title: Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis.
abstract: We report the fabrication of a scaffold (hereafter referred to as AngioChip) that supports the assembly of parenchymal cells on a mechanically tunable matrix surrounding a perfusable, branched, three-dimensional microchannel network coated with endothelial cells. The design of AngioChip decouples the material choices for the engineered vessel network and for cell seeding in the parenchyma, enabling extensive remodelling while maintaining an open-vessel lumen. The incorporation of nanopores and micro-holes in the vessel walls enhances permeability, and permits intercellular crosstalk and extravasation of monocytes and endothelial cells on biomolecular stimulation. We also show that vascularized hepatic tissues and cardiac tissues engineered by using AngioChips process clinically relevant drugs delivered through the vasculature, and that millimetre-thick cardiac tissues can be engineered in a scalable manner. Moreover, we demonstrate that AngioChip cardiac tissues implanted with direct surgical anastomosis to the femoral vessels of rat hindlimbs establish immediate blood perfusion.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Boyang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Miles
authors.initials: M
authors.lastname: Montgomery
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: M Dean
authors.initials: MD
authors.lastname: Chamberlain
authors.affiliation: McEwen Center for Regenerative Medicine, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Korolj
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Aric
authors.initials: A
authors.lastname: Pahnke
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Wells
authors.affiliation: The Toby Hull Cardiac Fibrillation Management Laboratory, Toronto General Hospital, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Massé
authors.affiliation: Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Lewis
authors.initials: L
authors.lastname: Reis
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Abdul
authors.initials: A
authors.lastname: Momen
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.|Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.|The Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Nunes
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.|Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Wheeler
authors.affiliation: The Toby Hull Cardiac Fibrillation Management Laboratory, Toronto General Hospital, Toronto, Ontario M5G 2C4, Canada.
authors.forename: Kumaraswamy
authors.initials: K
authors.lastname: Nanthakumar
authors.affiliation: McEwen Center for Regenerative Medicine, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Keller
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sefton
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.|Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 1L7, Canada.|The Heart and Stroke/Richard Lewar Centre of Excellence, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Milica
authors.initials: M
authors.lastname: Radisic
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D005269:Femur / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D016062:Porosity; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials