Biological Cardiac Patch Based on Extracellular Vesicles and Extracellular Matrix for Regulating Injury-Related Microenvironment and Promoting Cardiac Tissue Recovery.

Cardiac patches are widely investigated to repair or regenerate diseased and aging cardiac tissues. While numerous studies looked into engineering the biochemical/biomechanical/cellular microenvironment and components in the heart tissue, the changes induced by cardiac patches and how they should be controlled to promote cardiac tissue repair/regeneration remains an important yet untapped direction, especially immunological responses. In this study, we designed and fabricated a bilaminated cardiac patch based on extracellular matrix (ECM) materials loaded with the extracellular vesicles (EVs) derived from mesenchymal stromal cells. The function of the biological material to modulate the injury-related microenvironment in a cardiac infarction model in mice was investigated. The study showed that the treatment of EV-ECM patches to the infarcted area increased the level of immunomodulatory major histocompatibility complex class II lo macrophages in the early stage of myocardial injury to mitigate excessive inflammatory responses due to injury. The intensity of the acquired proinflammatory immune response in systemic immune organs was reduced. Further analyses indicated that the EV-ECM patches exhibited proangiogenic functions and decreased the infarct size with improved cardiac recovery in mice. The study provided insights into shaping the injury-related microenvironment through the incorporation of extracellular vesicles into cardiac patches, and the EV-ECM material is a promising design paradigm to improve the function of cardiac patches to treat myocardial injuries and diseases.