Zn/Sr dual ions-collagen co-assembly hydroxyapatite enhances bone regeneration through procedural osteo-immunomodulation and osteogenesis  

作　　者：Zhenyu Zhong Xiaodan Wu Yifan Wang Mengdie Li Yan Li XuLong Liu Xin Zhang Ziyang Lan Jianglin Wang Yingying Du Shengmin Zhang 

机构地区：[1]Advanced Biomaterials and Tissue Engineering Center,Huazhong University of Science and Technology,Wuhan,430074,China [2]Department of Biomedical Engineering,Huazhong University of Science and Technology,Wuhan,430074,China [3]Institute of Regulatory Science for Medical Devices,Huazhong University of Science and Technology,Wuhan,430074,China [4]Department of Biomedical Engineering,The University of Texas at Austin,Austin,TX,78712,USA

出　　处：《Bioactive Materials》2022年第4期195-206,共12页生物活性材料（英文）

基　　金：supported by National Key R&D Project(2018YFC1105701)of China;National Natural Science Foundation of China(31870960,81801850);the Fundamental Research Funds for the Central Universities,HUST(2019kfyXMBZ021,2020kfyXJJS115).

摘　　要：The immune microenvironment induced by biomaterials played vital roles in bone regeneration.Hydroxyapatite(HA)and its ion-substituted derivates represent a large class of core inorganic materials for bone tissue engineering.Although ion substitution was proved to be a potent way to grant HA more biological functions,few studies focused on the immunomodulatory properties of ion-doped HA.Herein,to explore the potential osteoimmunomodulatory effects of ion-doped HA,zinc and strontium co-assembled into HA through a collagen template biomimetic way(ZnSr-Col-HA)was successfully achieved.It was found that ZnSr-Col-HA could induce a favorable osteo-immune microenvironment by stimulating macrophages.Furthermore,ZnSr-Col-HA demonstrated a procedural promoting effect on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.Specifically,the osteo-immune microenvironment acted as a dominant factor in promoting osteogenic gene expressions at the early stage through OSM signal pathway.Whereas the direct stimulating effects on BMSCs by Zn^(2+)/Sr^(2+) were more effectively at the later stage with Nfatc1/Maf and Wnt signals activated.In vivo study confirmed strong promoting effects of ZnSr-Col-HA on critical-sized cranial defect repair.The current study indicated that such a combined biomaterial design philosophy of dual ion-doping and biomimetic molecular co-assembly to endow HA applicable osteoimmunomodulatory characteristics might bring up a new cutting-edge concept for bone regeneration study.

关 键 词：HYDROXYAPATITE Zinc Strontium Biomimetic co-assembly Osteoimmunomodulation 

分 类 号：R318[医药卫生—生物医学工程] R68[医药卫生—基础医学]