Bone-targeted hybrid extracellular vesicles for alveolar bone regeneration

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.