Ischemia-reperfusion (I/R) injury leads to a low success rate of skin flap transplantation in reconstruction surgery, thus requiring development of new treatments. Necroptosis and apoptosis pathways, along with overexpression of reactive oxygen species and pro-inflammatory factors in skin flap transplantation, are deemed as potential therapeutic targets. This study provides a paradigm for nanozyme-mediated microenvironment maintenance to improve the survival rate of the transplanted skin flap. Prussian blue nanozyme (PBzyme) with multiple intrinsic biological activities was constructed and selected for this proof-of-concept study. The prepared PBzyme shows anti-inflammatory, antiapoptotic, antinecroptotic, and antioxidant activities in both and models of I/R injured skin flaps. The multiple inhibitory effects of PBzyme maintained a normal microenvironment and thus significantly promoted the survival rate of the I/R injured skin flap (from 37.21 ± 8.205% to 79.61 ± 7.5%). Of note, PBzyme regulated the expression of the characteristic signal molecules of necroptosis, including Rip 1, Rip 3, and pMLKL, indicating that PBzyme may be a therapeutic agent for necroptosis-related diseases. This study shows great prospects for clinical application of PBzyme in the treatment of skin flaps local administration.
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