Regulation of macrophage-mediated osteogenesis by kaempferol liposomes in trauma-induced heterotopic ossification.

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Heterotopic ossification (HO) is characterized by abnormal bone formation outside the skeleton following injury or inherited disease, leading to limb dysfunction and neurological deficits. Current treatment options for HO are largely ineffective. A network pharmacological analysis was conducted to identify the active ingredients and protein targets in Astragalus and Cinnamon Twig Five-Substance Decoction (ACTFSD) on HO. Protein-protein interaction analysis and Gene Ontology Enrichment Analysis were used to investigate the key genes associated with the target proteins. Molecular docking was employed to validate the interactions between the core components and targets of ACTFSD. Kaempferol was encapsulated in liposomes synthesized via the thin-film dispersion method. In vitro and in vivo experiments were conducted to evaluate the therapeutic effects of kaempferol liposomes. Kaempferol, an active ingredient in ACTFSD, effectively inhibits the PTGS2\ NF-κB pathway, regulates macrophage immune responses, and reduces cytokine released by macrophages induce abnormal osteogenesis in tendon stem cells (TDSCs), thereby slowing the formation of HO. Kaempferol liposomes demonstrate better therapeutic effect than kaempferol alone. This study indicates that targeting macrophages may represent an effective therapeutic strategy for HO. Furthermore, kaempferol liposomes appear to be a promising treatment for trauma-induced HO. These findings provide potential new directions for future HO treatment strategies.