Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), 320 Yueyang Road, Shanghai, China.
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.
Acta Biomater. 2018 Jan 15;66:81-92. doi: 10.1016/j.actbio.2017.08.044. Epub 2017 Aug 30.
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 β-tricalcium phosphate (β-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 β-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 β-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-κB 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.
Silicate 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.
由于其出色的成骨和血管生成能力，硅酸盐生物陶瓷被认为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阐明。宿主对植入物的免疫防御被证明会极大地影响成骨和新骨形成，但到目前为止，很少有研究关注硅酸盐生物陶瓷调节宿主免疫反应。在本研究中，我们使用两种代表性的硅酸盐生物陶瓷——钙镁橄榄石（AKT）和顽辉石（NAGEL）作为模型材料，研究其在体外和体内的炎症反应，并用β-磷酸三钙（β-TCP）生物陶瓷作为对照。结果发现，与β-TCP 相比，在 AKT 和 NAGEL 生物陶瓷上培养的小鼠巨噬细胞 RAW264.7 不仅活力和增殖能力较低，而且炎症细胞因子的分泌也显著减少。在体内，植入材料周围形成的异物巨细胞和纤维囊、巨噬细胞的浸润以及检测到的炎症细胞因子都明显低于β-TCP 对照组。此外，我们发现不仅是硅酸盐生物陶瓷释放的特定浓度的细胞外含硅离子产物，而且单独的 Si、Mg 和 Ca 离子通过抑制激活的炎症 MAPK 和 NF-κB 信号通路以及促进巨噬细胞的 caspase 依赖性凋亡，显示出抑制巨噬细胞炎症反应的活性。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与宿主之间的离子微环境来调节免疫反应，这可能为硅酸盐生物陶瓷在骨再生中的生物活性机制提供新的见解，并为骨组织工程中新型生物材料的设计提供有益的指导。
