Hydrogel-based microfluidic device with multiplexed 3D in vitro cell culture
Abstract Microfluidic devices that combine an extracellular matrix environment, cells, and physiologically relevant perfusion, are advantageous as cell culture platforms. We developed a hydrogel-based, microfluidic cell culture platform by loading polyethylene glycol (PEG) hydrogel-encapsulated U87...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22439-y |
| _version_ | 1811249934890958848 |
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| author | Allison Clancy Dayi Chen Joseph Bruns Jahnavi Nadella Samuel Stealey Yanjia Zhang Aaron Timperman Silviya P. Zustiak |
| author_facet | Allison Clancy Dayi Chen Joseph Bruns Jahnavi Nadella Samuel Stealey Yanjia Zhang Aaron Timperman Silviya P. Zustiak |
| author_sort | Allison Clancy |
| collection | DOAJ |
| description | Abstract Microfluidic devices that combine an extracellular matrix environment, cells, and physiologically relevant perfusion, are advantageous as cell culture platforms. We developed a hydrogel-based, microfluidic cell culture platform by loading polyethylene glycol (PEG) hydrogel-encapsulated U87 glioblastoma cells into membrane-capped wells in polydimethyl siloxane (PDMS). The multilayer microfluidic cell culture system combines previously reported design features in a configuration that loads and biomimetically perfuses a 2D array of cell culture chambers. One dimension of the array is fed by a microfluidic concentration gradient generator (MCGG) while the orthogonal dimension provides loading channels that fill rows of cell culture chambers in a separate layer. In contrast to typical tree-like MCGG mixers, a fractional serial dilution of 1, ½, ¼, and 0 of the initial solute concentration is achieved by tailoring the input microchannel widths. Hydrogels are efficiently and reproducibly loaded in all wells and cells are evenly distributed throughout the hydrogel, maintaining > 90% viability for up to 4 days. In a drug screening assay, diffusion of temozolomide and carmustine to hydrogel-encapsulated U87 cells from the perfusion solution is measured, and dose–response curves are generated, demonstrating utility as an in vitro mimic of the glioblastoma microenvironment. |
| first_indexed | 2024-04-12T15:55:07Z |
| format | Article |
| id | doaj.art-7e4a80b2fe864a4697cc7fe8685a6d34 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T15:55:07Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7e4a80b2fe864a4697cc7fe8685a6d342022-12-22T03:26:23ZengNature PortfolioScientific Reports2045-23222022-10-0112111310.1038/s41598-022-22439-yHydrogel-based microfluidic device with multiplexed 3D in vitro cell cultureAllison Clancy0Dayi Chen1Joseph Bruns2Jahnavi Nadella3Samuel Stealey4Yanjia Zhang5Aaron Timperman6Silviya P. Zustiak7Department of Biomedical Engineering, Saint Louis UniversityDepartment of Bioengineering, and Biochemistry and Biophysics, University of PennsylvaniaDepartment of Biomedical Engineering, Saint Louis UniversityDepartment of Biomedical Engineering, Saint Louis UniversityDepartment of Biomedical Engineering, Saint Louis UniversityDepartment of Bioengineering, and Biochemistry and Biophysics, University of PennsylvaniaDepartment of Bioengineering, and Biochemistry and Biophysics, University of PennsylvaniaDepartment of Biomedical Engineering, Saint Louis UniversityAbstract Microfluidic devices that combine an extracellular matrix environment, cells, and physiologically relevant perfusion, are advantageous as cell culture platforms. We developed a hydrogel-based, microfluidic cell culture platform by loading polyethylene glycol (PEG) hydrogel-encapsulated U87 glioblastoma cells into membrane-capped wells in polydimethyl siloxane (PDMS). The multilayer microfluidic cell culture system combines previously reported design features in a configuration that loads and biomimetically perfuses a 2D array of cell culture chambers. One dimension of the array is fed by a microfluidic concentration gradient generator (MCGG) while the orthogonal dimension provides loading channels that fill rows of cell culture chambers in a separate layer. In contrast to typical tree-like MCGG mixers, a fractional serial dilution of 1, ½, ¼, and 0 of the initial solute concentration is achieved by tailoring the input microchannel widths. Hydrogels are efficiently and reproducibly loaded in all wells and cells are evenly distributed throughout the hydrogel, maintaining > 90% viability for up to 4 days. In a drug screening assay, diffusion of temozolomide and carmustine to hydrogel-encapsulated U87 cells from the perfusion solution is measured, and dose–response curves are generated, demonstrating utility as an in vitro mimic of the glioblastoma microenvironment.https://doi.org/10.1038/s41598-022-22439-y |
| spellingShingle | Allison Clancy Dayi Chen Joseph Bruns Jahnavi Nadella Samuel Stealey Yanjia Zhang Aaron Timperman Silviya P. Zustiak Hydrogel-based microfluidic device with multiplexed 3D in vitro cell culture Scientific Reports |
| title | Hydrogel-based microfluidic device with multiplexed 3D in vitro cell culture |
| title_full | Hydrogel-based microfluidic device with multiplexed 3D in vitro cell culture |
| title_fullStr | Hydrogel-based microfluidic device with multiplexed 3D in vitro cell culture |
| title_full_unstemmed | Hydrogel-based microfluidic device with multiplexed 3D in vitro cell culture |
| title_short | Hydrogel-based microfluidic device with multiplexed 3D in vitro cell culture |
| title_sort | hydrogel based microfluidic device with multiplexed 3d in vitro cell culture |
| url | https://doi.org/10.1038/s41598-022-22439-y |
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