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Variable gelation time and stiffness of low-molecular-weight hydrogels through catalytic control over self-assembly

Nature Protocols volume 9, pages 977–988 (2014)Cite this article

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Abstract

This protocol details the preparation of low-molecular-weight hydrogels (LMWGs) in which the gelation time and mechanical stiffness of the final gel can be tuned with the concentration of the catalyst used in the in situ formation of the hydrogelator. By altering the rate of formation of the hydrazone-based gelator from two water-soluble compounds—an oligoethylene functionalized benzaldehyde and a cyclohexane-derived trishydrazide—in the presence of acid or aniline as catalyst, the kinetics of gelation can be tuned from hours to minutes. The resulting materials display controllable stiffness in the 5–50 kPa range. This protocol works at ambient temperatures in water, at either neutral or moderately acidic pH (phosphate buffer, pH 5) depending on the catalyst used. The hydrazide and aldehyde precursors take a total of 5 d to prepare. The final gel is prepared by mixing aqueous solutions of the two precursors and can take between minutes and hours to set, depending on the catalytic conditions. We also describe analysis of the hydrogels by critical gel concentration (CGC) tests, rheology and confocal laser-scanning microscopy (CLSM).

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Figure 1: Scheme of the general concept.
Figure 2: Cyclohexane core gelator designs.
Figure 3: Catalytic formation of trishydrazone hydrogelator 3 from soluble building blocks 1 and 2 leads to supersaturation followed by formation of fibers that eventually cross-link to form a network that traps the surrounding solvent, leading to gelation.
Figure 4: Gel formation and formation dynamics depend on catalyst loading.
Figure 5: Influence of catalysis on material morphology.
Figure 6: Synthesis of the gelator building blocks.
Figure 7: Confocal microscopy.
Figure 8: 1H-NMR spectra of intermediate products 4 and 5.
Figure 9: Demonstration of applying a rheometer sample.

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Acknowledgements

We thank the Netherlands Organisation for Scientific Research (NWO; an ECHO grant and a VIDI grant) for funding.

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Authors and Affiliations

  1. Department of Chemical Engineering, Advanced Soft Matter, Delft University of Technology, Delft, The Netherlands

    Jos M Poolman, Job Boekhoven, Anneke Besselink, Alexandre G L Olive, Jan H van Esch & Rienk Eelkema

  2. Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, Illinois, USA

    Job Boekhoven

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  1. Jos M Poolman
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Contributions

J.M.P., J.B., A.B. and A.G.L.O. performed the experiments and analyzed the data, R.E. and J.H.v.E. designed the experiments, J.M.P. and R.E. wrote the paper, and all authors contributed to discussing the results and editing the manuscript.

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Correspondence to Jan H van Esch or Rienk Eelkema.

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The authors declare no competing financial interests.

Supplementary information

Acid-catalyzed hydrogel formation.

Formation of a hydrazone-based hydrogel under acid-catalyzed conditions, by mixing buffered stock solutions of aldehyde and hydrazide at room temperature. (MOV 9170 kb)

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Poolman, J., Boekhoven, J., Besselink, A. et al. Variable gelation time and stiffness of low-molecular-weight hydrogels through catalytic control over self-assembly. Nat Protoc 9, 977–988 (2014). https://doi.org/10.1038/nprot.2014.055

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