Redox-responsive functionalized hydrogel marble for the generation of cellular spheroids
Graphical abstract
Section snippets
Materials
PTE-200 SH (Sunbright) (4-arm PEG-((CH2)2-SH)4, Mw 20 kDa) was purchased by the NOF Corporation (Tokyo, Japan). Gelatin type A and poly(tetrafluoroethylene) (PTFE; particle size: 1 μm) were supplied by Sigma–Aldrich (St. Louis, MO, USA). Horseradish peroxidase (HRP; activity: 100 unit/mg) was supplied by Wako Pure Chemical Industries (Osaka, Japan). Glycyl-l-tyrosine hydrate (Gly–Tyr), l-cysteine (Cys), 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide (EDC), and squalene oil were acquired by
Physicochemical properties of hydrogel marbles prepared by HRP catalysis under various Gela-SH concentrations
The physicochemical properties of HMs depend on the intrinsic properties of the polymer backbone. The HMs were prepared by incorporating four components (4-arm PEG-SH, Gela-SH, HRP, and Gly–Tyr) for hydrogelation and covering a droplet of this solution in a superhydrophobic powder (Fig. 1A and B, i). The HMs can be produced with any desired volume between 10 and 50 μL (Fig. 1B, ii), which results in HMs with diameters around 2.5–4.5 mm. Drops with large volumes (50 μL) of aqueous polymer tended
Discussion
Many approaches have been proposed for the fabrication of 3D cellular spheroids (25, 26, 27, 28, 29). Among them, hydrogels have been the most widely studied as 3D cell culture in the past decade as they enable biomimetic extracellular matrix (30). Normally, the hydrogelation process requires hydrogen peroxide (H2O2) for HRP-catalyzed gelation. However, too much H2O2 may negatively impact the biological components in the hydrogel system (21). Therefore, in previous studies, we developed a novel
Acknowledgments
This work was supported by the Japan Society for the Promotion of Science, JSPS KAKENHI (grant numbers JP17K19016 and JP19H00841 to N.K. and JP16H06369 to M.G.). The authors would like to thank Mr. Yusei Hamada for his essential help and technical support in the initial stage of this research. We also thank Stephanie Knowlton, PhD, from Liwen Bianji, Edanz Editing China, for editing the English text of a draft of this manuscript.
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