A Novel High‐Speed Production Process to Create Modular Components for the Bottom‐Up Assembly of Large‐Scale Tissue‐Engineered Constructs

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.