Ionotropic gelation of polymers containing bisphosphonate groups crosslinked with divalent cations

Ionotropic hydrogels, formed through reversible coordination between multivalent metal ions and chelating ligands, represent a promising class of injectable biomaterials that allow for minimally invasive implantation in the body, the encapsulation of unstable biomolecules without loss of biological activity and the fabrication of well-defined three-dimensional objects via extrusion 3D printing. In this study, we report a novel ionotropically gelling polymer containing bisphosphonate groups. The polymers were synthesized from alendronate acrylamide via free radical polymerization. Upon the addition of Ca²⁺ and Zn²⁺ ions, the polymers formed hydrogels with tunable mechanical properties with higher polymer concentrations, resulting in stiffer hydrogels. Notably, hydrogels with a polymer concentration of 2.5 wt% exhibited a high shear storage modulus of approximately 140 kPa, indicating significant mechanical strength. The hydrogels showed self-healing and stress-thinning behaviors, which are typical of systems crosslinked via dynamic bonds. In addition, hydrogel nanoparticles were fabricated by crosslinking the polymers with Zn²⁺ ions within water-in-oil emulsions. These findings highlight bisphosphonate-bearing polymers as promising ionotropically gelling biomaterials for biomedical applications such as tissue engineering and drug delivery.