Nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathways
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...
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Nature Portfolio
2024-03-01
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| Series: | NPG Asia Materials |
| Online Access: | https://doi.org/10.1038/s41427-024-00535-x |
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| author | Shijia Tang Yue Yan Xiaoli Lu Peng Wang Xueqin Xu Ke Hu Sen Yan Zhaobin Guo Xiao Han Feimin Zhang Ning Gu |
| author_facet | Shijia Tang Yue Yan Xiaoli Lu Peng Wang Xueqin Xu Ke Hu Sen Yan Zhaobin Guo Xiao Han Feimin Zhang Ning Gu |
| author_sort | Shijia Tang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ca6375397814e5db8afcbc2a7b704cf |
| institution | Kabale University |
| issn | 1884-4057 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
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| series | NPG Asia Materials |
| spelling | doaj-art-5ca6375397814e5db8afcbc2a7b704cf2025-01-19T12:28:23ZengNature PortfolioNPG Asia Materials1884-40572024-03-0116111510.1038/s41427-024-00535-xNanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathwaysShijia Tang0Yue Yan1Xiaoli Lu2Peng Wang3Xueqin Xu4Ke Hu5Sen Yan6Zhaobin Guo7Xiao Han8Feimin Zhang9Ning Gu10Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical UniversityDivision of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing UniversityKey Laboratory for Bio-Electromagnetic Environment and Advanced Medical Theranostics, School of Biomedical Engineering and Informatics, Nanjing Medical UniversityCardiovascular Disease Research Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Medical School, Nanjing UniversityShanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese MedicineJiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical UniversityJiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical UniversityKey Laboratory for Bio-Electromagnetic Environment and Advanced Medical Theranostics, School of Biomedical Engineering and Informatics, Nanjing Medical UniversityAbstract 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.https://doi.org/10.1038/s41427-024-00535-x |
| spellingShingle | Shijia Tang Yue Yan Xiaoli Lu Peng Wang Xueqin Xu Ke Hu Sen Yan Zhaobin Guo Xiao Han Feimin Zhang Ning Gu Nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathways NPG Asia Materials |
| title | Nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathways |
| title_full | Nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathways |
| title_fullStr | Nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathways |
| title_full_unstemmed | Nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathways |
| title_short | Nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the NOTCH-dependent pathways |
| title_sort | nanocomposite magnetic hydrogel with dual anisotropic properties induces osteogenesis through the notch dependent pathways |
| url | https://doi.org/10.1038/s41427-024-00535-x |
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