High resolution stereolithography fabrication of perfusable scaffolds to enable long-term meso-scale hepatic culture for disease modeling
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Sphabmixay_2021_Biofabrication_13_045024.pdf
Description
Published version
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5.87 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Sphabmixay, Pierre
Raredon, Micha Sam Brickman
Wang, Alex J-S
Lee, Howon
Hammond, Paula T
Fang, Nicholas X
Griffith, Linda G
Date Issued
October 1, 2021
Journal
Biofabrication
Publisher
IOP Publishing
Citation
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).
Version
Final published version
Abstract
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.
MIT Department
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
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1088/1758-5090/ac23aa
