Multifunctional manganese-based nanogels catalyze immune energy metabolism to promote bone repair

Abstract

Tissue regeneration during bone defect repair is regulated by the energy metabolism of macrophages. Abnormal energy metabolism can negatively affect bone repair in pathological conditions. A promising strategy involves developing biomaterials that regulate macrophage energy metabolism to coordinate immune response and bone regeneration. In this study, hollow mesoporous MnO₂, known for its excellent reactive oxygen species (ROS) scavenging and drug-loading abilities, was loaded with dexamethasone. This was followed by electrostatic self-assembly using chitosan coating to create nanogels (Alg-MD@CS). In vitro experiments showed that the nanogel effectively scavenged excess ROS, restored mitochondrial function, and reduced the levels of inflammatory factors. It downregulated glycolysis by inhibiting the ERK/HIF-1α/GLUT1 pathway, facilitating the M1-to-M2 phenotype switch to promote an anti-inflammatory and pro-regenerative ecological environment. In vivo experiments confirmed these findings. The nanogel reduced ROS levels in rats, reshaped the local immune microenvironment, and promoted bone regeneration. In summary, we developed a multifunctional nanogel for bone defect repair and demonstrated the significance and feasibility of reverse reprogramming by regulating the energy metabolism of macrophages during bone regeneration.