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Antioxidant mesoporous Ce-doped bioactive glass nanoparticles with anti-inflammatory and pro-osteogenic activities
Materials Today Bio ( IF 8.7 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.mtbio.2020.100041
Kai Zheng , Elisa Torre , Alessandra Bari , Nicola Taccardi , Clara Cassinelli , Marco Morra , Sonia Fiorilli , Chiara Vitale-Brovarone , Giorgio Iviglia , Aldo R. Boccaccini

Mesoporous bioactive glass nanoparticles (MBGNs) are emerging biomaterials for bone repair/regeneration, considering their favorable pro-osteogenic and proangiogenic activities. To further improve their therapeutic effects, the endowment of MBGNs with additional antioxidant properties is of particular interest to target oxidative stress related to bone remodeling and diseases. To this end, we developed antioxidant cerium-containing MBGNs (Ce-MBGNs) (particle size of 100–300 ​nm) by using a postimpregnation strategy to incorporate Ce, through which the shape, pore structure, and dispersity of the nanoparticles were preserved. The incorporated amount of Ce could be tailored by adjusting the concentration of the Ce precursor solution. When impregnated at a relatively low temperature (20 ​°C), Ce-MBGNs containing either 1.8 or 2.8 ​mol% of Ce were produced, while the formation of by-product cerium oxide nanoparticles (nanoceria) could be avoided. In both developed Ce-MBGNs, the concentration of Ce4+ was higher than that of Ce3+, while the relative molar percentage of Ce4+ was similar (∼74%) in both Ce-MBGNs. The obtained Ce-MBGNs were evidenced to be non-cytotoxic against fibroblasts at the concentration of 1 ​mg/mL. Moreover, the incorporation of Ce into MBGNs significantly reduced the expression of oxidative stress–related genes in macrophages (J774a.1). Particularly in the presence of pro-oxidation agents, Ce-MBGNs could downregulate the expression of oxidative stress–related genes in comparsion with the polystyrene plates (control). When cultured with Ce-MBGNs, the expression of proinflammatory-related genes in macrophages could also be downregulated in comparsion with MBGNs and the control. Ce-MBGNs also exhibited pro-osteogenic activities through suppressing pro-osteoclastogenic responses. The obtained results highlight the great potential of the developed Ce-MBGNs in a variety of biomedical applications, particularly in treating bone defects under inflammatory conditions, considering their antioxidant, anti-inflammatory, and pro-osteogenesis activities.



中文翻译:

具有抗炎和促成骨活性的抗氧化剂介孔铈掺杂生物活性玻璃纳米颗粒

介孔生物活性玻璃纳米颗粒(MBGNs)是新兴的生物材料,用于骨修复/再生,考虑到它们有利的促成骨和促血管生成活性。为了进一步改善其治疗效果,MBGNs具有额外的抗氧化特性对于靶向与骨重塑和疾病相关的氧化应激尤为重要。为此,我们通过使用后浸渍策略并入Ce,开发了抗氧化剂含铈的MBGNs(Ce-MBGNs)(粒径为100–300 nm),从而保留了纳米颗粒的形状,孔结构和分散性。可以通过调整Ce前体溶液的浓度来调整Ce的掺入量。当在相对较低的温度(20°C)中浸渍时,Ce-MBGNs含有1.8或2。产生了8 mol%的Ce,同时可以避免形成副产物氧化铈纳米颗粒(nanoceria)。在两个发达的Ce-MBGNs中,Ce的浓度4+高于Ce 3+,而Ce 4+的相对摩尔百分比在两种Ce-MBGNs中相似(〜74%)。证明所获得的Ce-MBGNs在1 mg / mL的浓度下对成纤维细胞无细胞毒性。此外,将Ce掺入MBGNs中可显着降低巨噬细胞中与氧化应激相关的基因的表达(J774a.1)。特别是在存在氧化剂的情况下,与聚苯乙烯板相比,Ce-MBGNs可以下调与氧化应激相关的基因的表达(对照)。当与Ce-MBGNs培养时,与MBGNs和对照相比,巨噬细胞中促炎相关基因的表达也可能被下调。Ce-MBGNs还通过抑制促破骨细胞作用而表现出促成骨活性。获得的结果凸显了已开发的Ce-MBGN在各种生物医学应用中的巨大潜力,

更新日期:2020-01-09
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