Regulation of immune response by bioactive ions released from silicate bioceramics for bone regeneration
Regulation of immune response by bioactive ions released from silicate bioceramics for bone regeneration
复制标题
通过硅酸盐生物陶瓷释放的生物活性离子调节免疫反应以促进骨再生。
DOI：
10.1016/j.actbio.2017.08.044
复制
发表时间：
2018-01-15
影响因子：
9.7
通讯作者：
Dai, Kerong
中科院分区：
文献类型：
--
作者：
Huang, Yan;Wu, Chengtie;Dai, Kerong
硅酸盐生物陶瓷具有良好的成骨和血管生成能力，在骨科组织再生方面具有广阔的临床应用前景。然而，硅酸盐生物陶瓷刺激骨形成的机制尚未完全了解。宿主对种植体的免疫防御对骨形成和新骨形成有重要影响，但目前关于硅酸盐生物陶瓷对宿主免疫应答的研究较少。在本研究中，两种具有代表性的硅酸盐生物陶瓷，镁黄长石（AKT）和nagelschmidtite（内格尔）作为模型材料，在体外和体内研究炎症反应，和-磷酸三钙（-TCP）生物陶瓷作为对照。结果发现，在体外，在AKT和内格尔生物陶瓷上培养的小鼠巨噬细胞RAW 264.7不仅表现出较低的存活率和增殖，而且比在-TCP上培养的巨噬细胞的炎性细胞因子分泌显著减少。与-TCP对照组相比，AKT和内格尔生物陶瓷组体内异物巨细胞和纤维囊的形成、巨噬细胞的侵袭以及植入材料周围检测到的炎性细胞因子均低得多。硅酸盐生物陶瓷不仅释放出一定浓度的胞外含硅离子产物，而且单独的Si、Mg和Ca离子也显示出抑制巨噬细胞炎症反应的活性，其作用机制可能是通过抑制活化的炎症MAPK和NF-B信号通路，促进巨噬细胞caspase依赖性凋亡。总的来说，我们的研究表明硅酸盐生物陶瓷可以通过改变植入物和宿主之间的离子微环境来调节免疫反应，本论文的主要研究内容是：硅酸盐生物陶瓷在骨组织工程中的生物活性及其生物学机制，为设计新型骨组织工程生物材料提供了有益的指导。它们在骨形成方面的优良特性。然而，很少有研究涉及它们与宿主免疫防御的相互关系，已被证明对成骨有很大影响。本研究以镁黄长石和钠长石为代表性硅酸盐生物陶瓷，研究其体内外炎症反应，首次发现硅酸盐生物陶瓷释放的生物活性离子通过抑制炎症信号和激活巨噬细胞凋亡来调节巨噬细胞免疫反应。本研究的结果不仅可以加深对硅酸盐生物陶瓷成骨活性的认识，而且可以为设计和制造新的骨组织工程生物材料提供有益的指导。(C)2017 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Silicate bioceramics have been considered to possess a wide prospect of clinical application for orthopedic tissue regeneration due to their excellent osteogenesis and angiogenesis. However, the mechanism for silicate bioceramics stimulating bone formation is not fully understood. The host immune defense to implants is proved to greatly influence the osteogenesis and new bone formation, but up to now, few studies are focused on the silicate bioceramics modulated host immune responses. In our present study, two representative silicate bioceramics, akermanite (AKT) and nagelschmidtite (NAGEL) were used as model materials to investigate the inflammation responses in vitro and in vivo, and -tricalcium phosphate (-TCP) bioceramics were used as a control. It was found that the mouse macrophage cell RAW264.7 that cultured on AKT and NAGEL bioceramics displayed not only less viability and proliferation, but also a significant less inflammatory cytokine secretion than those on -TCP in vitro. The formation of foreign body giant cells and fibrous capsules, the invasion of macrophages, as well as the detected inflammatory cytokines around the implanted materials were much lower in both AKT and NAGEL bioceramic groups as compared with those in the -TCP controls in vivo. Furthermore, it was found that not just the certain concentration of extracellular Si-containing ionic products released from the silicate bioceramics, but also the separate Si, Mg and Ca ions revealed the activity to inhibit the macrophage inflammatory responses by the way of suppressing the activated inflammatory MAPK and NF-B signaling pathway and promoting the caspase-dependent apoptosis of macrophages. In general, our study suggests that the silicate bioceramics could regulate immune responses by altering the ionic microenvironment between the implants and hosts, which may offer new insight about the mechanism of the bioactivity of silicate bioceramics in bone regeneration and provide profitable guidance for designing new biomaterials for bone tissue engineering.Statement of SignificanceSilicate bioceramics have been widely used for orthopedic tissue regeneration because of their excellent characteristics in bone formation. However, there are few studies concerning their interrelationships with the host immune defense that has been proved to greatly influence osteogenesis. In our present study, the akermanite and nagelschmidtite were used as two representative silicate bioceramics to investigate the inflammation responses in vitro and in vivo: and for the first time, the bioactive ions released from the silicate bioceramics were discovered to regulate the macrophage immune responses through both inhibiting the inflammatory signaling and activating apoptosis of macrophages. Our findings in this study may not only increase the understanding in osteogenic activity of silicate bioceramics, but also provide profitable guidance for designing and manufacturing new biomaterials for bone tissue engineering. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.