Issue 17, 2022

Modular mixing of benzene-1,3,5-tricarboxamide supramolecular hydrogelators allows tunable biomimetic hydrogels for control of cell aggregation in 3D

Abstract

Few synthetic hydrogels can mimic both the viscoelasticity and supramolecular fibrous structure found in the naturally occurring extracellular matrix (ECM). Furthermore, the ability to control the viscoelasticity of fibrous supramolecular hydrogel networks to influence cell culture remains a challenge. Here, we show that modular mixing of supramolecular architectures with slow and fast exchange dynamics can provide a suitable environment for multiple cell types and influence cellular aggregation. We employed modular mixing of two synthetic benzene-1,3,5-tricarboxamide (BTA) architectures: a small molecule water-soluble BTA with slow exchange dynamics and a telechelic polymeric BTA-PEG-BTA with fast exchange dynamics. Copolymerisation of these two supramolecular architectures was observed, and all tested formulations formed stable hydrogels in water and cell culture media. We found that rational tuning of mechanical and viscoelastic properties is possible by mixing BTA with BTA-PEG-BTA. These hydrogels showed high viability for both chondrocyte (ATDC5) and human dermal fibroblast (HDF) encapsulation (>80%) and supported neuronal outgrowth (PC12 and dorsal root ganglion, DRG). Furthermore, ATDC5s and human mesenchymal stem cells (hMSCs) were able to form spheroids within these viscoelastic hydrogels, with control over cell aggregation modulated by the dynamic properties of the material. Overall, this study shows that modular mixing of supramolecular architectures enables tunable fibrous hydrogels, creating a biomimetic environment for cell encapsulation. These materials are suitable for the formation and culture of spheroids in 3D, critical for upscaling tissue engineering approaches towards cell densities relevant for physiological tissues.

Graphical abstract: Modular mixing of benzene-1,3,5-tricarboxamide supramolecular hydrogelators allows tunable biomimetic hydrogels for control of cell aggregation in 3D

Supplementary files

Article information

Article type
Paper
Submitted
01 mar 2022
Accepted
31 mai 2022
First published
21 jul 2022
This article is Open Access
Creative Commons BY-NC license

Biomater. Sci., 2022,10, 4740-4755

Modular mixing of benzene-1,3,5-tricarboxamide supramolecular hydrogelators allows tunable biomimetic hydrogels for control of cell aggregation in 3D

S. Hafeez, F. R. Passanha, A. J. Feliciano, F. A. A. Ruiter, A. Malheiro, R. P. M. Lafleur, N. M. Matsumoto, C. van Blitterswijk, L. Moroni, P. Wieringa, V. L. S. LaPointe and M. B. Baker, Biomater. Sci., 2022, 10, 4740 DOI: 10.1039/D2BM00312K

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