Orchestrated Adhesive Anisotropic/Anti‐Adhesive Isotropic Janus Conductive Patch Reverses Ventricular Remodeling via Synchronized Electrophysiological Reconstitution and Mitochondrial‐Targeted Salvage

Abstract To overcome the limitations of current cardiac patches in comprehensively treating post‐infarction ventricular remodeling, a paradigm‐shifting orchestrated adhesive anisotropic/anti‐adhesive isotropic Janus conductive patch (AGMM/PDP) integrated with mitochondria‐targeted nanoparticles (MSNs/P/M) is introduced. The anisotropic AGMM layer enables suture‐free tissue integration via covalent/non‐covalent bonding, while the PDP layer forms a superhydrophilic antifouling barrier preventing postoperative adhesions. Simultaneously, MSNs/P/M nanoparticles achieve unprecedented mitochondrial salvage, leveraging polydopamine homing and melatonin synergy for enhanced mitochondrial affinity and efficient lysosomal escape, effectively preserving ultrastructure, membrane potential, and restoring oxidative phosphorylation to increase ATP production 1.8‐fold under hypoxia. Therapeutically, this integrated system orchestrates synchronized multi‐scale repair: acutely scavenging reactive oxygen species (ROS) (94% reduction), subsequently driving M1‐to‐M2 macrophage polarization to mitigate inflammation and stimulate angiogenesis (4.4‐fold increased vascular density), and chronically restoring anisotropic conduction (55% increased velocity) and mechanical synchrony via transcriptomic reprogramming (upregulating energy/contractile genes; downregulating fibrosis/inflammation markers). This synergistically reversed ventricular remodeling in vivo, evidenced by 25% improved ejection fraction, 3.5‐fold reduced fibrosis, and suppressed arrhythmias, collectively establishing a transformative. The developed patch presents a comprehensive Janus therapeutic strategy by mimicking the structural anisotropy native cardiac tissue while conferring mechanical isotropy, by inhibiting fibrosis, by restoring bioenergetics, which more effectively promotes cardiac functional recovery.