Endothelialized tissue engineered 3D-construct for bone repair

One of the main problems arising when implanting a graft into a large bone gap is its insufficient vascularization in the central region. This results in impaired bone healing and often leads to necrosis in the graft. Vascularization and bone formation have been shown to be very closely connected. In order to better understand the relationship between blood vessels and bone formation, we have studied the interactions between mesenchymal stem cells (MSC) and endothelial cells (EC). Since the blood vessel network undergoes dramatic remodeling during wound healing, a process that is connected with different endothelial cell maturational stages (reflected i.e. by different cell surface markers), we have also investigated the effect of growth factor-stimulated EC on MSC differentiation into bone forming cells. In addition, since during bone healing, one of the first events is the formation of a blood clot at the site of injury, we have evaluated the potential of platelet-rich plasma (PRP) as an osteoinductive substance by assessing its action on MSC differentiation. Finally, we combined all components into one autologous construct and to in vitro evaluate its potential to serve as a possible bone graft that could overcome the in vivo problem of limited vascularization generally occurring in large bone defects.