Bone-targeted hybrid extracellular vesicles for alveolar bone regeneration

Anqi Liu; Gang Yang; Yijie Zhao; Jiajia Deng; Jialiang Liu; Kairun Zhang; Li Mei; Yan Liu; Tingjiao Liu

doi:10.1002/INMD.20240126

Interdisciplinary Medicine ›› 2025, Vol. 3 ›› Issue (3) :e20240126 DOI: 10.1002/INMD.20240126

RESEARCH ARTICLE

Bone-targeted hybrid extracellular vesicles for alveolar bone regeneration

Anqi Liu ¹^,²^,³
, Gang Yang ⁴^,⁵
, Yijie Zhao ⁵^,⁶
, Jiajia Deng ⁵^,⁷
, Jialiang Liu ⁵^,⁸
, Kairun Zhang ⁵^,⁷
, Li Mei ⁹
, Yan Liu ¹⁰
, Tingjiao Liu ⁵^,¹¹

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¹. Department of Orthodontics, School of Medicine, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China

². National Clinical Research Center for Oral Diseases, Beijing, China

³. Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China

⁴. Department of Multidisciplinary Consultant Center, Shanghai Stomatological Hospital & School of Stomatology, Shanghai, China

⁵. Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, China

⁶. Department of Periodontology, Shanghai Stomatological Hospital & School of Stomatology, Shanghai, China

⁷. Department of Orthodontics, Shanghai Stomatological Hospital & School of Stomatology, Shanghai, China

⁸. Department of Oral and Maxillofacial Surgery, Shanghai Stomatological Hospital & School of Stomatology, Shanghai, China

⁹. Department of Oral Sciences, Faculty of Dentistry, University of Otago, Dunedin, New Zealand

¹⁰. Central Laboratory, Peking University School and Hospital for Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China

¹¹. Department of Oral Pathology, Shanghai Stomatological Hospital & School of Stomatology, Shanghai, China

li.mei@otago.ac.nz

orthoyan@bjmu.edu.cn

tingjiao_liu@fudan.edu.cn

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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.

Keywords

alveolar bone defect / bone targeting / DNA nanostructures / hybrid EVs / liposomes

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Anqi Liu, Gang Yang, Yijie Zhao, Jiajia Deng, Jialiang Liu, Kairun Zhang, Li Mei, Yan Liu, Tingjiao Liu. Bone-targeted hybrid extracellular vesicles for alveolar bone regeneration. Interdisciplinary Medicine, 2025, 3(3): e20240126 DOI:10.1002/INMD.20240126

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