Injectable Spiky Artificial Peroxidase‐Encapsulated Hydrogels for Bioadaptively and Synergistically Combating Endometrial Infections

Abstract Endometrial infections can lead to acute endometritis and persistent inflammation of the uterus, which may further lead to infertility in severe cases. It is a great challenge to develop a localized antimicrobial therapeutic strategy that exploits the infected microenvironment for effectively combating endometrial infections and facilitating endometrial repair. Here, an injectable spiky artificial Cu‐polyphthalocyanine peroxidase‐encapsulated thermosensitive hydrogel is engineered for bioadaptively and synergistically combating endometrial infection. The comprehensive investigations have elucidated that the Cu‐polyphthalocyanine network‐based spike‐linked enzyme‐mimics (SLE‐CuPPc) possess dual functionalities in combating endometrial infection. The spiky nanostructure enables efficient localized capture and kill action to bacteria and simultaneously generates a substantial quantity of reactive oxygen species (ROS). The attachment of SLE‐CuPPc to bacterial surfaces constricts the ROS action radius, thereby potentiating its bactericidal efficacy. SLE‐CuPPc is further encapsulated into a clinically approved thermosensitive hydrogel, yielding an injectable composite hydrogel, G‐SLE‐CuPPc. The endometrial infection models demonstrate that this composite hydrogel formulation not only eradicates S. aureus effectively but also stimulates vascular proliferation, curbs fibrosis, and fosters endometrial repair. This work demonstrates the pivotal role of G‐SLE‐CuPPc in eradicating antibiotic‐resistant bacteria and paves the way for developing next‐generation therapeutic hydrogels for clinical endometrial infection treatment.