Multifaceted Catalytic ROS‐Scavenging via Electronic Modulated Metal Oxides for Regulating Stem Cell Fate

Developing reactive oxygen species (ROS)‐scavenging nanostructures to protect and regulate stem cells has emerged as an intriguing strategy for promoting tissue regeneration, especially in trauma microenvironments or refractory wounds. Here, an electronic modulated metal oxide is developed via Mn atom substitutions in Co3O4 nanocrystalline (Mn‐Co3O4) for highly efficient and multifaceted catalytic ROS‐scavenging to reverse the fates of mesenchymal stem cells (MSCs) in oxidative‐stress microenvironments. Benefiting from the atomic Mn‐substitution and charge transfer from Mn to Co, the Co site in Mn‐Co3O4 displays an increased ratio of Co2+/Co3+ and improved redox properties, thus enhancing its intrinsic and broad‐spectrum catalytic ROS‐scavenging activities, which surpasses most of the currently reported metal oxides. Consequently, the Mn‐Co3O4 can efficiently protect the MSCs from ROS attack and rescue their functions, including adhesion, spreading, proliferation, and osteogenic differentiation. This work not only establishes an efficient material for catalytic ROS‐scavenging in stem‐cell‐based therapeutics but also provides a new avenue to design biocatalytic metal oxides via modulation of electronic structure. An electronic modulated metal oxide via Mn‐atom substitutions in Co3O4 (Mn‐Co3O4) is synthesized for reactive oxygen species (ROS)‐scavenging and regulating stem cells fates. The experiments and theoretical calculations reveal that Mn‐Co3O4 displays excellent intrinsic and broad‐spectrum catalytic ROS‐scavenging activities, which can efficiently protect mesenchymal stem cells (hMSCs) from ROS attack, reverse the apoptotic fates, and rescue their functions in oxidative stress microenvironments.