High-purity magnesium screws modulate macrophage polarization during the tendon–bone healing process in the anterior cruciate ligament reconstruction rabbit model  

作　　者：PengFei Cheng ZhenJun Weng Musha Hamushan Weijie Cai Yubo Zhang Zun Ren Yunchu Sun XiaoNong Zhang Hao Shen Pei Han 

机构地区：[1]Department of Orthopedic Surgery,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Yishan Rd 600,Shanghai 200233,China [2]State Key Laboratory of Metal Matrix Composites,School of Materials Science and Engineering,Shanghai Jiao Tong University,Shanghai,200240,China [3]Suzhou Origin Medical Technology Co.Ltd,Suzhou,215513,China

出　　处：《Regenerative Biomaterials》2022年第1期900-916,共17页再生生物材料（英文版）

基　　金：sponsored by the National Natural Science Foundation of China(No.81702183,No.81974325);Shanghai Sailing Program(No.17YF1414100).

摘　　要：Magnesium(Mg)screws perform clinical potential in anterior cruciate ligament(ACL)reconstruction,and promote fibrocartilaginous entheses regeneration at the femoral entrance.We aim to prove that high-purity Magnesium(HP Mg)screws modulate macrophage polarization in fibrocartilage interface regeneration both in vitro and in vivo.HP Mg extracts performed good cytocompatibility and significantly promoted M2 macrophage polarization in the flow cytometry and ELISA assays.M2 macrophages stimulated fibrochondrocyte differentiation of cocultured hBMSCs,and HP Mg extracts had synergistic effect on the process.Then we applied HP Mg screws,with Ti screws as control,in the ACL reconstruction rabbit model.In the histological and immunofluorescence analysis,HP Mg screws inhibited M1 polarization at 2 weeks and highly promoted M2 polarization at 2 and 4 weeks at the tendon–bone interface.Furthermore,regeneration of fibrocartilaginous entheses,rather than the fibrovascular scar interface,was detected in the HP Mg group at 12 weeks.For further mechanism study via RNA-seq detection and WB assays,we found that AKT1 was highly activated in M2 polarization,and HP Mg could stimulate AKT1 expression,rather than AKT2,in the early phase of tendon–bone healing.Our study elucidated macrophage polarization during tendon–bone healing process and emphasized HP Mg on M2 polarization and fibrocartilage interface regeneration via the selective activation of AKT1 and PI3K/AKT pathway.

关 键 词：high-purity magnesium tendon-bone healing anterior cruciate ligament reconstruction macrophage polarization 

分 类 号：R68[医药卫生—骨科学]