A novel delivery nanobiotechnology: engineered miR-181b exosomes improved osteointegration by regulating macrophage polarization

Journal of Nanobiotechnology

Muyu Yu¹  Feng Chen²  Mingzhe Shao³  Cheng Ye⁴  Qing Chen⁴  Longqing Wang⁴  Wei Liu⁴  Dong Xie⁴  Qi Zhu⁴  Lili Yang⁴ 

[1] Department of Endocrinology and Metabolism, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Medical Centre of Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Clinic Centre of Metabolism Disease, Shanghai Institute for Diabetes, Shanghai, China;Department of Orthopaedics, Shanghai Fengxian Central Hospital, Branch of the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, 201400, Shanghai, People’s Republic of China;College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 200240, Shanghai, China;Department of Vascular Surgery, Multidisciplinary Collaboration Group of Diabetic Foot, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China;Spine Center, Department of Orthopaedics, Shanghai Changzheng Hospital, Second Affiliated Hospital of Naval Medical University, 200003, Shanghai, China;

关键词: Engineered;    Exosome;    Macrophage polarization;    MiR-181b;    Osteointegration;    Inflammation;   

DOI  :  10.1186/s12951-021-01015-y

来源: Springer

【 摘 要 】

BackgroundMany patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit the following osteogenesis, which could possibly give rise to aseptic loosening and poor osteointegration while there is currently no appropriate solution in clinical practice. Exosome (Exo) carrying miRNA has been proven to be a suitable nanocarrier for solving this problem. In this study, we explored whether exosomes overexpressing miR-181b (Exo-181b) could exert beneficial effect on promoting M2 macrophage polarization, thus inhibiting inflammation as well as promoting osteogenesis and elaborated the underlying mechanism in vitro. Furthermore, we aimed to find whether Exo-181b could enhance osteointegration.ResultsIn vitro, we firstly verified that Exo-181b significantly enhanced M2 polarization and inhibited inflammation by suppressing PRKCD and activating p-AKT. Then, in vivo, we verified that Exo-181b enhanced M2 polarization, reduced the inflammatory response and enhanced osteointegration. Also, we verified that the enhanced M2 polarization could indirectly promote the migration and osteogenic differentiation by secreting VEGF and BMP-2 in vitro.ConclusionsExo-181b could suppress inflammatory response by promoting M2 polarization via activating PRKCD/AKT signaling pathway, which further promoting osteogenesis in vitro and promote osteointegration in vivo.Graphic abstract

【 授权许可】

CC BY