Solvent-engineered hydrogels: A multiscale design framework for bone regeneration.

Solvent engineering enables control over hydrogel structure by directly regulating polymer conformation, interfacial interactions, and network dynamics. In this context, ionic liquids (ILs) and deep eutectic solvents (DESs) govern the interactions that define structure-property-function relationships across length scales. In bone-regenerative systems, this approach enables coupled control of mechanical behavior, viscoelasticity, processability, and biological response, including mineralization and immune regulation. However, these advantages are constrained by narrow formulation windows, structure-dependent cytotoxicity in IL-based systems, and limited in vivo validation of DES-based materials. Advancing solvent-engineered hydrogels requires moving beyond empirical optimization toward predictive, multiscale design integrating molecular understanding, and standardized evaluation protocols to enable reproducible and clinically translatable systems.