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Gelation kinetics of thiol-methylsulfone (MS) hydrogel formulations for 3D cell culture

  • Crosslinking chemistries that allow hydrogel formation within minutes are essential to achieve homogeneous networks and cell distributions in 3D cell culture. Thiol-methylsulfone (MS) crosslinking chemistry offers minutes-scale gelation under near-physiological conditions showing many desirable attributes for 3D cell encapsulation. Here we investigate the gelation kinetics and mechanical properties of PEG-based hydrogels formed by thiol-tetrazole methylsulfone (TzMS) crosslinking as a function of buffer, crosslinker structure, and degree of TzMS functionalization. Appropriate buffer selection ensured constant pH throughout crosslinking. The formulation containing cell adhesive ligand RGD and enzymatically-degradable peptide VPM gelled in ca. 4 min at pH 7.5, and stiffness could be increased from hundreds of Pascals to > 1 kPa by using excess VPM. The gelation times and stiffnesses for these hydrogels are highly suitable for 3D cell encapsulations, and pave the way for reliable 3D cell culture workflows in pipetting robots.

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Document Type:Preprint
Author:Adrian de Miguel-Jiménez, Bastian Ebeling, Julieta I. PaezORCiD, Claudia Fink-Straube, Samuel Pearson, Aránzazu del Campo BécaresORCiD
Parent Title (English):chemRxiv
Date of first Publication:2022/10/03
Release Date:2022/11/18
Tag:cell culture; cell encapsulation; crosslinking; gelation; hydrogel
Groups:Chemische Analytik
Dynamische Biomaterialien
Open Access:Open Access
Signature:INM 2022/102_preprint
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International