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However, conventional injectable hydrogels release therapeutic factors in an uncontrolled manner, which leads to poor treatment efficacy and acute side effects on normal tissues. In\u00a0this\u00a0work, a matrix metalloproteinase (MMP)2\/9\u2010responsive hydrogel system (MPGC4) is developed, considering the characteristics of the post\u2010MI microenvironment. MPGC4 consists of tetra\u2010poly(ethylene glycol) (PEG) hydrogels and a composite gene nanocarrier (CTL4) that is composed of carbon dots (CDots) coupled with interleukin\u20104 plasmid DNA via electrostatic interactions. MPGC4 can be automatically triggered to release CTL4 on demand after MI to regulate the infarct immune microenvironment. In addition, due to the photoluminescence properties of CDots, a large amount of viscoelastic MPGC4 is found to be retained in situ after injection into the infarct region without leakage. The in vitro results demonstrate that CTL4 promotes proinflammatory M1 macrophage polarization to the anti\u2010inflammatory M2 subtype and contributes to cardiomyocyte survival through macrophage transition. In a rat model of MI, MPGC4 clears MMPs and precisely targets CTL4 to the infarcted region. In particular, MPGC4 improves cardiac function by modulating macrophage transition to reduce early inflammatory responses and proangiogenic activity.<\/jats:p>","DOI":"10.1002\/adma.202209041","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T20:15:45Z","timestamp":1675887345000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["A Matrix\u2010Metalloproteinase\u2010Responsive Hydrogel System for Modulating the Immune Microenvironment in Myocardial Infarction"],"prefix":"10.1002","volume":"35","author":[{"given":"Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  27 Taiping Rd Beijing 100850 P. R. 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