High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling
Microphysiological systems (MPS), comprising human cell cultured in formats that capture features of the three-dimensional (3D) microenvironments of native human organs under microperfusion, are promising tools for biomedical research. Here we report the development of a mesoscale physiological syst...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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IOP Publishing
2021
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| Online Access: | https://hdl.handle.net/1721.1/138752 |
| _version_ | 1811079043858038784 |
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| author | Sphabmixay, Pierre Raredon, Micha Sam Brickman Wang, Alex J-S Lee, Howon Hammond, Paula T Fang, Nicholas X Griffith, Linda G |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Sphabmixay, Pierre Raredon, Micha Sam Brickman Wang, Alex J-S Lee, Howon Hammond, Paula T Fang, Nicholas X Griffith, Linda G |
| author_sort | Sphabmixay, Pierre |
| collection | MIT |
| description | Microphysiological systems (MPS), comprising human cell cultured in formats that capture features of the three-dimensional (3D) microenvironments of native human organs under microperfusion, are promising tools for biomedical research. Here we report the development of a mesoscale physiological system (MePS) enabling the long-term 3D perfused culture of primary human hepatocytes at scales of over 106cells per MPS. A central feature of the MePS, which employs a commercially-available multiwell bioreactor for perfusion, is a novel scaffold comprising a dense network of nano- and micro-porous polymer channels, designed to provide appropriate convective and diffusive mass transfer of oxygen and other nutrients while maintaining physiological values of shear stress. The scaffold design is realized by a high resolution stereolithography fabrication process employing a novel resin. This new culture system sustains mesoscopic hepatic tissue-like cultures with greater hepatic functionality (assessed by albumin and urea synthesis, and CYP3A4 activity) and lower inflammation markers compared to comparable cultures on the commercial polystyrene scaffold. To illustrate applications to disease modeling, we established an insulin-resistant phenotype by exposing liver cells to hyperglycemic and hyperinsulinemic media. Future applications of the MePS include the co-culture of hepatocytes with resident immune cells and the integration with multiple organs to model complex liver-associated diseases. |
| first_indexed | 2024-09-23T11:09:10Z |
| format | Article |
| id | mit-1721.1/138752 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:09:10Z |
| publishDate | 2021 |
| publisher | IOP Publishing |
| record_format | dspace |
| spelling | mit-1721.1/1387522023-04-14T20:04:02Z High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling Sphabmixay, Pierre Raredon, Micha Sam Brickman Wang, Alex J-S Lee, Howon Hammond, Paula T Fang, Nicholas X Griffith, Linda G Massachusetts Institute of Technology. Department of Mechanical Engineering Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Center for Gynepathology Research Microphysiological systems (MPS), comprising human cell cultured in formats that capture features of the three-dimensional (3D) microenvironments of native human organs under microperfusion, are promising tools for biomedical research. Here we report the development of a mesoscale physiological system (MePS) enabling the long-term 3D perfused culture of primary human hepatocytes at scales of over 106cells per MPS. A central feature of the MePS, which employs a commercially-available multiwell bioreactor for perfusion, is a novel scaffold comprising a dense network of nano- and micro-porous polymer channels, designed to provide appropriate convective and diffusive mass transfer of oxygen and other nutrients while maintaining physiological values of shear stress. The scaffold design is realized by a high resolution stereolithography fabrication process employing a novel resin. This new culture system sustains mesoscopic hepatic tissue-like cultures with greater hepatic functionality (assessed by albumin and urea synthesis, and CYP3A4 activity) and lower inflammation markers compared to comparable cultures on the commercial polystyrene scaffold. To illustrate applications to disease modeling, we established an insulin-resistant phenotype by exposing liver cells to hyperglycemic and hyperinsulinemic media. Future applications of the MePS include the co-culture of hepatocytes with resident immune cells and the integration with multiple organs to model complex liver-associated diseases. 2021-12-21T13:41:23Z 2021-12-21T13:41:23Z 2021-10-01 2021-12-21T13:38:22Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/138752 Sphabmixay, Pierre, Raredon, Micha Sam Brickman, Wang, Alex J-S, Lee, Howon, Hammond, Paula T et al. 2021. "High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling." Biofabrication, 13 (4). en 10.1088/1758-5090/ac23aa Biofabrication Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf IOP Publishing IOP Publishing |
| spellingShingle | Sphabmixay, Pierre Raredon, Micha Sam Brickman Wang, Alex J-S Lee, Howon Hammond, Paula T Fang, Nicholas X Griffith, Linda G High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling |
| title | High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling |
| title_full | High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling |
| title_fullStr | High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling |
| title_full_unstemmed | High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling |
| title_short | High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling |
| title_sort | high resolution stereolithography fabrication of perfusable scaffolds to enable long term meso scale hepatic culture for disease modeling |
| url | https://hdl.handle.net/1721.1/138752 |
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