Armor Inspired Biomimetic Mineralized Mn Nanozyme Armor Protects MSC Cell Sheets for Myocardial Infarction

ABSTRACT In early myocardial infarction, excessive ROS accumulation drives oxidative stress, inflammation, impaired angiogenesis, and ultimately results in fibrosis and ventricular remodeling. Although cell sheet therapy offers regenerative potential, its efficacy is limited by poor cell survival in the harsh microenvironment. Inspired by armor protection, we proposed a bionic mineralization method to coat stem cell sheets with nanozymes—a strategy rarely reported to date. Herein, we first developed a simple method to prepare cell sheets with enhanced cell proliferation and adhesion protein expression, including integrin α5β1. Innovatively, a pre‐mineralization transition layer composed of extracellular matrix components fibronectin (Fn) and gelatin (G) was formed on the sheet surface as mild and controllable pre‐mineralization transition layer, protecting stem cells from damage and differentiation. For the first time, manganese nanozymes with dual enzyme‐mimetic activities (CAT and SOD) were mineralized onto stem cell sheets, which could effectively eliminate ROS, reduce apoptosis and inflammatory response. Mechanistically, mineralized MSC promoted vascularization and synergistically improved myocardial repair by stabilizing HIF‐1α, ultimately improving cardiac function and attenuating ventricular remodeling. Collectively, this study provided an integrated strategy to enhance cell sheet therapy and expanded nanozyme applications in the field of cell therapy, holding promise for rapid clinical translation.