A functional cardiac patch promotes cardiac repair by modulating the CCR2- cardiac-resident macrophage niche and their cell crosstalk.

C-C chemokine receptor type 2 (CCR2-) cardiac-resident macrophages (CCR2- cRMs) are known to promote cardiac repair after myocardial infarction (MI). However, the substantial depletion and slow recovery of CCR2- cRMs pose significant barriers in cardiac recovery. Here, we construct a functional conductive cardiac patch (CCP) that can provide exogenously elastic conductive microenvironment and induce endogenously reparative microenvironment mediated by CCR2- cRMs for MI repair. This CCP exhibits suitable mechanical properties, conductivity, and high water retention, reminiscent of natural myocardium, which can actively engage in modulating CCR2- cRM renewal and their cell crosstalk. The functional CCP can promote the expression of Connexin43 between CCR2- cRMs and cardiomyocytes (CMs) and regulate paracrine signaling to activate epicardial cell epithelial-to-mesenchymal transition (EMT) toward endothelial cells using rat and Wt1CreERT2 transgenic lineage tracing mice. Overall, this study provides a promising strategy to construct a synergistic reparative microenvironment for MI repair.