Research Unit "Regeneration in Aged Individuals"

The relevance of mechanical boundary conditions as driving factor in bone regeneration and adaptation is generally well accepted. In addition, functional angiogenesis and vascular supply of a fracture zone are also considered to be key factors in healing and in the viability of regenerated tissues. However, the relationship and interdependence between tissue mechanical conditions and angiogenesis is not yet well understood.

Excessive amounts of senescent cells are associated with aging, impaired tissue repair and deterioration of organ function. However, senescent cells also promote health span since they prevent malignant transformation and support regeneration by modulating inflammatory responses.

Already in the very early phase of bone fracture healing, a complex extracellular matrix (ECM) network is assembled. The biochemical and mechanical signals provided by the ECM are believed to instruct cell fate and function.

Angiogenesis plays an essential role in bone healing and it is believed that morphogen gradients are the driving factors which orchestrate this process. However, it is largely unknown how the direct mechanical interaction of endothelial cells with stromal cells and cell-secreted ECM assists sprouting angiogenesis.

Immune cells are essential for the onset of regeneration and for the successful completion of the process. A balanced adaptive immune response is a deciding factor in the regenerative cascade and immune modulatory strategies represent a new therapeutic approach to enhance healing. Even though the osteo-immunological research has progressed remarkably, the adaptive immunity is often not considered.

Adipocyte-enriched yellow bone marrow develops during aging and obesity, among other metabolic disorders. It is thought to contribute to dysfunctional bone homeostasis and attenuated bone tissue repair. At the same time, aging and obesity are accompanied by a low-grade systemic inflammation (‘Inflamm-Aging’) and release of cytokines by local adipocytic cells. Together, these two factors are well-known negative regulators of bone healing.

Fracture healing is initiated with an inflammatory phase, during which immune cells invade the damaged tissue area. It is followed by a phase of bone repair. Both processes involve highly dynamic processes on the cellular and subcellular level, such as immune cell migration and cellular interactions between immune and stromal compartments. Intravital microscopy is the method of choice to study these processes.