Click and bioorthogonal hyaluronic acid hydrogels as an ultra-tunable platform for the investigation of cell–material interactions

This study presents a new hyaluronic acid-based hydrogel platform synthesized via strain-promoted azide–alkyne cycloaddition (SPAAC) click chemistry, allowing independent tuning of biochemical and mechanical properties. The hydrogels form within minutes at polymer concentrations as low as 0.5% and stiffness ranging from 0.5 to 45 kPa while maintaining cytocompatibility and long-term stability. Encapsulated stem cells remained >95% viable, and HA-based hydrogels enhanced secretion of immunomodulatory cytokines compared to alginate controls.