Tough Injectable Hydrogels Enabled by Integrating Rigid Homogeneous Framework With Flexible Chains

ABSTRACT Injectable hydrogels hold significant promise for clinical applications because they enable minimally invasive administration and efficient in situ delivery of therapeutic agents. However, their weak mechanical properties substantially limit their practical use. Existing toughening strategies can enhance strength, but they often compromise biocompatibility or injectability. Here, we present a general strategy to enhance the toughness of single‐network (SN) injectable hydrogels by incorporating flexible polyethylene glycol (PEG) chains into a rigid hyaluronic acid (HA) framework, termed framework–flexible (FF) hydrogels. This design simultaneously increases network homogeneity and introduces chain‐length contrast for efficient energy dissipation. As a result, the optimized FF hydrogel achieves a 7‐fold increase in compressive strength and a 4‐fold increase in compressive toughness compared with its corresponding PEG‐free SN counterpart. In addition, the hydrogels exhibit excellent fatigue resistance and tunable mechanical properties while maintaining outstanding biocompatibility. This general approach provides a practical and powerful tool for developing tough, clinically compatible, and easily deployable injectable hydrogels.