Titania nanotubes (TNT) generated on titanium implant are emerged as important modification technique to facilitate bone regeneration. Mesenchymal stem cells (MSCs)-derived exosomes are membrane bound extracellular vesicles (EVs), which play an important role in tissue regeneration. The objective of this study was to generate an EVs hybrid TNT aiming at regulating inflammation, MSCs recruitment and osteogenesis. We isolated EVs from MSCs (MSCs EVs) and 3-day osteogenically differentiated MSCs (3d EVs). MSC EVs and 3d EVs exhibited round morphology under TEM, which also showed robust internalization by human bone marrow derived MSCs (hBMSCs). Next, we fabricated 3d EVs/MSC EVs hybrid TNT. When inflammatory macrophages were co-cultured with EVs hybrid TNT, the gene and protein expression of inflammatory cytokine were significantly reduced. Macrophage morphology was also examined by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Further migratory ability study using hBMSCs indicated significant enhancement of MSCs migration in EVs hybrid TNT. In addition, we further demonstrated significant increase of osteogenic differentiation of hBMSCs in EVs hybrid TNT. This study suggests that EVs hybrid TNT may serve as a viable therapeutic approach to enhance osteogenesis and bone regeneration.

中文翻译：

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二氧化钛纳米管与双层细胞外囊泡的表面工程调节炎症和成骨

在钛植入物上生成的二氧化钛纳米管（TNT）已成为促进骨再生的重要修饰技术。间充质干细胞（MSC）衍生的外泌体是膜结合的细胞外囊泡（EV），在组织再生中发挥重要作用。本研究的目的是生成一种 EV 混合 TNT，旨在调节炎症、MSC 募集和成骨。我们从 MSC (MSC EV) 和 3 天成骨分化 MSC (3d EV) 中分离出 EV。MSC EV 和 3d EV 在 TEM 下表现出圆形形态，这也显示出人骨髓来源的 MSC (hBMSC) 的强大内化作用。接下来，我们制造了 3d EV/MSC EV 混合 TNT。当炎症巨噬细胞与EVs杂交TNT共培养时，炎症细胞因子的基因和蛋白表达显着降低。还通过共焦激光扫描显微镜（CLSM）和扫描电子显微镜（SEM）检查巨噬细胞形态。使用 hBMSC 进行的进一步迁移能力研究表明，EV 混合 TNT 中 MSC 的迁移显着增强。此外，我们进一步证明了 EVs 混合 TNT 中 hBMSC 的成骨分化显着增加。这项研究表明，EVs 混合 TNT 可能作为增强成骨和骨再生的可行治疗方法。