Pseudocapacitive Charge-Driven Adhesive-Electrocoupling Hydrogels for Myocardial Infarction Repair via Interstitial Microenvironment Remodeling.

Abstract

Myocardial infarction (MI) creates a hostile microenvironment characterized by oxidative stress, inflammation, fibrosis, and electrical conduction block, posing a multifaceted challenge for tissue repair. To address this, we developed a multifunctional hydrogel (Gel-PDZC), through an artificial neural network (ANN)-guided optimization process, incorporating nanoparticles comprising a ZIF-8@CaO₂ core for sustained oxygen release, a polydopamine (PDA) interlayer for adhesion and antioxidant activity, and a conductive poly(3,4-ethylenedioxythiophene) (PEDOT) shell. The hydrogel exhibits a unique "adhesion-electrocoupling" effect, where robust tissue adhesion facilitates a pseudocapacitive charge injection mechanism. This not only enables active electrical intervention in the avascular scar but also leverages the endogenous myocardial electric field to restore the hydrogel's antioxidant properties. In a rat MI model, the Gel-PDZC hydrogel comprehensively remodeled the myocardial interstitial microenvironment. It alleviated hypoxia, reduced oxidative stress and apoptosis, suppressed pro-inflammatory C-C motif chemokine receptor 2 (CCR2⁺) macrophages recruitment and promoted electrical coupling between resident CCR2^- macrophages and cardiomyocytes (CMs), inhibited fibroblast-to-myofibroblast transition via the PI3K/AKT pathway, and stimulated angiogenesis. These coordinated cellular and molecular changes translated into substantial functional recovery, evidenced by restored epicardial electrical propagation, improved electromechanical coupling, and a significant increase in cardiac function. Our findings demonstrate that this ANN-optimized, adhesive-electrocoupling hydrogel provides a comprehensive and synergistic solution for repairing the infarcted heart.