Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone Regeneration
Abstract Stem cell implantation holds promise for enhancing bone repair, but risks of pathogen transmission and malignant cell transformation should not be ignored. Compared to stem cell implantation, recruitment of endogenous stem cells to injured sites is more critical for in situ bone regeneratio...
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| Format: | Article |
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202415772 |
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| author | Yao Xiao Jinjin Ma Xiaonan Yuan Huan Wang Fengyu Ma Jun Wu Qianglong Chen Jie Hu Lijie Wang Zhendong Zhang Chao Wang Jiaying Li Weishan Wang Bin Li |
| author_facet | Yao Xiao Jinjin Ma Xiaonan Yuan Huan Wang Fengyu Ma Jun Wu Qianglong Chen Jie Hu Lijie Wang Zhendong Zhang Chao Wang Jiaying Li Weishan Wang Bin Li |
| author_sort | Yao Xiao |
| collection | DOAJ |
| description | Abstract Stem cell implantation holds promise for enhancing bone repair, but risks of pathogen transmission and malignant cell transformation should not be ignored. Compared to stem cell implantation, recruitment of endogenous stem cells to injured sites is more critical for in situ bone regeneration. In this study, based on the acidic microenvironment of bone injury, an HG‐AA1:1‐SDF‐1α composite hydrogel with a dual‐control intelligent switch function is developed by incorporating stromal cell‐derived factor (SDF‐1α), arginine carbon dots (Arg‐CDs), and calcium ions (Ca2+) into the oxidized hyaluronic acid/gelatin methacryloyl (HG) hydrogel. The acidic microenvironment triggers the first switch (Schiff base bond is broken between HG‐AA1:1 and SDF‐1α) of HG‐AA1:1‐SDF‐1α composite hydrogel to continuously release SDF‐1α. Compared to the neutral (pH 7.4) media, the cumulative release of SDF‐1α in acidic (pH 5.5) media is ≈2.5 times higher, which enhances the migration and recruitment of endogenous mesenchymal stem cells (MSCs). The recruited MSCs immediately initiate the second switch and metabolize Arg‐CDs into the bioactive nitric oxide (NO) in the presence of Ca2+, activating NO/cyclic guanosine monophosphate (cGMP) signaling pathway to promote angiogenesis. Therefore, the engineered HG‐AA1:1‐SDF‐1α composite hydrogel shows promising potential to achieve “coupling osteogenesis and angiogenesis” for bone regeneration. |
| format | Article |
| id | doaj-art-a39d80fd0fdd4a68bf2077fca9d1a427 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-a39d80fd0fdd4a68bf2077fca9d1a4272025-08-20T02:24:47ZengWileyAdvanced Science2198-38442025-03-011211n/an/a10.1002/advs.202415772Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone RegenerationYao Xiao0Jinjin Ma1Xiaonan Yuan2Huan Wang3Fengyu Ma4Jun Wu5Qianglong Chen6Jie Hu7Lijie Wang8Zhendong Zhang9Chao Wang10Jiaying Li11Weishan Wang12Bin Li13The First Affiliated Hospital of Shihezi University Shihezi Xinjiang 832000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaSanitation & Environment Technology Institute of Soochow University Suzhou Jiangsu 215163 ChinaThe First Affiliated Hospital of Shihezi University Shihezi Xinjiang 832000 ChinaThe First Affiliated Hospital of Shihezi University Shihezi Xinjiang 832000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaThe First Affiliated Hospital of Shihezi University Shihezi Xinjiang 832000 ChinaMedical 3D Printing Center Orthopedic Institute Department of Orthopedic Surgery The First Affiliated Hospital School of Basic Medical Sciences MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College Soochow University Suzhou Jiangsu 215000 ChinaAbstract Stem cell implantation holds promise for enhancing bone repair, but risks of pathogen transmission and malignant cell transformation should not be ignored. Compared to stem cell implantation, recruitment of endogenous stem cells to injured sites is more critical for in situ bone regeneration. In this study, based on the acidic microenvironment of bone injury, an HG‐AA1:1‐SDF‐1α composite hydrogel with a dual‐control intelligent switch function is developed by incorporating stromal cell‐derived factor (SDF‐1α), arginine carbon dots (Arg‐CDs), and calcium ions (Ca2+) into the oxidized hyaluronic acid/gelatin methacryloyl (HG) hydrogel. The acidic microenvironment triggers the first switch (Schiff base bond is broken between HG‐AA1:1 and SDF‐1α) of HG‐AA1:1‐SDF‐1α composite hydrogel to continuously release SDF‐1α. Compared to the neutral (pH 7.4) media, the cumulative release of SDF‐1α in acidic (pH 5.5) media is ≈2.5 times higher, which enhances the migration and recruitment of endogenous mesenchymal stem cells (MSCs). The recruited MSCs immediately initiate the second switch and metabolize Arg‐CDs into the bioactive nitric oxide (NO) in the presence of Ca2+, activating NO/cyclic guanosine monophosphate (cGMP) signaling pathway to promote angiogenesis. Therefore, the engineered HG‐AA1:1‐SDF‐1α composite hydrogel shows promising potential to achieve “coupling osteogenesis and angiogenesis” for bone regeneration.https://doi.org/10.1002/advs.202415772acidic microenvironmentArg‐CDs metabolismendogenous stem cells recruitmentosteogenesis and angiogenesis coupling |
| spellingShingle | Yao Xiao Jinjin Ma Xiaonan Yuan Huan Wang Fengyu Ma Jun Wu Qianglong Chen Jie Hu Lijie Wang Zhendong Zhang Chao Wang Jiaying Li Weishan Wang Bin Li Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone Regeneration Advanced Science acidic microenvironment Arg‐CDs metabolism endogenous stem cells recruitment osteogenesis and angiogenesis coupling |
| title | Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone Regeneration |
| title_full | Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone Regeneration |
| title_fullStr | Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone Regeneration |
| title_full_unstemmed | Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone Regeneration |
| title_short | Acid‐Triggered Dual‐Functional Hydrogel Platform for Enhanced Bone Regeneration |
| title_sort | acid triggered dual functional hydrogel platform for enhanced bone regeneration |
| topic | acidic microenvironment Arg‐CDs metabolism endogenous stem cells recruitment osteogenesis and angiogenesis coupling |
| url | https://doi.org/10.1002/advs.202415772 |
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