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Gelation Kinetics and Mechanical Properties of Thiol-Tetrazole Methylsulfone Hydrogels Designed for Cell Encapsulation

  • Hydrogel precursors that crosslink within minutes are essential for the development of cell encapsulation matrices and their implementation in automated systems. Such timescales allow sufficient mixing of cells and hydrogel precursors under low shear forces and the achievement of homogeneous networks and cell distributions in the 3D cell culture. The previous work showed that the thiol-tetrazole methylsulfone (TzMS) reaction crosslinks star-poly(ethylene glycol) (PEG) hydrogels within minutes at around physiological pH and can be accelerated or slowed down with small pH changes. The resulting hydrogels are cytocompatible and stable in cell culture conditions. Here, the gelation kinetics and mechanical properties of PEG-based hydrogels formed by thiol-TzMS crosslinking as a function of buffer, crosslinker structure and degree of TzMS functionality are reported. Crosslinkers of different architecture, length and chemical nature (PEG versus peptide) are tested, and degree of TzMS functionality is modified by inclusion of RGD cell-adhesive ligand, all at concentration ranges typically used in cell culture. These studies corroborate that thiol/PEG-4TzMS hydrogels show gelation times and stiffnesses that are suitable for 3D cell encapsulation and tunable through changes in hydrogel composition. The results of this study guide formulation of encapsulating hydrogels for manual and automated 3D cell culture.

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Document Type:Article
Author:Adrián de Miguel-Jiménez, Bastian Ebeling, Julieta I. PaezORCiD, Claudia Fink-Straube, Samuel Pearson, Aránzazu del Campo BécaresORCiD
Parent Title (English):Macromolecular Bioscience
First Page:2200419
Year of first Publication:2023
Release Date:2023/02/23
Tag:cell culture; cell encapsulation; crosslinking; gelation; hydrogel
Impact:05.859 (2021)
Funding Information:European Union's Horizon 2020 research and innovation program under the FET PROACTIVE grant agreement no. 731957 (Mechano-Control) . Senatsausschuss Wettbewerb (SAW) Leibniz-Transfer program under project uTissueFab. Deutsche Forschungsgemeinschaft (DFG, project no. 422041745).
Groups:Chemische Analytik
Dynamische Biomaterialien
DDC classes:500 Naturwissenschaften und Mathematik / 540 Chemie
Open Access:Open Access
Signature:INM 2023/014
Licence (German):License LogoCreative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International