TY - JOUR
T1 - Thiol-Methylsulfone-Based Hydrogels for 3D Cell Encapsulation
AU - Paez, Julieta I.
AU - Farrukh, Aleeza
AU - Valbuena-Mendoza, Rocío
AU - Włodarczyk-Biegun, Małgorzata K.
AU - Del Campo, Aránzazu
N1 - Funding Information:
J.I.P., R.V.M., and A.d.C. received funding from the European Union’s Horizon 2020 research and innovation program under the FET PROACTIVE grant agreement no. 731957 (Mechano-Control). J.I.P. received funding from the Deutsche Forschungsgemeinschaft (DFG, Project no. 422041745).
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/2/19
Y1 - 2020/2/19
N2 - 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.
AB - 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.
KW - 3D cell culture
KW - gelation kinetics
KW - gelation under physiological conditions
KW - heteroaromatic methylsulfones
KW - hydrogels
KW - thiol-mediated cross-linking
KW - n/a OA procedure
UR - http://www.scopus.com/inward/record.url?scp=85080095028&partnerID=8YFLogxK
U2 - 10.1021/acsami.0c00709
DO - 10.1021/acsami.0c00709
M3 - Article
C2 - 31999422
AN - SCOPUS:85080095028
SN - 1944-8244
VL - 12
SP - 8062
EP - 8072
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 7
ER -