Description of PhD project
It is well known that fracture healing is a highly orchestrated process going along with inflammation,
angiogenesis and tissue remodeling. This healing cascade is triggered by the appearance of different
cell types and the secretion of various cytokines and growth factors. Cells immigrating into the
injured area need to adapt fast to the altered environment and start proliferation and differentiation.
Thus they have a high energy demand. There is growing evidence that cells are sensitive to metabolic
reprogramming by nutrientsensitive modifications of transcriptional active proteins, such as
acetylation or glycosylation. These processes depend on the availability of metabolic pathway
intermediates. The linkage of metabolic and signaling pathways allows cells to modulate actions as
metabolism, proliferation and differentiation according to their metabolic resources. This highlights
the possibility that the energy metabolism driven by the accessible nutrients and the metabolic
microenvironment affects the phenotype of cells immigrating the injured bone and can influence
regeneration by affecting Macrophage phenotype, T cell polarization or stem cell differentiation.
Hypothesis: The appearance and function of distinct cells during bone repair are regulated by the
local metabolic environment.
In this project the local metabolic conditions will be analyzed by metabolomics and proteomics at
different stages during bone regeneration under normal and mechanical disturbed healing conditions
(rigid and semi-rigid fracture fixation) in young and aged animals. The obtained results will be
connected to the existence of different cell subsets (detection via e.g. flow cytometry,
immunohistochemistry), surrounding mechanical conditions, as wells as age.
The aim of this project is to understand the correlation of energy metabolism with the appearance
and function of cell subsets and subsequent healing outcome during bone fracture repair.