Antibacterial Hydrogel Dressing With Ca 2+ ‐Dependent Hyaluronidase Responsiveness for Accelerating Wound Healing via On‐Demand Release of AIE Photosensitizers

ABSTRACT Reactive oxygen species (ROS)‐assisted photodynamic antibiosis emerges as an effective non‐antibiotic way to eradicate bacteria in infected wounds. To minimize the indiscriminate damage of excessive ROS to normal tissues, on‐demand release of photosensitizers (PSs) is highly desired. Herein, we report a novel aggregation‐induced emission (AIE) PSs‐loaded hydrogel wound dressing by incorporating AIE PSs into hydrogels prepared from sodium alginate and hyaluronic acid (HA) upon crosslinking in Ca 2+ solution. By virtue of the hyaluronidase (HAase) that is secreted from bacteria, AIE PSs can be released from hydrogels due to the HA degradation. Particularly, the HAase activity can be elevated in the presence of low concentrations of Ca 2+ , where HAase tends to adopt a more stable conformation, whereas high concentrations of Ca 2+ triggers the salt precipitation of HAase, thereby inhibiting its activity. Benefitting from this advantageous Ca 2+ ‐dependent HAase responsiveness, on‐demand release of AIE PSs regulated by the Ca 2+ that freely diffused from hydrogels is actualized, as evidenced by the accelerated healing of in vivo bacteria‐infected wounds. Overall, this work not only reports the bidirectional regulation mode of Ca 2+ on HAase activity and elucidates the mechanism for the first time, but also provides a new strategy with on‐demand release of antibacterial PSs for accelerated wound healing.