title: Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels.
abstract: A major challenge in the development of clinically relevant 3D tissue constructs is the formation of vascular networks for oxygenation, nutrient supply, and waste removal. To this end, this study implements a multimodal approach for the promotion of vessel-like structures formation in stiff fibrin hydrogels. Computational simulations have been performed to identify the easiest microchanneled configuration assuring normoxic conditions throughout thick cylindrical hydrogels (8 mm height, 6 mm ∅), showing that in our configuration a minimum of three microchannels (600 μm ∅), placed in a non-planar disposition, is required. Using small hydrogel bricks with oxygen distribution equal to the microchanneled configuration, this study demonstrates that among different culture conditions, co-culture of mesenchymal and endothelial cells supplemented with ANG-1 and VEGF leads to the most developed vascular network. Microchanneled hydrogels have been then cultured in the same conditions both statically and in a bioreactor for 7 d. Unexpectedly, the combination between shear forces and normoxic conditions is unable to promote microvascular networks formation in three-channeled hydrogels. Differently, application of either shear forces or normoxic conditions alone results in microvessels outgrowth. These results suggest that to induce angiogenesis in engineered constructs, complex interactions between several biochemical and biophysical parameters have to be modulated.
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Arrigoni
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Bongio
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Talò
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Bersini
authors.affiliation: Faculty of Engineering, Division of Materials Science and Chemical Engineering, University of Yokohama, 79-1 Tokiwadai, Hodogaya-ku, Yokohama, 240-8501, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Enomoto
authors.affiliation: Faculty of Engineering, Division of Materials Science and Chemical Engineering, University of Yokohama, 79-1 Tokiwadai, Hodogaya-ku, Yokohama, 240-8501, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Fukuda
authors.affiliation: Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Via R. Galeazzi 4, 20161, Milan, Italy.|Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale (EOC), Lugano, 6900, Switzerland.|Swiss Institute of Regenerative Medicine (SIRM), Lugano, 6900, Switzerland.|Fondazione Cardiocentro Ticino, Lugano, 6900, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Moretti
mesh_terms: D042683:Angiopoietin-1 / Q000737:chemistry / Q000494:pharmacology; D002461:Cell Line, Transformed; D003198:Computer Simulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D055806:Microvessels; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D020100:Hydrogels; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: bioreactors; co-cultures; computational simulations; tissue engineering; vascularization