Ion-responsive alginate based macroporous injectable hydrogel scaffolds prepared by emulsion templating

Ion-responsive biocompatible macroporous hydrogels with a well-defined highly interconnected open porous structure were synthesised using oil-in-water (o/w) high internal phase emulsion (HIPE) templating. Methacrylate-modified alginate was crosslinked in the continuous minority water phase and the oil internal phase removed to produce macroporous hydrogel monoliths. The physical dimensions, pore and pore throat size as well as water uptake of the alginate polyHIPE hydrogel can be controllably tuned by ion-responsive behaviour towards Ca²⁺ ions. The ionic crosslinks formed are fully reversible and be dissolved using sodium citrate to remove Ca²⁺ ions through chelation. The polyHIPE hydrogels possess mechanical properties with storage moduli up to 20 kPa and are biocompatible as shown by cytotoxicity assays. The hydrogel can be extruded through a hypodermic needle causing it to break into small pieces (about 1 to 3 mm in diameter) while retaining the interconnected pore morphology after injection. Furthermore, these hydrogel fragments can be reformed into a coherent scaffold under mild conditions using an alginate solution containing Ca²⁺ ions.