Pulsed Microfluid Force-Based On-Chip Modular Fabrication for Liver Lobule-Like 3D Cellular Models
Open Access
- 8 April 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Thinking Skills and Creativity
- Vol. 2021, 9871396
- https://doi.org/10.34133/2021/9871396
Abstract
In vitro three-dimensional (3D) cellular models with native tissue-like architectures and functions have potential as alternatives to human tissues in regenerative medicine and drug discovery. However, it is difficult to replicate liver constructs that mimic in vivo microenvironments using current approaches in tissue engineering because of the vessel-embedded 3D structure and complex cell distribution of the liver. This paper reports a pulsed microflow-based on-chip 3D assembly method to construct 3D liver lobule-like models that replicate the spatial structure and functions of the liver lobule. The heterogeneous cell-laden assembly units with hierarchical cell distribution are fabricated through multistep photopatterning of different cell-laden hydrogels. Through fluid force interaction by pulsed microflow, the hierarchical assembly units are driven to a stack, layer by layer, and thus spatially assemble into 3D cellular models in the closed liquid chamber of the assembly chip. The 3D models with liver lobule-like hexagonal morphology and radial cell distribution allow the dynamic perfusion culture to maintain high cell viability and functional expression during long-term culture in vitro. These results demonstrate that the fabricated 3D liver lobule-like models are promising for drug testing and the study of individual diagnoses and treatments.Keywords
Funding Information
- National Natural Science Foundation of China (61520106011)
- National Key R&D Program of China (2019YFB1309702)
This publication has 45 references indexed in Scilit:
- Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADMEArchives of Toxicology, 2013
- Three‐Dimensional Fluidic Self‐Assembly by Axis Translation of Two‐Dimensionally Fabricated Microcomponents in Railed MicrofluidicsSmall, 2011
- Preparation of arrays of cell spheroids and spheroid-monolayer cocultures within a microfluidic deviceJournal of Bioscience and Bioengineering, 2010
- Cell-laden microengineered gelatin methacrylate hydrogelsBiomaterials, 2010
- Layer by Layer Three-dimensional Tissue Epitaxy by Cell-Laden Hydrogel DropletsTissue Engineering, Part C: Methods, 2010
- Characterization of cell viability during bioprinting processesBiotechnology Journal, 2009
- Maturation of the Extracellular Matrix and Cell Adhesion Molecules in Layered Co-cultures of HepG2 and Endothelial CellsThe Journal of Biochemistry, 2009
- Directed assembly of cell-laden microgels for fabrication of 3D tissue constructsProceedings of the National Academy of Sciences of the United States of America, 2008
- Capturing complex 3D tissue physiology in vitroNature Reviews Molecular Cell Biology, 2006
- Tissue EngineeringScience, 1993