巨噬细胞及其特异性调控在生物材料纤维化形成中的作用  

Role and regulation of macrophages in biomaterial-mediated fibrosis formation

作　　者：邓墨渊 彭坤[1] Deng Moyuan;Peng Kun(Chongqing Medical and Pharmaceutical College,Chongqing 401331,China;National&Regional United Engineering Lab of Tissue Engineering,Department of Orthopaedics,Southwest Hospital,the Third Military Medical University,Chongqing 400038,China;Chongqing Forwos Medical Equipment Co.,Ltd.,Chongqing 400714,China)

机构地区：[1]重庆医药高等专科学校,重庆市401331 [2]中国人民解放军陆军军医大学第一附属医院骨科,组织工程国家地方联合工程实验室,重庆市400038 [3]重庆富沃思医疗器械有限公司,重庆市400714

出　　处：《中国组织工程研究》2023年第25期4085-4092,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81771995),项目负责人:邓墨渊;重庆市自然科学基金(cstc2018jcyjAX0828),项目负责人:彭坤。

摘　　要：背景:生物材料植入体内后引发的异物反应会导致其表面纤维化形成(又称为植入物纤维化),即生物材料被纤维组织包裹、使其丧失功能性、产生严重的临床并发症,是组织再生修复领域的一大难题。参与并调控植入物纤维化的关键细胞是巨噬细胞,但巨噬细胞对植入物纤维化进程的影响、机制及抑制纤维化的策略仍然不明确。目的:重点探讨巨噬细胞的极化和分化事件对材料纤维化的影响,包含促纤维化的信号通路,以及基于对巨噬细胞的特异性调控以抑制生物材料纤维化的策略。方法:应用计算机在PubMed,Wiley,EBSCOhost,ScienceDirect和Elsevier数据库检索截至2022年的相关文献,以“Macrophages,Biological materials,Fibrosis,Foreign body reaction,Myofibroblasts,Inflammation,Regulation,Surface topology,Mechanical properties,Chemical signals”为英文检索词,最终纳入60篇文献进行分析。结果与结论:①M1型和M2型巨噬细胞均可能参与生物材料纤维化形成,仅调节巨噬细胞极性的策略并不一定能抑制生物材料纤维化形成。②作为调控巨噬细胞介导生物材料纤维化的关键细胞事件,巨噬细胞向肌成纤维细胞的分化过程可以引起α-平滑肌肌动蛋标志物表达,显示该过程对纤维化有直接作用。③在巨噬细胞促纤维化的信号通路方面,分析认为不同表型的巨噬细胞其纤维化信号通路有可能存在差异。④在利用生物材料物理学特性调控巨噬细胞引起的炎症表达方面,主要有两个作用路径:一是从生物材料表面拓扑学的角度看,构建小于100 nm的图案表面,或者强化生物材料表面粗糙程度,有望实现降低巨噬细胞融合或表达炎性因子,减少巨噬细胞引起的纤维化;二是研究者可以更倾向于设计并制备具有较小弹性模量的生物材料,从而降低因植入物对损伤组织的应力传导,减少因巨噬细胞聚集后而引起的炎性因子表达,改善组BACKGROUND:The foreign body reaction induced by implanted biomaterials leads to the formation of surface fibrosis(also known as implant fibrosis),that is,biomaterials are wrapped by fibrous tissue,making them lose their functionality and producing serious clinical complications,which is a major problem in the field of tissue regeneration and repair.The key cells involved in implant fibrosis are macrophages.However,the effects and mechanism of macrophages on the process of implant fibrosis and the strategy of inhibiting fibrosis remain unclear.OBJECTIVE:To review the effects of macrophage polarization and differentiation events on material fibrosis,including fibrogenic signal pathways,and strategies to inhibit biomaterial fibrosis based on specific regulation of macrophages.METHODS:The relevant articles up to 2022 were searched on PubMed,Wiley,EBSCOhost,ScienceDirect,and Elsevier databases using English search terms"macrophages,biological materials,fibrosis,foreign body reaction,myofibroblasts,inflammation,regulation,surface topology,mechanical properties,chemical signals",and 60 articles were finally included for the further analysis.RESULTS AND CONCLUSION:(1)Both M1 and M2 macrophages may participate in the formation of biomaterial fibrosis.Maybe strategies that regulate macrophage polarity alone cannot inhibit the formation of fibrosis in biomaterials.(2)As a key cellular event in the regulation of macrophage-mediated biomaterial fibrosis,the differentiation of macrophages into myofibroblasts can induce the expression of markerα-smooth muscle actin,indicating that this process has a direct effect on fibrosis.(3)In terms of the signaling pathway of macrophages promoting fibrosis,the analysis suggests that there may be differences in the signaling pathway of macrophages with different phenotypes.(4)Two main pathways are involved in the regulation of macrophage-induced inflammation using the physical properties of biomaterials.First,based on the biomate rial surfa ce topology,the construction of patterning surfac

关 键 词：巨噬细胞 生物材料 纤维化 异物反应 肌成纤维细胞 炎症 调控 表面拓扑学 力学性能 化学信号 

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