Harnessing bacterial extracellular vesicles for bone and cartilage organoids

Age‐related bone disorders, such as osteoporosis (OP) and osteoarthritis (OA), are commonly associated with bone loss, cartilage degeneration, and impaired joint function, creating a significant health burden. Bone and cartilage organoids have become promising 3D models because they can partially reproduce natural tissue structures, cell diversity, and extracellular matrix features. However, current organoid systems still rely on biomaterial scaffolds and growth factors, which limits their ability to model multicellular crosstalk. Bacterial extracellular vesicles (BEVs) are non‐replicative nanoscale vesicles released by bacteria and enriched with diverse bioactive molecules. Compared with mammalian EVs or recombinant growth factors, BEVs are attractive because they are genetically programmable, scalable, and low cost. In this review, we discuss how BEVs can be integrated with bone and cartilage organoids, focusing particularly on the biological mechanisms, engineering methods, translational applications, biosafety issues, standardization requirements, and delivery challenges of BEVs. BEVs‐enabled organoids may provide programmable and scalable platforms for skeletal disease modeling, patient‐specific drug screening, and regenerative therapy.