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用超低剂量负载银纳米颗粒的二氧化钛纳米管调节破骨细胞活性和免疫反应以促进骨质疏松性骨再生

Modulating Osteoclast Activity and Immune Responses with Ultra-Low-Dose Silver Nanoparticle-Loaded TiO Nanotubes for Osteoporotic Bone Regeneration.

作者信息

Wang Zhen, Xiang Penghui, Xu Zhe, Gu Meiqi, Zhang Rui, Li Yifei, Xin Fei, Yi Chengla

机构信息

Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

J Funct Biomater. 2025 May 4;16(5):162. doi: 10.3390/jfb16050162.

Abstract

INTRODUCTION

Osteoporosis results from the dysregulation of osteoclast activation mechanisms. The subsequent inflammation in osteoporotic environments further hampers bone healing and impedes osseointegration. Therefore, developing treatments that can modulate osteoclast activity and regulate immune responses is essential for effectively treating osteoporotic bone defects.

METHODS

In this study, silver nanoparticle-decorated TiO nanotubes (Ag@TiO-NTs) were synthesized through an electrochemical anodization technique for surface modification. The morphology and elemental composition of the Ag@TiO-NTs structures were characterized using scanning electron microscopy (SEM) and related methods. Subsequently, a series of in vitro and in vivo experiments were conducted to investigate the regenerative potential of Ag@TiO-NTs in osteoporotic bone defects. In vitro assays focused on evaluating cell viability and osteoclast function, while in vivo assessments employed osteoporotic rat models to monitor bone healing via histological examination and micro-computed tomography (micro-CT) imaging.

RESULTS

Our results demonstrated that Ag@TiO, through the controlled release of trace amounts of silver ions, significantly suppressed osteoclast activity and consequently alleviated bone resorption under osteoporotic conditions. In addition, Ag@TiO-NTs facilitated the polarization of macrophages toward the M2 phenotype. These biological effects were associated with the stimulation of autophagy, a fundamental mechanism involved in cellular repair. Moreover, the activation of autophagy contributed to the suppression of RANKL-induced NF-κB signaling, a pathway essential for the regulation of bone metabolism Conclusion: These results suggest that this surface modification strategy has the potential to be an ideal implant biomaterial for treating osteoporotic bone defects and a promising strategy for future implant surgeries.

摘要

引言

骨质疏松症是由破骨细胞激活机制失调引起的。骨质疏松环境中随后发生的炎症会进一步阻碍骨愈合并妨碍骨整合。因此,开发能够调节破骨细胞活性和调节免疫反应的治疗方法对于有效治疗骨质疏松性骨缺损至关重要。

方法

在本研究中,通过电化学阳极氧化技术合成了银纳米颗粒修饰的二氧化钛纳米管(Ag@TiO-NTs)用于表面改性。使用扫描电子显微镜(SEM)和相关方法对Ag@TiO-NTs结构的形态和元素组成进行了表征。随后,进行了一系列体外和体内实验,以研究Ag@TiO-NTs在骨质疏松性骨缺损中的再生潜力。体外试验重点评估细胞活力和破骨细胞功能,而体内评估则采用骨质疏松大鼠模型,通过组织学检查和微计算机断层扫描(micro-CT)成像来监测骨愈合情况。

结果

我们的结果表明,Ag@TiO通过控制释放微量银离子,显著抑制了破骨细胞活性,从而减轻了骨质疏松条件下的骨吸收。此外,Ag@TiO-NTs促进巨噬细胞向M2表型极化。这些生物学效应与自噬的刺激有关,自噬是细胞修复的一种基本机制。此外,自噬的激活有助于抑制RANKL诱导的NF-κB信号通路,这是调节骨代谢的关键途径。结论:这些结果表明,这种表面改性策略有可能成为治疗骨质疏松性骨缺损的理想植入生物材料,也是未来植入手术的一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/692f/12112536/1d12c4162772/jfb-16-00162-g0A1.jpg

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