title: A novel high-speed production process to create modular components for the bottom-up assembly of large-scale tissue-engineered constructs.
abstract: To replace damaged or diseased tissues, large tissue-engineered constructs can be prepared by assembling modular components in a bottom-up approach. However, a high-speed method is needed to produce sufficient numbers of these modules for full-sized tissue substitutes. To this end, a novel production technique is devised, combining air shearing and a plug flow reactor-style design to rapidly produce large quantities of hydrogel-based (here type I collagen) cylindrical modular components with tunable diameters and length. Using this technique, modules containing NIH 3T3 cells show greater than 95% viability while endothelial cell surface attachment and confluent monolayer formation are demonstrated. Additionally, the rapidly produced modules are used to assemble large tissue constructs (>1 cm(3) ) in vitro. Module building blocks containing luciferase-expressing L929 cells are packed in full size adult rat-liver-shaped bioreactors and perfused with cell medium, to demonstrate the capacity to build organ-shaped constructs; bioluminescence demonstrates sustained viability over 3 d. Cardiomyocyte-embedded modules are also used to assemble electrically stimulatable contractile tissue.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5, Canada.
authors.forename: Omar F
authors.initials: OF
authors.lastname: Khan
authors.forename: Derek N
authors.initials: DN
authors.lastname: Voice
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Leung
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sefton
mesh_terms: D000818:Animals; D019149:Bioreactors; D024042:Collagen Type I / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D041681:NIH 3T3 Cells; D051381:Rats; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D024042:Collagen Type I; D020100:Hydrogels
keywords: bioreactors; cardiomyocytes; endothelial cells; scale-up; vasculature