Osteoporosis (OP) regenerative therapy remains challenging due to severe bone microenvironment dysregulation. Prussian blue (PB) is limited to acute diseases for its transient reactive oxygen species (ROS)-clearing effect, while manganese (Mn) exhibits potent antioxidant activity but poor biocompatibility. Herein, we synthesized a novel composite nanoparticle PB-Mn to address these limitations. In vitro experiments showed that PB-Mn efficiently scavenges ROS (H2O2, O2 -, •OH) in a dose-dependent manner, enhances antioxidant enzyme (CAT, SOD, POD, GPX) activities, and promotes M1-to-M2 macrophage polarization by reducing pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and increasing anti-inflammatory factors (IL-4, IL-10). In vivo studies using ovariectomized (OVX) mice confirmed that PB-Mn significantly increases bone mineral density (BMD), improves trabecular structure (trabecular volume fraction, thickness, and surface area), and balances osteoblast-osteoclast activities by alleviating oxidative stress and inflammation. This synergistic nanoplatform (PB for biocompatibility, Mn for enhanced ROS-scavenging) provides a novel strategy for osteoporosis treatment by targeting ROS and immune reprogramming.
Dai et al. (Fri,) studied this question.