Dynamic Covalent Crosslinking Strategies for Tunable Hydrogel Networks

Dynamic covalent systems are interesting as they are composed of bonds which show covalent character, but become reversible under environmental stimuli such as temperature or pH [1,2]. Boronic acids in particular can bind with cis-1,2 or cis-1,3 diols to form into boronate esters, and this is affected by pH and other diols [3,4]. As a building block in supramolecular engineering, boronate crosslinks can be used to dynamically crosslink onto polymers to generate hydrogel networks with tunable states and properties.<br/><br/>Hydrogel printing has the contrasting needs of a highly processable and printable hydrogel, and a higher mechanical strength post deposition [5]. To expand the repertoire of materials suitable for hydrogel patterning, we report versatile polymer networks comprising of polyvinyl alcohol crosslinked with PEG-diboronates crosslinkers at low ratios [6]. These pre-gel networks are highly processable and extendable: they can be pulled up into thin strands and used for patterning of thin lines, and show shear thickening at higher shear rates. The pre-gels can be easily converted into a hydrogel state by pH adjustment and show clear antibacterial effects. Valuably, the pre-gels can be integrated into a 3D printing setup to print programmable lines and shapes and subsequently converted into patterned hydrogels.This study demonstrates that dynamic boronate networks can switch between a processable state and a mechanically stronger state and could offer alternate strategies and possibilities for hydrogel patterning applications.<br/><br/>Due to its relative stability and reprocessability, dynamic covalent crosslinking of supramolecular units onto polymer chains is an alternative way to fabricate supramolecularly crosslinked polymers.We functionalised the PVA polymer backbone with the carboxylate functionality through boronate crosslinking. This enabled the formation of a suprapolymeric conjugate with dynamically attached carboxylate moieties, which could subsequently form into supramolecular crosslinked hydrogels via ionic and electrostatic crosslinks. When crosslinked by calcium, a stronger hydrogel was formed which could not self-heal. When the polyelectrolyte branched polyethylenimine (PEI) was added, a stable hydrogel was formed with antibacterial properties.<br/><br/>In summary, we have shown that dynamic covalent boronate crosslinking can generate pH-switchable hydrogel states for printing applications or can be used to construct a suprapolymeric conjugate in combination with secondary supramolecular interactions. Dynamic covalent crosslinks can act as building blocks for the fabrication of functional yet responsive hydrogel materials.<br/><br/>References<br/>1. Chakma, P.; Konkolewicz, D., Dynamic Covalent Bonds in Polymeric Materials. Angewandte Chemie International Edition 2019, 58 (29), 9682-9695.<br/><u>2. Xue, K.</u>, Liow, S. S., ...., & Loh, X. J. (2018). A Recent Perspective on Noncovalently Formed Polymeric Hydrogels. The Chemical Record, 18(10), 1517-1529. doi:https://doi.org/10.1002/tcr.201800015<br/>3. Dong, Y., Wang, W., Veiseh, O., Appel, E. A., <u>Xue, K</u>.,. . . Anderson, D. G. (2016). Injectable and Glucose-Responsive Hydrogels Based on Boronic Acid–Glucose Complexation. Langmuir, 32(34), 8743-8747. doi:10.1021/acs.langmuir.5b04755<br/>4. Brooks, W. L. A., & Sumerlin, B. S. (2016). Synthesis and Applications of Boronic Acid-Containing Polymers: From Materials to Medicine. Chemical Reviews, 116(3), 1375-1397. doi:10.1021/acs.chemrev.5b00300<br/>5. Lee, S. C., et al. (2020). "Physical and Chemical Factors Influencing the Printability of Hydrogel-based Extrusion Bioinks." Chemical Reviews 120(19): 10834-10886.<br/>6. Tan, R., .., <u>Xue, K</u>.* (accepted). "Versatile and extendable boronate-based tunable hydrogel networks for patterning applications." DOI: https://doi.org/10.1021/acsapm.2c00614. *- corresponding author