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Chiral self\u2010assemblies are one of the most ubiquitous life cues, which is closely related to biological functions, life processes, and even the pathogenesis of diseases. However, the role of supramolecular chiral self\u2010assemblies in the regulation of immune functions in the internal environment of tissues has not been fully explored yet. Herein, 3D supramolecular chiral self\u2010assembling matrixes are prepared to regulate the polarization of macrophages and further enhance the repair of myocardial infarction (MI). Experiments studies show that <jats:italic>M<\/jats:italic>\u2010type (left\u2010handed) self\u2010assembling matrixes significantly inhibit inflammation and promote damaged myocardium repair by upregulating M2 macrophage polarization and downstream immune signaling compared with <jats:italic>P<\/jats:italic>\u2010type (right\u2010handed), and <jats:italic>R<\/jats:italic>\u2010type (non\u2010chirality) self\u2010assembling matrixes. Classical molecular dynamics (MD) simulation demonstrates that <jats:italic>M<\/jats:italic>\u2010type self\u2010assembling matrixes display higher stereo\u2010affinity to cellular binding, which enhances the clustering of mechanosensitive integrin \u03b21 (Itg\u03b21) and activates focal adhesion kinase (FAK) and Rho\u2010associated protein kinase (ROCK), as well as downstream PI3K\/Akt1\/mTOR signaling axes to promote M2 polarization. This study of designing a 3D chiral self\u2010assembling matrixes microenvironment suitable for regulating the polarization of macrophages will provide devise basis for immunotherapy with biomimetic materials.<\/jats:p>","DOI":"10.1002\/advs.202304627","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T07:46:52Z","timestamp":1695887212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["3D Chiral Self\u2010Assembling Matrixes for Regulating Polarization of Macrophages and Enhance Repair of Myocardial Infarction"],"prefix":"10.1002","volume":"10","author":[{"given":"Lei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Renji Hospital School of Medicine Shanghai Jiao Tong University  160 Pujian Road Shanghai 200127 P. R. 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