Spatiotemporally reprogramming the cardiac pathological microenvironment with injectable POM-engineered hydrogel for chronological myocardial infarction treatment

The Fe-POM@gel is developed to chronological myocardial infarction treatment through spatiotemporally reprograming the cardiac pathological microenvironment. • The Fe-POM@gel sequentially exerts phase-specific functions-including oxygen generation, antioxidation, angiogenesis promotion, and immunomodulation-across the inflammatory, proliferative, and maturation phases of MI pathology. • This multifaceted reprogramming reverses infarct microenviroment, ultimately attenuating adverse ventricular remodeling and facilitating functional myocardial recovery. Myocardial infarction (MI) causes serious threats to people's lives due to its characteristic pathological microenvironment (PME) progression: inflammation, proliferation, and maturation phases. Nevertheless, traditional clinical therapies lack spatially targeted and temporally responsive modulation of the infarct microenvironment, resulting in limited myocardial repair effects. Fortunately, nanoenzyme-based engineered hydrogels show great potential in the regulation of the PME by spatiotemporally precise modulation, precise targeting, and on-demand feedback. Particularly, polyoxometalate (POM) nanozymes exhibit exceptional advantages for MI therapy including unique molecular structures, admirable redox properties and PME-sensitive aggregation properties. Thereby, an injectable POM-engineered hydrogel (Fe-POM@gel) with loading POM nanozyme into type I collagen and chondroitin sulfate (CS) is developed to chronological MI treatment through spatiotemporally reprograming the cardiac PME. During the inflammatory phase, Fe-POM@gel leverages its mixed valences of Fe 2+ /Fe 3+ and Mo 5+ /Mo 6+ to ameliorate oxidative stress and hypoxia through ROS-scavenging-driven cyclic H2O2/O 2 regeneration. In the proliferative phase, it promotes macrophage polarization and regulates inflammatory mediators, facilitating angiogenesis and tissue regeneration. In the maturation phase, Fe-POM@gel inhibits extracellular matrix (ECM) degradation and fibrosis progression, effectively preventing ventricular dilation and cardiac functional deterioration. Therefore, the Fe-POM@gel system provide a promising paradigm by spatiotemporally reprogramming strategy for MI chronological treatment. We developed an injectable Fe-POM@gel by loading polyoxometalate (POM) nanozyme into type I collagen and chondroitin sulfate (CS) for achieving chronological therapy of Myocardial infarction (MI) by spatially targeted and temporally adaptive regulation of pathological microenvironment (PME). Download: Download high-res image (170KB) Download: Download full-size image