Accurately tuning the macroscopic properties of biopolymer‐based hydrogels remains challenging due to the ill‐defined molecular architecture of the natural building blocks. Here, we report a biohybrid coacervate hydrogel, combining the biocompatibility and biodegradability of naturally occurring hyaluronic acid (HA) with the tunability of a synthetic polyethylene oxide (PEO) ‐based ABA‐triblock copolymer. Coacervation of the cationic ammonium or guanidinium‐functionalized copolymer A‐blocks with the anionic HA leads to hydrogel formation. Both mechanical properties and water content of the self‐healing hydrogels can be controlled independently by altering the copolymer structure. By controlling the strength of the interaction between the polymer network and small‐molecule cargo, both release rate and maximum release are controlled. Finally, we show that coacervation of HA and the triblock copolymer leads to increased biostability upon exposure to hyaluronidase. We envision that noncovalent crosslinking of HA hydrogels through coacervation is an attractive strategy for the facile synthesis of tunable hydrogels for biomedical applications.
