Khan Omar F, Voice Derek N, Leung Brendan M, Sefton Michael V
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.
Adv Healthc Mater. 2015 Jan 7;4(1):113-20. doi: 10.1002/adhm.201400150. Epub 2014 Jun 3.
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.
为了替换受损或患病组织，可以通过自下而上的方法组装模块化组件来制备大型组织工程构建体。然而，需要一种高速方法来生产足够数量的这些模块以用于全尺寸的组织替代物。为此，设计了一种新颖的生产技术，该技术结合了空气剪切和活塞流反应器式设计，以快速生产大量具有可调直径和长度的水凝胶基（此处为I型胶原蛋白）圆柱形模块化组件。使用该技术，含有NIH 3T3细胞的模块显示出大于95%的活力，同时证明了内皮细胞表面附着和汇合单层形成。此外，快速生产的模块用于在体外组装大型组织构建体（>1 cm³）。将含有表达荧光素酶的L929细胞的模块构建块填充到全尺寸成年大鼠肝脏形状的生物反应器中并用细胞培养基灌注，以证明构建器官形状构建体的能力；生物发光证明在3天内具有持续的活力。嵌入心肌细胞的模块也用于组装可电刺激的收缩组织。
