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 

作者机构：Department of OrthopaedicsUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Department of Spine SurgeryThe First Affiliated Hospital of Xinjiang Medical UniversityUrumqi830054China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2022年第7卷第11期

页      面：425-438页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 08[工学] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 

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. 

主　　题：Nanotopographic PEEK hMSCs Small extracellular vesicles Osteogenesis 

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.