A pH/H₂O₂/MMP9 Time‐Response Gel System with Sparc^high Tregs Derived Extracellular Vesicles Promote Recovery After Acute Myocardial Infarction

Abstract

Regulatory T cells overexpressing SPARC (secreted protein acidic and cysteine rich) (Sparc^high Tregs) can help repair infarct tissues after acute myocardial infarction (AMI). This research demonstrates that Sparc^high Treg-derived extracellular vesicles (EVs) effectively improved cardiac function through proinflammatory factors IL-1β, IL-6, and TNF-α inhibition and collagen synthesis related gene Col3a1 promotion in AMI; moreover, a composite hydrogel-EVs system (DHPM(4APPC)_EVs) is designed based on Sparc^high Treg-derived EVs with CXCR2 overexpressing and pH/H₂ O₂ /MMP9 temporally responsive gel microspheres. In AMI, due to the levels of chemokine, pH, H₂ O₂ , and MMP9 enzymes in the infarct area, DHPM(4APPC)_EVs can effectively target the infarct area, release the loaded EVs, form the gel to capture the released EVs, and slowly release the captured EVs, contribute to promote EVs to stay in the infarct area for a long time to play the repair function, so as to reduce myocardial injury and promote the improvement of cardiac function. The proposed system in this research provides a potential approach for the treatment of AMI in the future.