Milk EVs Promote Apical Periodontitis Bone Repair via Osteoblast Targeting.

This article focuses on the development and evaluation of engineered milk-derived extracellular vesicles (MEVs) modified with the osteoblast-targeting peptide DSPE-PEG-Mal-Cys-SDSSD (DPS) for treating chronic apical periodontitis (CAP), an inflammatory bone disease. The DPS-modified MEVs (DPS-MEVs) demonstrated enhanced targeting to osteoblasts, promoted bone regeneration through activation of oxidative phosphorylation via Kruppel-like factor 4 (KLF4)-mediated upregulation of NADH dehydrogenase 1 alpha subcomplex 4 (Ndufa4), and modulated inflammation by promoting anti-inflammatory M2 macrophage polarization. In vivo studies using mouse skull defect and dog CAP models showed that DPS-MEVs improved bone repair and reduced inflammation more effectively than unmodified MEVs. These findings suggest that DPS-MEVs offer a dual-functional therapeutic strategy combining immunomodulation and tissue repair for precision treatment of inflammatory bone defects.