventing a possible escalation of the inflammatory response during regeneration.

Smart biomaterials for local immune modulation to steer the intrinsic healing response in bone healing

A scanning electron microscopy image shows an antigen-releasing scaffold that can recruit antigen-specific T-cells to sites of ischemic injury. Credit: Wyss Institute at Harvard University

Up to 15% of the patients with a fracture suffer from a delayed and incomplete (non-union) healing outcome. The treatment can take several months, producing costs of €8,000 to €91,000 per case. Since the risk of non-union fracture peaks in early adulthood, most patients will lack at work and be impaired in daily life for months, leading to a high socioeconomic impact for them.

Besides the defense against bacteria and viruses, the immune system is performing vital functions in tissue homeostasis, disease processes, and regeneration. The importance of the immune system in regeneration is probably most prominently seen in Axolotls. Albeit they have the capability to regrow a whole limb, depleting macrophages prior to the amputation diminishes the enormous regenerative potential. Even for bone healing itself there is a tight spatial and functional connectivity between the immune system and bone tissue. Not only is the bone marrow the birth place of the immune cells, but bone and immune cells share also common progenitors. After a fracture, the healing cascade starts with an inflammatory response that later on is followed by an anti-inflammatory phase. A poor healing outcome is often associated with a delayed transition from the inflammatory to the anti-inflammatory/regenerative phase.

Therefore, the aim of the project is to design a biomaterial that can be introduced into the body minimally invasive and act as a local immune system manipulator, preventing a possible escalation of the inflammatory response during regeneration. In the future, we hope that the lessons learned from bone as a tissue model with a high intrinsic healing capacity may also be applied in other tissues with lower intrinsic healing capacities.