In the proposed study, we aim at paving the path for using the HIF-stabilizer Deferoxamine (DFO) for a new application to prevent fracture healing disorders as a cost-effective and low-risk alternative to recombinant growth factors such as BMP-2. We consider the
FDAshort forFood and Drug Administration approved DFO and commercially available as Desferal® (Novartis), listed on World Health Organization's List of Essential Medicines, suitable for rapid clinical translation to improve fracture healing and the treatment of bone healing disorders. In the next step, we strive for clinical translation.
The
BfRshort forGerman Federal Institute for Risk Assessment is participating in this study as one of two laboratories that will test varying concentrations of DFO regarding their influence on mesenchymal stromal cells (precursor cells for bone forming osteoblasts). Both laboratories will work with harmonized protocols and the same cell culture reagents and cells. Furthermore, both laboratories will receive blinded samples of DFO in different concentrations. The data from both laboratories will then be send to a third project partner for evaluation. This is meant to investigate how good the comparability of
in vitro studies from different laboratories actually is and if such study design has clear advantages. We also plan to investigate the effect of DFO in our bioreactor (bone-on-a-chip). In addition, the data from the
in vitro experiment is meant to be compared with data from animal experiments to evaluate how precise a carfully conducted
in vitro study can predict the outcome of
in vivo approaches. Data from the bone-on-a-chip experiments will also be compared to results from
in vitro cell culture and
in vivo experiments to classify their significance. These research questions have direct relevance for the work of Department 9 (Experimental Toxicology and ZEBET) in the field of the 3R (Reduce, Replace, Refine), since this study is meant to show that the number of animal experiments can be reduced by an improved study design and the use of reliable
in vitro