Modular mixing of benzene-1,3,5-tricarboxamide supramolecular hydrogelators allows tunable biomimetic hydrogels for control of cell aggregation in 3D.
Shahzad Hafeez, Fiona R Passanha, Antonio J Feliciano, Floor A A Ruiter, Afonso Malheiro, René P M Lafleur, Nicholas M Matsumoto, Clemens van Blitterswijk, Lorenzo Moroni, Paul Wieringa, Vanessa L S LaPointe, Matthew B Baker
Author Information
Shahzad Hafeez: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. m.baker@maastrichtuniversity.nl. ORCID
Fiona R Passanha: Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Antonio J Feliciano: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. m.baker@maastrichtuniversity.nl.
Floor A A Ruiter: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. m.baker@maastrichtuniversity.nl.
Afonso Malheiro: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. m.baker@maastrichtuniversity.nl.
René P M Lafleur: Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands. ORCID
Nicholas M Matsumoto: Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Clemens van Blitterswijk: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. m.baker@maastrichtuniversity.nl.
Lorenzo Moroni: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. m.baker@maastrichtuniversity.nl. ORCID
Paul Wieringa: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. m.baker@maastrichtuniversity.nl. ORCID
Vanessa L S LaPointe: Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. ORCID
Matthew B Baker: Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. m.baker@maastrichtuniversity.nl. ORCID
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.
References
J Am Chem Soc. 2020 Sep 9;142(36):15371-15385
[PMID: 32808783]
