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Figure 11. Both natural and engineered BEVs are promising therapeutic agents for OA therapy. BEVs play a crucial role in the gut-bone axis communication. Therefore, besides using these bacteria directly to alleviate OA, utilizing EVs derived from these bacteria may offer a superior treatment option. Additionally, both engineered strains and BEVs can be used to produce functional BEVs. These engineered BEVs exhibit enhanced properties, including reduced toxicity, high yield, targeted delivery to chondrocytes, and improved cartilage repair capabilities, thus providing greater potential for OA treatment. Created in BioRender. Bigbone B. (2025) https://BioRender.com/cw92itq. BEVs: Bacterial extracellular vesicles; OA: osteoarthritis; EVs: extracellular vesicles.