Vascularized bone tissue engineered system comprising autologous growth differentiation factors and mesenchymal stem cells

Reconstruction of large bone defects still remaining a major clinical orthopedic challenge, since repair of a bone defect is not only the process of new bone formation, but also the formation of new blood vessels - angiogenesis ^[1]. Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) are involved on cell differentiation and bone vascularization to construct viable osseous tissue ^{[2, 3]}. Therefore, herein is hypothesized that the synergistic effect of autologous BMP-2 and VEGF parallel bound over a single nanofibrous substrate (NFMs) can lead to a successful osteogenic and angiogenic differentiation of mesenchymal stem cells. To achieve such ambitious goal, an engineered system was developed comprising BMP-2 and VEGF antibodies immobilized over the same structure in side-by-side fashion, trying to recreate the vasculature of a bone tissue. Furthermore, immobilized antibodies were capable of selectively immobilize the respective growth factor from a biological fluid (i.e. platelet lysate). The osteogenic and angiogenic potential of this engineered biofunctionalized system was assessed by culturing human bone marrow mesenchymal stem cells (hBM-MSCs) during 21 days without exogenous induction. Bare NFMs cultured with hBM-MSCs under basal and standard osteogenic or angiogenic differentiation media were used as negative and positive controls, respectively. Biological data demonstrate that the engineered biofunctional NFM comprising BMP-2 is able to promote osteogenesis, whereas the VEGF is able to promote angiogenesis of hBM-MSCs. Moreover, the vascularized bone tissue engineered system proposed is able to promote spatial angiogenesis and osteogenesis of hBM-MSCs, targeting an effective vascularized bone tissue engineering approach.

^[1]S. Almubarak, et al., Bone, 2016;

^[2]D. Barati, et al., J Control Release 223, 2016;

^[3]M. Bouyer, et al., Biomaterials, 2016.