Small extracellular vesicles with nanomorphology memory promote osteogenesis  

作　　者：Liang Ma Wencan Ke Zhiwei Liao Xiaobo Feng Jie Lei Kun Wang Bingjin Wang Gaocai Li Rongjin Luo Yunsong Shi Weifeng Zhang Yu Song Weibin Sheng Cao Yang 

机构地区：[1]Department of Orthopaedics,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China [2]Department of Spine Surgery,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,830054,China

出　　处：《Bioactive Materials》2022年第11期425-438,共14页生物活性材料（英文）

基　　金：This study was supported by the National Key R&D Program of China(2018YFB1105700);the National Natural Science Foundation of China(81902261,81772401);the Fundamental Research Funds for the Cen-tral Universities(2019kfyXMBZ063);the Application Foundation and Advanced Program of Wuhan Science and Technology Bureau(2019020701011457);We also thank the Medical Subcenter of HUST Analytical&Testing Center in data acquisition.

摘　　要：Nanotopographical cues endow biomaterials the ability to guide cell adhesion, proliferation, and differentiation. Cellular mechanical memory can maintain the cell status by retaining cellular information obtained from past mechanical microenvironments. Here, we propose a new concept “morphology memory of small extracellular vesicles (sEV)” for bone regeneration. We performed nanotopography on titanium plates through alkali and heat (Ti8) treatment to promote human mesenchymal stem cell (hMSC) differentiation. Next, we extracted the sEVs from the hMSC, which were cultured on the nanotopographical Ti plates for 21 days (Ti8-21-sEV). We demonstrated that Ti8-21-sEV had superior pro-osteogenesis ability in vitro and in vivo. RNA sequencing further confirmed that Ti8-21-sEV promote bone regeneration through osteogenic-related pathways, including the PI3K-AKT signaling pathway, MAPK signaling pathway, focal adhesion, and extracellular matrix-receptor interaction. Finally, we decorated the Ti8-21-sEV on a 3D printed porous polyetheretherketone scaffold. The femoral condyle defect model of rabbits was used to demonstrate that Ti8-21-sEV had the best bone ingrowth. In summary, our study demonstrated that the Ti8-21-sEV have memory function by copying the pro-osteogenesis information from the nanotopography. We expect that our study will encourage the discovery of other sEV with morphology memory for tissue regeneration.

关 键 词：Nanotopographic PEEK HMSCS Small extracellular vesicles OSTEOGENESIS 

分 类 号：R68[医药卫生—骨科学] R318[医药卫生—外科学]