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In vivo evaluation of bioprinted prevascularized bone tissue
Authors:Patrick Rukavina  Fritz Koch  Maximilian Wehrle  Kevin Tröndle  G Björn Stark  Peter Koltay  Stefan Zimmermann  Roland Zengerle  Florian Lampert  Sandra Strassburg  Günter Finkenzeller  Filip Simunovic
Institution:1. Department of Plastic and Hand Surgery, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany;2. Laboratory for MEMS Applications, IMTEK-Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany;3. Laboratory for MEMS Applications, IMTEK-Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany

Hahn-Schickard, Freiburg, Germany

Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Freiburg, Germany;4. Laboratory for MEMS Applications, IMTEK-Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany

Hahn-Schickard, Freiburg, Germany

Abstract:Bioprinting can be considered as a progression of the classical tissue engineering approach, in which cells are randomly seeded into scaffolds. Bioprinting offers the advantage that cells can be placed with high spatial fidelity within three-dimensional tissue constructs. A decisive factor to be addressed for bioprinting approaches of artificial tissues is that almost all tissues of the human body depend on a functioning vascular system for the supply of oxygen and nutrients. In this study, we have generated cuboid prevascularized bone tissue constructs by bioprinting human adipose-derived mesenchymal stem cells (ASCs) and human umbilical vein endothelial cells (HUVECs) by extrusion-based bioprinting and drop-on-demand (DoD) bioprinting, respectively. The computer-generated print design could be verified in vitro after printing. After subcutaneous implantation of bioprinted constructs in immunodeficient mice, blood vessel formation with human microvessels of different calibers could be detected arising from bioprinted HUVECs and stabilization of human blood vessels by mouse pericytes was observed. In addition, bioprinted ASCs were able to synthesize a calcified bone matrix as an indicator of ectopic bone formation. These results indicate that the combined bioprinting of ASCs and HUVECs represents a promising strategy to produce prevascularized artificial bone tissue for prospective applications in the treatment of critical-sized bone defects.
Keywords:bioprinting  bone formation  endothelial cell  mesenchymal stem cell  vascularization
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