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.