骨免疫调节特性骨组织工程支架在修复骨缺损中的应用和发展  

Application and development of bone tissue engineering scaffolds with bone immune regulatory properties in repairing bone defects

作　　者：周宇翔 沈烈军 万诗雨 柴璐渝 逄人奇 李登顺 王鑫[5] 李展振 Zhou Yuxiang;Shen Liejun;Wan Shiyu;Chai Luyu;Pang Renqi;Li Dengshun;Wang Xin;Li Zhanzhen(Jiangxi University of Chinese Medicine,Nanchang 330004,Jiangxi Province,China;Zhoushan Dinghai Guanghua Hospital,Zhoushan 316000,Zhejiang Province,China;Guangzhou University of Chinese Medicine,Guangzhou 511400,Guangdong Province,China;College of Science and Technology,Jiangxi University of Chinese Medicine,Nanchang 330004,Jiangxi Province,China;Chinese PLA General Hospital,Beijing 100028,China)

机构地区：[1]江西中医药大学,江西省南昌市330004 [2]舟山定海广华医院,浙江省舟山市316000 [3]广州中医药大学,广东省广州市511400 [4]江西中医药大学科技学院,江西省南昌市330004 [5]解放军总医院,北京市100028

出　　处：《中国组织工程研究》2024年第29期4734-4740,共7页Chinese Journal of Tissue Engineering Research

基　　金：浙江省卫生健康科技计划(2022KY1372),项目负责人:沈烈军;舟山市医药卫生科技计划(2022YA16),项目负责人:沈烈军。

摘　　要：背景:在使用骨支架修复骨缺损时,注意骨免疫反应的调节对骨再生具有重要意义。目的:综述骨免疫反应对骨修复的影响和具有调节骨免疫功能的骨组织工程支架的设计和其在骨修复中的应用。方法:从Science Direct、PubMed、Web of Science与中国知网数据库中检索1973-2023年发表的相关文献。英文检索词:“Osteoimmunology,Macrophages,Bone repair materials,Bone scaffold,Bone defects,Bone regeneration”;中文检索词:“骨免疫,巨噬细胞,骨修复材料,骨支架,骨缺损,骨再生”,对筛选出该领域最新研究进展的80篇文献进行归纳分析。结果与结论:①文章详细梳理了骨免疫的起源和发展进程中的重要时间点,并阐述了巨噬细胞作为骨免疫调控体系中重要成员,可分为M1(促炎)和M2(抗炎)两类表型,并在骨再生的不同时期发挥着关键作用。在炎症期,M1型巨噬细胞一方面能激活破骨细胞,启动组织修复进程,同时参与骨内微血管网的重建,另一方面炎症后期的骨组织再生过程中,持续高表达M1型巨噬细胞会阻碍新骨形成;而在修复期,M2型巨噬细胞一方面可分泌成骨细胞因子,刺激骨髓间充质干细胞的成骨分化和矿化,进而促进骨形成,另一方面,长期激活的M2型巨噬细胞会增加促纤维化分子的分泌,导致瘢痕组织的过度形成,从而延迟愈合过程。因此调控巨噬细胞在适宜的阶段进行表型转换,构建有益于成骨的免疫微环境对骨再生意义巨大。②在设计具备骨免疫调控特性的骨支架过程中,可通过改变支架粗糙度、孔隙结构、刚度、亲水性、表面电荷、表面官能团等理化性质影响非特异性蛋白质和细胞黏附,从而影响骨支架与免疫系统的相互作用。而将羟基磷灰石,生物活性玻璃、金属离子、细胞外基质、药物、细胞因子和外泌体等生物活性物质进行表面功能涂层设计,则可在植入机体之后通过释放生物活性�BACKGROUND:Careful regulation of bone immune response during repair of bone scaffold is important for bone regeneration.OBJECTIVE:To review the influence of bone immune response on bone repair and the design of bone tissue engineering scaffold with regulating bone immune function and its application in bone repair.METHODS:Relevant articles published from 1973 to 2023 were retrieved from Science Direct,PubMed,Web of Science,and CNKI databases.English search terms were“osteoimmunology,macrophages,bone repair materials,bone scaffold,bone defects,bone regeneration”.Chinese search terms were“bone immunity,macrophages,bone repair material,bone stent,bone defect,bone regeneration”.Totally 80 articles of the latest research progress in this field were summarized and analyzed.RESULTS AND CONCLUSION:(1)A detailed review was conducted on the important time points in the origin and development process of bone immunity,and it was explained that macrophages,as important members of the bone immune regulatory system,can be divided into two phenotypes:M1(pro-inflammatory)and M2(anti-inflammatory),and play a key role in different stages of bone regeneration.During the inflammatory phase,M1 type macrophages can activate osteoclasts,initiate tissue repair processes,and participate in the reconstruction of bone microvascular networks.On the other hand,during the bone tissue regeneration process in the later stages of inflammation,sustained high expression of M1 type macrophages can hinder the formation of new bones.During the repair phase,M2 macrophages can secrete osteogenic cytokines,stimulate osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells,and promote bone formation.On the other hand,long-term activation of M2 macrophages can increase the secretion of fibrogenic molecules,leading to excessive formation of scar tissue and delaying the healing process.Therefore,regulating macrophages to undergo phenotype transformation at appropriate stages and constructing an immune microenvironment benef

关 键 词：骨免疫 免疫系统 骨骼系统 巨噬细胞 成骨细胞 破骨细胞 骨修复材料 骨支架 骨缺损 骨重建 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364