Cancer cells grown in a three-dimensional (3D) environment have been shown to better replicate in vivo conditions including cell-to-cell interactions, metabolite and drug transfer, and population heterogeneity all of which are lacking in 2D culturing approaches. There is significant interest in developing new approaches for culturing mammalian cells in a 3D environment. One approach is to use polymeric materials (e.g., hydrogels) as a scaffold which can be synthesized from biologically derived or synthetic materials. However, biological hydrogels are often limited by batch-to-batch heterogeneity, while synthetic hydrogels require external initiation to polymerize which can adversely affect cell viability for biological application. The goal of this work was to develop a thiol-acrylate, biodegradable hydrogel that possesses highly tunable properties and acts as a scaffold to support 3D cell culture. Six different hydrogel formulations were synthesized using two readily available thiol (ETTMP 1300) and acrylate (PEGDA 700) monomers, polymerized by a base-catalyzed Michael addition reaction. Tuning the molar ratio of the thiol and acrylate and weight percentage of polymer was shown to modulate the gelation time, stiffness and stability of the hydrogel offering a greater degree of control and reproducibility. Increasing the weight percentage of polymer and molar ratio of thiol to acrylate (1 to 1.05) significantly reduced gelation time, increased stiffness, and stability of the resultant hydrogel. The hydrogel formulations with a thiol-to-acrylate molar ratio of 1.05 were found to be the optimal approach for both 2D and 3D culture as demonstrated by viable cellular aggregates of the triple negative breast cancer cell line MDA-MB-231 present after 17 days of 3D continuous culture. Finally, MCF7 cells (an ER+ breast cancer cell line known to form spheroids) were observed to form 3D spheroids up to 600 µm in diameter as proof-of-principle for the thiol-acrylate hydrogel to function as a scaffold for 3D cell culture. A comparison of the different mechanical properties of the six hydrogel formulations, coupled with in vitro cell culture results and findings from previously published hydrogels suggests that it is a novel synthetic polymeric scaffold capable of supporting of 3D cell culture.

Synthesis and characterization of thiol-acrylate hydrogels using a base-catalyzed Michael addition for 3D cell culture applications

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.