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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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ECM and Mechanical Strain

The role of mechanical strain of extracellular matrix fibers in directing the healing process

Collagen scaffold seeded with human dermal fibroblasts. Red = Actin; Green = Fibronectin; White = Collagen (Second Harmonic Generation)

Cells are actively organizing their extracellular matrix (ECM). This active organization of ECM fibers suggest the important role of mechanical forces generated by the contractile cytoskeleton, which is transferred to the ECM through focal adhesion complexes. Among the ECM components, fibronectin and collagen play a very important role in development and healing process, which according to the previous research is highly mechano-regulated. We aim to gain a better insight into the mechanism of force transmission from the cells to ECM and the long range signals resulting in growth and remodeling in the healing process. Therefore, it is necessary to be able to probe the interaction between fibronectin and collagen and the strain dependency of their assembly and organization in regeneration. By seeding macroporous collagen scaffolds and producing 3D micro tissues that mimic the healing process in soft tissues and early stage of bone regeneration, we study the mechanism of load transfer from Fibronectin to collagen and the influence of tissue tension on cell function and ECM growth, using Fluorescent Resonance Energy Transfer (FRET).