Thiol-Methylsulfone-Based Hydrogels for 3D Cell Encapsulation

Julieta I. Paez*, Aleeza Farrukh, Rocío Valbuena-Mendoza, Małgorzata K. Włodarczyk-Biegun, Aránzazu Del Campo

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

32 Citations (Scopus)

Abstract

Thiol-maleimide and thiol-vinylsulfone cross-linked hydrogels are widely used systems in 3D culture models, in spite of presenting uncomfortable reaction kinetics for cell encapsulation: too fast (seconds for thiol-maleimide) or too slow (minutes-hours for thiol-vinylsulfone). Here, we introduce the thiol-methylsulfone reaction as alternative cross-linking chemistry for cell encapsulation, particularized for PEG-hydrogels. The thiol-methylsulfone reaction occurs at high conversion and at intermediate reaction speed (seconds-minutes) under physiological pH range. These properties allow easy mixing of hydrogel precursors and cells to render homogeneous cell-laden gels at comfortable experimental time scales. The resulting hydrogels are cytocompatible and show comparable hydrolytic stability to thiol-vinylsulfone gels. They allow direct bioconjugation of thiol-derivatized ligands and tunable degradation kinetics by cross-linking with degradable peptide sequences. 3D cell culture of two cell types, fibroblasts and human umbilical vein endothelial cells (HUVECs), is demonstrated.

Original languageEnglish
Pages (from-to)8062-8072
Number of pages11
JournalACS Applied Materials and Interfaces
Volume12
Issue number7
DOIs
Publication statusPublished - 19 Feb 2020
Externally publishedYes

Keywords

  • 3D cell culture
  • gelation kinetics
  • gelation under physiological conditions
  • heteroaromatic methylsulfones
  • hydrogels
  • thiol-mediated cross-linking
  • n/a OA procedure

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