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

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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.

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