Although much research has gone into the design of nanomaterials, inflammatory response still impedes the capacity of nanomaterial-induced tissue regeneration. In-situ incorporation of nutrient elements in silica-based biomaterials has emerged as a new option to endow the nanomaterials modulating biological reactions. In this work, europium-doped mesoporous silica nanospheres (Eu-MSNs) were successfully synthesized via a one-pot method. The nanospheres (size of 280–300 nm) possess uniformly spherical morphology and mesoporous structure, and well distributed Eu elements. The nanospheres show distinct fluorescent property at 615 nm for potential bio-labeling. Noticeably, the Eu-MSNs stimulate pro-inflammatory response of macrophages and induce a modulated immune microenvironment, which further activates the osteogenic differentiation of bone marrow stromal cells (BMSCs) as well as angiogenic activity of human umbilical vein endothelial cells (HUVECs). During the process, osteogenesis-related genes (e.g. ALP, OCN, OPN and COL-I) of BMSCs, and angiogenesis-related genes (e.g. CD31, MMP9, VEGFR1/2, and PDGFRα/β) of HUVECs were significantly upregulated by Eu-MSNs modulating immune environment of macrophages. The in vivo study further demonstrated that the Eu-MSNs could not only stimulate osteogenesis by accelerating the new bone formation at critical-sized cranial defect site, but also support the blood vessel formation as well as collagen deposition and re-epithelialization at chronic skin wound sites, showing an improved angiogenesis activity when comparing with MSNs alone. Given the easy handling characteristics and extensive application potential, the results suggest that Eu-MSNs could be used as immunity-modulated osteogenesis/angiogenesis agent for skin and bone regeneration.

尽管对纳米材料的设计进行了大量研究，但是炎症反应仍然阻碍了纳米材料诱导的组织再生的能力。原位在二氧化硅基生物材料中掺入营养元素已成为赋予纳米材料调节生物反应的新选择。在这项工作中，通过一锅法成功地合成了掺do介孔二氧化硅纳米球（Eu-MSNs）。纳米球（尺寸为280-300 nm）具有均匀的球形形态和中孔结构，以及分布均匀的Eu元素。纳米球在615 nm处显示出独特的荧光特性，可用于潜在的生物标记。值得注意的是，Eu-MSN刺激巨噬细胞的促炎反应并诱导调节的免疫微环境，从而进一步激活骨髓基质细胞（BMSC）的成骨分化以及人脐静脉内皮细胞（HUVEC）的血管生成活性。在此过程中，与成骨相关的基因（例如ALP，OCN，OPN和COL-I）的骨髓基质细胞，和血管发生相关的基因（例如CD31，MMP9，VEGFR1 / 2，和HUVEC的PDGFRα/β）通过铕的MSN调节巨噬细胞的免疫环境中显著上调。在体内研究进一步证明，Eu-MSNs不仅可以通过加速关键尺寸颅骨缺损部位的新骨形成来刺激成骨，而且还可以支持血管形成以及慢性皮肤伤口部位的胶原蛋白沉积和上皮再形成，表明与单独使用MSN相比，可改善血管生成活性。鉴于其易于处理的特性和广泛的应用潜力，结果表明Eu-MSNs可用作免疫调节的成骨/血管生成剂，用于皮肤和骨骼的再生。