HIPPOX · The mechanobiology of hypoxia during bone regeneration

Bone regeneration is a challenging clinical problem. Each year, millions of patients worldwide experience bone fracture: one every two-to-three seconds. Over 10-15% of these fractures suffer from impaired healing. Especially the elderly population is disproportionately affected being associated with permanent impairment and increased mortality. Two critical events early in fracture repair determine the outcome of the healing process: lack of oxygen caused by blood vessel rupture and mechanical instability. Thus, the progenitor cells that will eventually form cartilage and bone to heal the fracture must simultaneously adapt to both hypoxic and mechanical microenvironments to ensure full tissue restoration. Cellular hypoxia-induced signaling and mechanotransduction are therefore critical to bone healing, but how crosstalk between these pathways impacts fracture repair is unknown. The project aims to define new cellular and molecular mechanisms that mediate crosstalk between hypoxia and mechanical signaling during fracture repair and target this crosstalk in an innovative regenerative therapy to accelerate fracture repair. Improvement in therapeutic strategies and rehabilitation will have a global impact and are already included in European health care efforts to ensure health throughout the life course, and to reduce hospitalization time and mortality in the (elderly) population. The project will be conducted in the McKay Research Laboratory, University of Pennsylvania, United States (PENN), the Department of Chemistry, Materials and Chemical Engineering “G. Natta”, Politecnico di Milano, Italy (POLIMI, secondment) and the Centre for Translational Bone, Joint and Soft Tissue Research, Technische Universität Dresden, Germany (TUD).