Accelerated Bone Regeneration by Gold-Nanoparticle-Loaded Mesoporous Silica through Stimulating Immunomodulation
Accelerated Bone Regeneration by Gold-Nanoparticle-Loaded Mesoporous Silica through Stimulating Immunomodulation
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DOI：
10.1021/acsami.9b16848
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发表时间：
2019-11-06
影响因子：
9.5
通讯作者：
Yang, Cao
中科院分区：
文献类型：
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作者：
Liang, Hang;Jin, Chen;Yang, Cao
局部免疫微环境对骨修复和再生的影响很大。因此，在评价生物材料的成骨作用时，应考虑其免疫调节能力。在这项研究中，我们研究了负载金纳米颗粒（AuNP）的介孔二氧化硅纳米颗粒（Au-MSNs）对巨噬细胞的调节作用以及随后对成骨细胞谱系行为的影响。结果表明，Au-MSNs可以通过刺激巨噬细胞的抗炎反应和促进成骨细胞因子的分泌来产生良好的免疫微环境。结果，成骨前MC3T3细胞的成骨分化增强，这可以通过成骨标志物、碱性磷酸酶（ALP）产生和钙沉积的表达增加来评估。在共培养系统中，au - msn调节的巨噬细胞与au - msn处理的成骨细胞之间产生串扰，从而协同提高MC3T3细胞的成骨分化能力。一项体内研究进一步显示，基于计算机断层扫描分析和组织学检查，Au-MSNs可以加速大鼠临界尺寸颅骨缺损部位的新骨形成。总之，这种新型au - msn可以通过调节免疫微环境显著促进成骨活性，显示出其在骨组织修复和再生方面的治疗潜力。
Bone repair and regeneration are greatly influenced by the local immune microenvironment. In this regard, the immunomodulatory capability of biomaterials should be considered when evaluating their osteogenic effects. In this study, we investigated the modulatory effects of gold nanoparticle (AuNP)-loaded mesoporous silica nanoparticles (Au-MSNs) on macrophages and the subsequent effects on the behavior of osteoblastic lineage cells. The results demonstrate that Au-MSNs could generate a favorable immune microenvironment by stimulating an anti-inflammatory response and promoting the secretion of osteogenic cytokines by macrophages. As a result, there is an enhancement of osteogenic differentiation in preosteoblastic MC3T3 cells as assessed by the increased expression of osteogenic markers, alkaline phosphatase (ALP) production, and calcium deposition. The immunomodulatory effects and direct osteogenic stimulation by Au-MSNs synergistically increased the osteogenic differentiation capability of MC3T3 cells as a result of crosstalk between Au-MSN-conditioned macrophages and Au-MSN-treated osteoblasts in a coculture system. An in vivo study further revealed that Au-MSNs could accelerate new bone formation in a critical-sized cranial defect site in rats based on computed tomography analysis and histological examination. Together, this novel Au-MSNs could significantly promote osteogenic activity by modulating the immune microenvironment, showing its therapeutic potential for bone tissue repair and regeneration.