A new boronate ester-based crosslinking strategy allows the design of nonswelling and long-term stable dynamic covalent hydrogels
Nathan Lagneau, L. Terriac, Pierre Tournier, Jean‐Jacques Hélesbeux, Guillaume Viault, Denis Séraphin, Boris Halgand, François Loll, Catherine Garnier, Camille Jonchère, Matthieu Rivière, Arnaud Tessier, J. Lebreton, Yves Maugars, Jérôme Guicheux, Catherine Le Visage, Vianney Delplace
Abstract
Dynamic hydrogels are viscoelastic materials that can be designed to be self-healing, malleable, and injectable, making them particularly interesting for a variety of biomedical applications. To design dynamic hydrogels, dynamic covalent crosslinking reactions are attracting increasing attention. However, dynamic covalent hydrogels tend to swell, and often lack stability. Boronate ester-based hydrogels, which result from the dynamic covalent reaction between a phenylboronic acid (PBA) derivative and a diol, are based on stable precursors, and can therefore address these limitations. Yet, boronate ester formation hardly occurs at physiological pH. To produce dynamic covalent hydrogels at physiological pH, we performed a molecular screening of PBA derivatives in association with a variety of diols, using hyaluronic acid as a polymer of interest. The combination of Wulff-type PBA (wPBA) and glucamine stood out as a unique couple to obtain the desired hydrogels. We showed that optimized wPBA/glucamine hydrogels are minimally- to non-swelling, stable long term (over months), tunable in terms of mechanical properties, and cytocompatible. We further characterized their viscoelastic and self-healing properties, highlighting their potential for biomedical applications.