title: Multi-casting approach for vascular networks in cellularized hydrogels.
abstract: Vascularization is essential for living tissue and remains a major challenge in the field of tissue engineering. A lack of a perfusable channel network within a large and densely populated tissue engineered construct leads to necrotic core formation, preventing fabrication of functional tissues and organs. We report a new method for producing a hierarchical, three-dimensional (3D) and perfusable vasculature in a large, cellularized fibrin hydrogel. Bifurcating channels, varying in size from 1 mm to 200-250 µm, are formed using a novel process in which we convert a 3D printed thermoplastic material into a gelatin network template, by way of an intermediate alginate hydrogel. This enables a CAD-based model design, which is highly customizable, reproducible, and which can yield highly complex architectures, to be made into a removable material, which can be used in cellular environments. Our approach yields constructs with a uniform and high density of cells in the bulk, made from bioactive collagen and fibrin hydrogels. Using standard cell staining and immuno-histochemistry techniques, we showed good cell seeding and the presence of tight junctions between channel endothelial cells, and high cell viability and cell spreading in the bulk hydrogel.
authors.affiliation: Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, UK.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Justin
authors.affiliation: Division of Trauma and Orthopaedic Surgery, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Brooks
authors.affiliation: Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, UK am253@cam.ac.uk.
authors.forename: Athina E
authors.identifier: 0000-0002-2265-1256
authors.initials: AE
authors.lastname: Markaki
mesh_terms: D000464:Alginates / Q000737:chemistry*; D002470:Cell Survival; D005780:Gelatin / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid; D005780:Gelatin
keywords: hydrogel; three-dimensional printing; vascular networks; vascularization