A nanozyme-reinforced injectable photodynamic hydrogel for combating biofilm infection†

Bacterial biofilm-associated infectious diseases remain serious menaces to human health. Recently, photodynamic therapy (PDT) has become a prospective strategy for combating biofilm infection. However, anaerobic conditions in a biofilm greatly inhibit its therapeutic efficacy. Here, a nanozyme-reinforced injectable hydrogel is prepared using Ca²⁺-crosslinked sodium alginate incorporated with photosensitizer-loaded MnO₂ nanosheets and CaO₂ nanoparticles for O₂ self-sufficient PDT to eradicate biofilm infection. In our design, CaO₂ reacts with water to produce locally concentrated H₂O₂, which could be catalyzed by MnO₂ nanosheets (catalase-mimic nanozymes) to generate O₂ and greatly relieve the hypoxic conditions in the biofilm, thus significantly strengthening PDT efficacy. In vitro assays confirmed that the hybrid hydrogel not only exhibits high-performance bactericidal activity in combating both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli but also shows great efficacy in eliminating biofilm infection. Moreover, benefiting from its good syringeability, the hybrid hydrogel is prone to fit irregular wounds and exhibits high efficiency in promoting wound healing in a biofilm-infected mice model. Besides, no obvious toxicity is detected in the hybrid hydrogel. Overall, we envision that our designed hydrogel could provide a prospective solution for combating biofilm-associated infections.