Pericardial Delivery of SDF-1α-encapsulated Puerarin Hydrogel Promotes Endogenous Repair and Electrical Coupling After Myocardial Infarction.

The SDF-1α/CXCR4 axis contributes to myocardial protection after MI by recruiting endogenous stem cells into the ischemic tissue. However, excessive inflammatory macrophages are also recruited simultaneously, aggravating myocardial damage. More seriously, the increased inflammation contributes to abnormal cardiomyocyte electrical coupling, leading to inhomogeneities in ventricular conduction and retarded conduction velocity. It is highly desirable to selectively recruit the stem cells but block the inflammation. In this work, the SDF-1α-encapsulated Puerarin (PUE) hydrogel (SDF-1α@PUE) that is capable of enhancing endogenous stem cell homing and simultaneously polarizing the recruited monocyte/macrophages into a repairing phenotype. Flow cytometry analysis of the treated heart tissue shows that endogenous bone marrow mesenchymal stem cells (BMSCs), hemopoietic stem cells (HSCs), and immune cells are recruited while SDF-1α@PUE efficiently polarized the recruited monocytes/macrophages into the M2 type. These macrophages influence the preservation of Cx43 expression which modulates intercellular coupling and improves electrical conduction. Furthermore, by taking advantage of the improved "soil", the recruited stem cells mediates an improved cardiac function by preventing deterioration, promoting neovascular architecture, and reducing infarct size. Our findings demonstrate a promising therapeutic platform for MI that not only facilitates heart regeneration but also reduces the risk of cardiac arrhythmias. This article is protected by copyright. All rights reserved.