Precision reactive species scavenging enabled by engineered manganese-doped bimetallic MOF for tailored stem cell fate regulation

Abstract

The development of highly efficient antioxidant nanomaterials is crucial for protecting stem cells from oxidative stress, a major challenge in advancing stem cell therapy and tissue regeneration. While most existing materials focus on scavenging reactive oxygen species (ROS), the often-overlooked contribution of reactive nitrogen species (RNS) further amplifies oxidative damage, limiting therapeutic efficacy. Here, we report a manganese-doped bimetallic metal–organic framework (MOF), Dex@(Mn, Zn)EZIF-8, with a hollow architecture designed for precise ROS/RNS scavenging and osteogenic regulation. This MOF is synthesized via a one-pot method, followed by tannic acid-assisted etching and Dex loading. The incorporation of Mn, a transition metal with tunable valence states, significantly enhances catalase-like activity for ROS degradation, while tannic acid etching introduces additional sites for RNS neutralization. By mitigating oxidative stress, Dex@(Mn, Zn)EZIF-8 preserves the viability and essential functions of bone mesenchymal stem cells, including adhesion, proliferation, and migration, while also promoting osteogenic differentiation. Furthermore, the sustained release of Dex amplifies osteogenesis, as evidenced by the upregulated expression of key markers such as alkaline phosphatase, osteopontin, and osteocalcin. This multifunctional biocatalyst effectively integrates precision oxidative stress regulation with osteogenic promotion, offering a powerful strategy for stem cell protection and regenerative medicine, particularly in oxidative microenvironments.