3-D Life PVA-CD Hydrogel Used in Microfluidic Platform to Model and Assess Cellular Barriers
Introduction
The Cellendes 3-D Life PVA-CD Hydrogel SG Kit has been cited in Biosensors in an interesting study by Arya Lekshmi Nair et al. 2021, "Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to Study the Interaction of 3D Tumor Spheroids with Cellular Barriers."
Publication
Endothelial and epithelial cellular barriers have critical involvement in transport of solutes and other molecules. In cases of inflammation and disease, the function of these barriers can be affected. Thus, a relevant in vitro model of cellular barriers would represent an extremely valuable tool in the investigation of disease mechanisms and also for use in drug screening and drug discovery.
The researchers in this study set out to use "microfluidic technology to model cellular barriers in a parallelizable microfluidic platform manufactured by microinjection molding of cyclic olefin copolymer (COC) comprising integrated electrodes to enable real-time transepithelial/transendothelial electrical resistance (TEER) measurement."
To demonstrate the capability of this microfluidic platform, the researchers used 3-D Life PVA-CD Hydrogel SG Kit to generate co-cultures of tumor cells growing in a hydrogel mimicking tumor extracellular matrix (ECM) along with a cellular barrier.
Figure 1. Chip technology: (A) precision injection molded device with multi-well-plate footprint, comprising 10 culture areas C1 to C10 with two channels, inlets and outlets per culture area. (B) Electrodes line the culture area with contact pads positioned at the plate edge (A). (C) Within the culture areas, both channels are separated by an array of pillars. Aqueous, low viscous hydrogel solution with or without cells may be introduced in one of the channels (“abluminal channel”) whereby gaps between pillars act as capillary stop valves preventing spilling of the gel solution into the adjacent channel (“perfusion channel” or “luminal channel”). (D) Scheme of tumor–vascular interface showing endothelial barrier (1) with cells forming tight junctions (2). Blood flow results in shear forces (3). Immune cells (4) invade tissue to attack tumor tissue (5). (E) Scheme of chip according to this study mimicking the tumor–vascular micro-environment by co-culture of tumor spheroids (5) in a hydrogel matrix with a cellular barrier (1) grown on the interface formed between pillars (4). Electrodes (6) located at the periphery of both channels enable measurement of the electrical impedance across the interface.
Citation
This content has been adapted from the paper cited below. You can find the entire paper via the link:
Nair, Arya Lekshmi et al. “Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to Study the Interaction of 3D Tumor Spheroids with Cellular Barriers.” Biosensors vol. 11,9 314. 3 Sep. 2021, doi:10.3390/bios11090314
Product Spotlight
The mentioned study used the 3-D Life PVA-CD Hydrogel SG Kit to form the hydrogel that was used to fill the microfluidic chip. This kit is consists of two main components: a thiol-reactive polyvinyl alcohol (PVA) polymer and a thiol-functionalized crosslinker (CD-Link). CD-Link contains a matrix metalloproteinase (MMP)-cleavable peptide sequence, which is cleaved by a broad range of MMPs including MMP1, MMP3, MMP7 and MMP9. It allows cells to migrate within the gel, if they produce the indicated MMPs.
Gelation time varies with pH and can be adjusted by mixing two ten-fold concentrated buffers (10× CB pH 7.2 and 10× CB pH 5.5). The lower the pH, the slower the gel formation.
The hydrogel in this study made use of the 3-D Life RGD Peptide, which can be covalently attached to a portion of the SH-reactive groups of SG-PVA to provide a cell-adhesive matrix.
The resulting hydrogel in this study served as a chemically defined hydrogel that supported prolonged growth and adhesion of Madin-Darby Canine Kidney (MDCK) cells, with the MMP-cleavable CD-link enabling remodeling by 3D tumor spheroids and their outgrowth into the perfusion channel.
Ilex Life Sciences LLC is an official distributor of Cellendes GmbH 3-D Life hydrogel products. To learn more about 3-D Life hydrogels, please visit 3-D Life Biomimetic Hydrogels.