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载 bFGF 的介孔硅纳米颗粒通过 Wnt/β-连环蛋白信号通路促进骨再生。

bFGF-Loaded Mesoporous Silica Nanoparticles Promote Bone Regeneration Through the Wnt/β-Catenin Signalling Pathway.

机构信息

School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China.

出版信息

Int J Nanomedicine. 2022 Jun 7;17:2593-2608. doi: 10.2147/IJN.S366926. eCollection 2022.

Abstract

BACKGROUND

Bone defects remain an unsolved clinical problem due to the lack of effective osteogenic induction protocols. Nanomaterials play an important role in bone defect repair by stimulating osteogenesis. However, constructing an effective bioactive nanomaterial remains a substantial challenge.

METHODS

In this study, mesoporous silica nanoparticles (MSNs) were prepared and used as nanocarriers for basic fibroblast growth factor (bFGF). The characteristics and biological properties of the synthetic bFGF@MSNs were tested. The osteogenic effects of the particles on the behavior of MC3T3-E1 cells were investigated in vitro. In addition, the differentially expressed genes during induction of osteogenesis were analyzed by transcriptomic sequencing. Radiological and histological observations were carried out to determine bone regeneration capability in a distal femur defect model.

RESULTS

Achieving bFGF sustained release, bFGF@MSNs had uniform spherical morphology and good biocompatibility. In vitro osteogenesis induction experiments showed that bFGF@MSNs exhibited excellent osteogenesis performance, with upregulation of osteogenesis-related genes (RUNX2, OCN, Osterix, ALP). Transcriptomic sequencing revealed that the Wnt/β-catenin signalling pathway could be activated in regulation of biological processes. In vivo, bone defect repair experiments showed enhanced bone regeneration, as indicated by radiological and histological analysis, after the application of bFGF@MSNs.

CONCLUSION

bFGF@MSNs can promote bone regeneration by activating the Wnt/β-catenin signalling pathway. These particles are expected to become a potential therapeutic bioactive material for clinical application in repairing bone defects in the future.

摘要

背景

由于缺乏有效的成骨诱导方案,骨缺损仍然是一个未解决的临床问题。纳米材料通过刺激成骨在骨缺损修复中起着重要作用。然而,构建有效的生物活性纳米材料仍然是一个巨大的挑战。

方法

在这项研究中,制备了介孔硅纳米粒子(MSNs)并用作碱性成纤维细胞生长因子(bFGF)的纳米载体。测试了合成的 bFGF@MSNs 的特性和生物学性质。在体外研究了颗粒对 MC3T3-E1 细胞行为的成骨作用。此外,通过转录组测序分析了成骨诱导过程中差异表达的基因。进行放射学和组织学观察以确定在远端股骨缺损模型中的骨再生能力。

结果

实现 bFGF 持续释放,bFGF@MSNs 具有均匀的球形形态和良好的生物相容性。体外成骨诱导实验表明,bFGF@MSNs 表现出优异的成骨性能,上调成骨相关基因(RUNX2、OCN、Osterix、ALP)。转录组测序显示 Wnt/β-catenin 信号通路可以被激活以调节生物学过程。在体内,骨缺损修复实验表明,应用 bFGF@MSNs 后,放射学和组织学分析表明骨再生增强。

结论

bFGF@MSNs 通过激活 Wnt/β-catenin 信号通路促进骨再生。这些颗粒有望成为未来临床应用于修复骨缺损的潜在治疗性生物活性材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dc4/9188412/80fd665b794a/IJN-17-2593-g0001.jpg

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