Abstract
Injury and apoptosis of cardiomyocytes (CMs) lead to the excessive accumulation of reactive oxygen species (ROS) within the infarcted region, which affects the viability of healthy CMs in the border zone and contributes to the progressive enlargement of the infarct area. The subsequent replacement of necrotic myocardium with fibrotic tissue disrupts normal electrophysiological conduction pathways. This study develops a multifunctional hydrogel, TAlg/PEDOT@PMOF, incorporating an integrated PEDOT@PMOF nanofiller designed to simultaneously scavenge ROS and restore electrical coupling following myocardial infarction (MI). The ROS-neutralizing capability of the nanofiller stems from the manganese porphyrin, which closely emulates the catalytically active site of native antioxidant enzymes. To increase electrical conductivity, the conductive polymer PEDOT is immobilized onto the MOF structure via a polydopamine (PDA) adhesion layer. Furthermore, the hydrogel network is functionalized with cell-adhesion peptides, enabling a synergistic enhancement of ROS clearance and electrical signal transmission by the nanofiller at both the cellular and tissue scales. This dual functionality is evidenced by improved cytoprotection under oxidative stress, enhanced calcium transient in cardiomyocytes, restoration of cardiac function, and reduced susceptibility to arrhythmia. These results establish an effective strategy for engineering an integrated enzyme-mimicking system and highlight a practical and innovative approach for future MI therapy.