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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.
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Mechanical interaction between a hydrogel and an embedded cell in biomicrofluidic applications
Thanks to their softness, biocompatibility, porosity, and ready availability, hydrogels are commonly used in microfluidic assays and organ-on-chip devices as a matrix for cells. They not only provide a supporting scaffold for the differentiating cells and the developing organoids, but also serve as the medium for transmitting oxygen, nutrients, various chemical factors, and mechanical stimuli to the cells. From a bioengineering viewpoint, the transmission of forces from fluid perfusion to the cells through the hydrogel is critical to the proper function and development of the cell colony. In this paper, we develop a poroelastic model to represent the fluid flow through a hydrogel containing a biological cell modeled as a hyperelastic inclusion. In geometries representing shear and normal flows that occur frequently in microfluidic experiments, we use finite-element simulations to examine how the perfusion engenders interstitial flow in the gel and displaces and deforms the embedded cell. The results show that pressure is the most important stress component in moving and deforming the cell, and the model predicts the velocity in the gel and stress transmitted to the cell that is comparable to in vitro and in vivo data. This work provides a computational tool to design the geometry and flow conditions to achieve optimal flow and stress fields inside the hydrogels and around the cell.
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- PAR ID:
- 10620672
- Publisher / Repository:
- API Publishing
- Date Published:
- Journal Name:
- Biomicrofluidics
- Volume:
- 19
- Issue:
- 2
- ISSN:
- 1932-1058
- Page Range / eLocation ID:
- 024104
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1063/5.0263344
