Bone‐targeted hybrid extracellular vesicles for alveolar bone regeneration

Abstract Prolonged tooth loss causes a blade‐like narrowing of the alveolar bone, severely impairing chewing function and aesthetics and complicating subsequent orthodontic or restorative treatments. Bone morphogenetic protein‐2 (BMP‐2) is widely used to induce osteogenesis; however, its lack of cellular targeting in complex microenvironments often results in significant side effects. Developing a safe, stable, and osteoblast‐targeted drug delivery system is crucial for precise bone regeneration. Nanoparticles, as ideal drug delivery vehicles, offer highly controllable cellular targeting. This study introduces an innovative approach using DNA nanostructure‐modified BMP‐2‐loaded hybrid extracellular vesicles (EVs) formed by fusing liposomes and EVs. Screening identified 180 nm as the optimal particle size for EVs fusion efficiency. The system achieved osteoblast‐specific targeting by attaching the DNA aptamer 19S to the hybrid EVs membrane. The hybrid EVs were further combined with a hydrogel sustained‐release system, creating a drug delivery platform that effectively repaired alveolar bone defects. This approach demonstrated significant potential for advancing bone tissue repair and regeneration.