Competitive ligand exchange of crosslinking ions for ionotropic hydrogel formation

Currently there are limitations to gelation strategies to form ionically crosslinked hydrogels, derived in particular from a lack of control over the release kinetics of crosslinking ions, which severely restrict applications. To address this challenge, we describe a new approach to form hydrogels of ionotropic polymers using competitive displacement of chelated ions, thus making specific ions available to induce interactions between polymer chains and form a hydrogel. This strategy enables control of ion release kinetics within an aqueous polymer solution and thus control over gelation kinetics across a wide range of pH. The described technique simplifies or facilitates the use of ionotropic hydrogels in a range of applications, such as 3D printing, microfluidic-based cell encapsulation, injectable preparations and large scale bubble and solid free mouldable gels. We investigate a range of chelator-ion combinations and demonstrate this powerful method to form hydrogels across a wide range of pH and μm-cm length scales. We highlight our findings by applying this gelation strategy to some of the more challenging hydrogel application areas using alginate and polygalacturonate as model polymer systems.