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Winkler, Sophie; Mutschall, Hilkea; Biggemann, Jonas; Fey, Tobias; Greil, Peter; Koerner, Carolin; Weisbach, Volker; Meyer-Lindenberg, Andrea; Arkudas, Andreas; Horch, Raymund E. and Steiner, Dominik (2020): Human Umbilical Vein Endothelial Cell Support Bone Formation of Adipose-Derived Stem Cell-Loaded and 3D-Printed Osteogenic Matrices in the Arteriovenous Loop Model. In: Tissue Engineering Part A, Vol. 27: pp. 413-423

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Introduction:For the regeneration of large volume tissue defects, the interaction between angiogenesis and osteogenesis is a crucial prerequisite. The surgically induced angiogenesis by means of an arteriovenous loop (AVL), is a powerful methodology to enhance vascularization of osteogenic matrices. Moreover, the AVL increases oxygen and nutrition supply, thereby supporting cell survival as well as tissue formation. Adipose-derived stem cells (ADSCs) are interesting cell sources because of their simple isolation, expansion, and their osteogenic potential. This study targets to investigate the coimplantation of human ADSCs after osteogenic differentiation and human umbilical vein endothelial cells (HUVECs), embedded in a vascularized osteogenic matrix of hydroxyapatite (HAp) ceramic for bone tissue engineering. Materials and Methods:An osteogenic matrix consisting of HAp granules and fibrin has been vascularized by means of an AVL. Trials in experimental groups of four settings were performed. Control experiments without any cells (A) and three cell-loaded groups using HUVECs (B), ADSCs (C), as well as the combination of ADSCs and HUVECs (D) were performed. The scaffolds were implanted in a porous titanium chamber, fixed subcutaneously in the hind leg of immunodeficient Rowett Nude rats and explanted after 6 weeks. Results:In all groups, the osteogenic matrix was strongly vascularized. Moreover, remodeling processes and bone formation in the cell-containing groups with more bone in the coimplantation group were proved successful. Conclusion:Vascularization and bone formation of osteogenic matrices consisting of ADSCs and HUVECs in the rat AVL model could be demonstrated successfully for the first time. Hence, the coimplantation of differentiated ADSCs with HUVECs may therefore be considered as a promising approach for bone tissue engineering. Impact statement Due to their low donor-site morbidity, osteogenic potential and their good cell expansion, human adipose-derived stem cell is an interesting cell source. The goal of this study is to transfer thein vitroresults of increasing osteogenic potential upon cocultivation with human umbilical vein endothelial cell, to the rat arteriovenous loop model within the next step. Without using growth factors, the biomaterials, fibrin and HAp, which have already been successfully applied in clinical practice, are supposed to support bone formation by the implanted cells. The results demonstrated that vascularized bone tissue was formed in the cell-containing groups after 6 weeks.

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