3D Chiral Self‐Assembling Matrixes for Regulating Polarization of Macrophages and Enhance Repair of Myocardial Infarction

Abstract The regulation of inflammatory response at the site of injury and macrophage immunotherapy is critical for tissue repair. Chiral self‐assemblies 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‐assemblies in the regulation of immune functions in the internal environment of tissues has not been fully explored yet. Herein, 3D supramolecular chiral self‐assembling matrixes are prepared to regulate the polarization of macrophages and further enhance the repair of myocardial infarction (MI). Experiments studies show that M‐type (left‐handed) self‐assembling matrixes significantly inhibit inflammation and promote damaged myocardium repair by upregulating M2 macrophage polarization and downstream immune signaling compared with P‐type (right‐handed), and R‐type (non‐chirality) self‐assembling matrixes. Classical molecular dynamics (MD) simulation demonstrates that M‐type self‐assembling matrixes display higher stereo‐affinity to cellular binding, which enhances the clustering of mechanosensitive integrin β1 (Itgβ1) and activates focal adhesion kinase (FAK) and Rho‐associated protein kinase (ROCK), as well as downstream PI3K/Akt1/mTOR signaling axes to promote M2 polarization. This study of designing a 3D chiral self‐assembling matrixes microenvironment suitable for regulating the polarization of macrophages will provide devise basis for immunotherapy with biomimetic materials.