Issue 18, 2024

Supported gel slab scaffolds as a three-dimensional cell-based assay platform

Abstract

Cell-based assays are heavily relied on in the drug discovery pipeline, quickly pairing down large compound libraries to a manageable number of drug candidates for further characterization and evaluation. Monolayer cultures in which cells are deposited onto the bottom of well plates are the workhorse of many of these screens despite continued evidence of their inability to predict in vivo responses. Three-dimensional (3D) culture platforms can generate tissue-like environments with more representative cellular phenotypes than monolayers but have proven challenging to incorporate into already-developed workflows. Scaffold-based approaches are a tractable means of generating tissue-like environments, supporting cell-laden gels whose preparation is analogous to depositing cells in a well plate. Here, we describe supported gel slab (SGS) scaffolds prepared from commercially available materials, an adhesive spray, and a laser cutter. These cell-containing scaffolds can readily fit into well plates, providing a format compatible with current liquid handlers and analytical instrumentation. The scaffolds enable the evaluation of cellular responses in individual or stacked structures, which contain extracellular matrix-rich microenvironments. With a series of demonstrations, we highlight the utility of the readily assembled SGS scaffolds to quantify cellular responses. These readouts include confocal microscopy, quantifying cellular invasion in Transwell-like and stacked formats, generating multilayered spheroid-on-demand structures capable of providing spatially resolved maps of drug responses, and identifying potential chemotherapies in a screening application.

Graphical abstract: Supported gel slab scaffolds as a three-dimensional cell-based assay platform

Supplementary files

Article information

Article type
Paper
Submitted
17 May 2024
Accepted
19 Jul 2024
First published
22 Jul 2024

Analyst, 2024,149, 4653-4662

Supported gel slab scaffolds as a three-dimensional cell-based assay platform

Z. R. Sitte, E. E. Karlsson, T. S. Larson, H. Li, H. Zhou and M. R. Lockett, Analyst, 2024, 149, 4653 DOI: 10.1039/D4AN00691G

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements