Intelligent responsive PVA hydrogel loaded with composite MXene nanozyme enables efficient myocardial infarction repair by disrupting the oxidative stress-inflammation cascade.

Myocardial infarction (MI) is often accompanied by irreversible cardiomyocyte damage and limited tissue regeneration, posing a persistent challenge in clinical practice. In the early phase of MI, a burst of reactive oxygen species (ROS) and the resulting pro-inflammatory feedback loop lead to disruption of the myocardial microenvironment, immune dysregulation, and ultimately, impaired repair. Therefore, early clearance of ROS, inhibition of pro-inflammatory responses, and immune modulation toward a reparative phenotype are essential for effective intervention.To address this, we developed an intelligent, stimuli-responsive polyvinyl alcohol (PVA)-based hydrogel incorporating multifunctional MXene nanozymes for the localized and controllable delivery of 4-octyl itaconate (4-OI) to infarcted cardiac tissue. This system exhibits excellent fluidity, injectability, and in situ forming ability, enabling stable encapsulation and controlled release of 4-OI@MXene. Moreover, the mild reductive activity of MXene contributes to the creation of a more favorable microenvironment for tissue repair.Mechanistically, the hydrogel system activates the AMPK-Nrf2-Keap1 signaling axis to efficiently scavenge excessive ROS, while simultaneously suppressing NF-κB-mediated inflammation and promoting macrophage polarization toward the M2 phenotype. These coordinated effects substantially improve the oxidative and immune microenvironment post-MI, thereby facilitating myocardial repair and functional recovery.To our knowledge, this is the first study n the context of myocardial infarction to propose a synergistic activation of AMPK and Nrf2 signaling within a 4-OI@MXene-PVA hydrogel platform, offering a promising strategy for precise intervention and regenerative therapy following MI.