A tripartite therapeutic agent reprograms the myocardial infarction microenvironment

Myocardial infarction (MI) remains a global health challenge despite advances in reperfusion therapies, as subsequent oxidative stress, inflammatory cascades, and electrical conduction abnormalities impede functional recovery. This study presents a tripartite therapeutic strategy addressing these pathological mechanisms through a clinically translatable multifunctional myocardial repair agent (MMRA). The system combines polypyrrole's and sinomenine's (Sino) anti-inflammatory/antioxidant effects, formulated within a conductive thermoresponsive Poloxamer 407 (P407) hydrogel platform. Injectable P407 hydrogel facilitates targeted delivery and sustained release of therapeutic components within the infarct zone. In vivo evaluations revealed MMRA's capacity to simultaneously: 1) Scavenge reactive oxygen species and downregulate pro-inflammatory cytokines, 2) Reprogram macrophage polarization toward tissue-reparative M2 phenotypes and 3) Restore electrical signal propagation through conductive hydrogel-mediated intercellular coupling. By synergistically modulating the post-infarction microenvironment while preserving myocardial electromechanical synchronization, this integrated therapeutic paradigm demonstrates significant potential for enhancing cardiac repair outcomes. The employment of clinically approved components (Sino and P407) further shows the excellent translational feasibility of the MMRA for MI treatment.