Spatial immobilization of endogenous growth factors to control vascularization in bone tissue engineering
The intimate crosstalk, between endothelial and bone cells is essential for the reconstruction of bone defects. Indeed, a successful bone repair is greatly dependent on the formation of new blood vessels, to ensure the supply of nutrients and excretion of metabolites. Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) are involved on cell differentiation and bone vascularization to develop viable bone tissue. Herein it is hypothesized that endogenous BMP-2 and VEGF bound in a parallel arrangement over a single nanofibrous substrate (NFM) can lead to a successful osteogenic and angiogenic differentiation of mesenchymal stem cells. An engineered biofunctional system was developed comprising anti-BMP-2 and anti-VEGF antibodies immobilized over the same NFMs in a parallel pattern design, in an attempt to recreate the vasculature of a bone tissue. The osteogenic and angiogenic potential of this engineered biofunctional system was demonstrated by culturing human bone marrow-derived mesenchymal stem cells (hBM-MSCs) during 21 days without exogenous induction. A chick chorioallantoic membrane (CAM) assay showed that the engineered biofunctional system comprising endogenous BMP-2 and VEGF bound induced an increased angiogenic response. The angiogenic ability of this system, together with the osteogenic inductor BMP-2 enable obtaining an effective vascularized bone tissue engineering approach.