Nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathways

IF 8.6 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Npg Asia Materials Pub Date : 2024-03-22 DOI:10.1038/s41427-024-00535-x
Shijia Tang, Yue Yan, Xiaoli Lu, Peng Wang, Xueqin Xu, Ke Hu, Sen Yan, Zhaobin Guo, Xiao Han, Feimin Zhang, Ning Gu
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Abstract

Physical factors in the cellular microenvironment have critical effects on stem cell differentiation. The utilization of physical factors to promote the osteogenic differentiation of stem cells has been established as a new strategy for developing bone tissue engineering scaffolds. In this context, scaffolds with multiscale anisotropy are considered to possess biomimetic properties, which are advantageous for their biological performance. In the present study, a novel magnetic anisotropic hydrogel (MAH) with magnetic and topographic anisotropy was designed by combining static magnetic field-induced magnetic nanomaterials and a hydrogel. In in vitro studies, the MAH exhibited excellent biocompatibility and osteogenic bioactivity. The alkaline phosphatase activity and the expression of osteogenic-related genes and proteins induced by the MAH were greater than those induced by the pure PEGDA–GelMA hydrogel (PGH) and the magnetic isotropic hydrogel (MIH). In addition, the present study revealed that the dual anisotropic properties of the MAH activated the NOTCH1/2 pathway by upregulating SNHG5 and downstream SIRT6, which modulates the level of NOTCH1/2 by antagonizing DNMT1 protein stability, ultimately inducing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, the MAH, MIH, and PGH were tested for in vivo bone regeneration in rabbits with femur defects, and the results demonstrated that the MAH effectively stimulated bone regeneration. Taken together, these findings suggest that this magnetically and topographically anisotropic biomimetic hydrogel might be a promising candidate for application in the field of bone tissue regeneration.

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具有双重各向异性的纳米复合磁性水凝胶通过 NOTCH 依赖性途径诱导骨生成
细胞微环境中的物理因素对干细胞分化有至关重要的影响。利用物理因素促进干细胞成骨分化已被确立为开发骨组织工程支架的新策略。在这种情况下,具有多尺度各向异性的支架被认为具有生物仿生特性,这对其生物学性能十分有利。在本研究中,通过将静态磁场诱导的磁性纳米材料与水凝胶相结合,设计出了一种具有磁性和地形各向异性的新型磁性各向异性水凝胶(MAH)。在体外研究中,MAH 表现出优异的生物相容性和成骨生物活性。与纯 PEGDA-GelMA 水凝胶(PGH)和磁性各向同性水凝胶(MIH)相比,MAH 诱导的碱性磷酸酶活性以及成骨相关基因和蛋白质的表达量更高。此外,本研究还发现,MAH的双重各向异性特性通过上调SNHG5和下游SIRT6激活了NOTCH1/2通路,而SIRT6则通过拮抗DNMT1蛋白的稳定性调节NOTCH1/2的水平,最终诱导骨髓间充质干细胞(BMSCs)的成骨分化。此外,还对 MAH、MIH 和 PGH 在股骨缺损家兔体内的骨再生进行了测试,结果表明 MAH 能有效刺激骨再生。综上所述,这些研究结果表明,这种具有磁性和地形各向异性的仿生水凝胶有望应用于骨组织再生领域。
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来源期刊
Npg Asia Materials
Npg Asia Materials MATERIALS SCIENCE, MULTIDISCIPLINARY-
CiteScore
15.40
自引率
1.00%
发文量
87
审稿时长
2 months
期刊介绍: NPG Asia Materials is an open access, international journal that publishes peer-reviewed review and primary research articles in the field of materials sciences. The journal has a global outlook and reach, with a base in the Asia-Pacific region to reflect the significant and growing output of materials research from this area. The target audience for NPG Asia Materials is scientists and researchers involved in materials research, covering a wide range of disciplines including physical and chemical sciences, biotechnology, and nanotechnology. The journal particularly welcomes high-quality articles from rapidly advancing areas that bridge the gap between materials science and engineering, as well as the classical disciplines of physics, chemistry, and biology. NPG Asia Materials is abstracted/indexed in Journal Citation Reports/Science Edition Web of Knowledge, Google Scholar, Chemical Abstract Services, Scopus, Ulrichsweb (ProQuest), and Scirus.
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