Self-assembled antioxidant enzyme-mimicking hydrogel: Targeting oxidative stress and macrophage organization for improving degenerated intervertebral discs
Intervertebral disc degeneration (IVDD) is a major contributor to lower back pain. At present, antioxidant therapy is regarded as one of the most promising strategies for treating IVDD, due to the critical role of reactive oxygen species (ROS) in its pathogenesis. Herein, we presented a self-assembl...
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Elsevier
2025-04-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425001449 |
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| author | Yudong Fu Hua Sun Yongchao Jin Shaohui Cheng Yanyi Wu Chen Liu Lei Fan Juqun Xi Shixin Li Liang Zhang |
| author_facet | Yudong Fu Hua Sun Yongchao Jin Shaohui Cheng Yanyi Wu Chen Liu Lei Fan Juqun Xi Shixin Li Liang Zhang |
| author_sort | Yudong Fu |
| collection | DOAJ |
| description | Intervertebral disc degeneration (IVDD) is a major contributor to lower back pain. At present, antioxidant therapy is regarded as one of the most promising strategies for treating IVDD, due to the critical role of reactive oxygen species (ROS) in its pathogenesis. Herein, we presented a self-assembled hydrogel, termed MnGAHs, formed through the crossing of manganese ions (Mn2+) and glycyrrheic acid (GA), which possessed the activities of antioxidant enzymes, including catalase (CAT) and superoxide dismutase (SOD). The obtained MnGAHs effectively scavenge ROS, reducing oxidative stress levels and alleviating the senescence of nucleus pulposus-derived mesenchymal stem cells (NPMSC), thereby mitigating IVDD. Furthermore, MnGAHs also promoted macrophage polarization towards M2 phenotype, reducing the inflammatory response and thereby inhibiting the progression of IVDD. By combining theoretical calculations with analyses of public databases, we revealed that the ROS-p53-p21 axis played a crucial role in the function of MnGAHs to reverse IVDD, a finding further confirmed by Western blot analysis. As a result, the injection of MnGAHs into the intervertebral disc (IVD) significantly alleviated the degeneration process in a rat model of puncture-induced IVDD. Therefore, the as-prepared antioxidant enzyme-mimicking hydrogels provide a promising and effective approach for treating IVDD. |
| format | Article |
| id | doaj-art-35fa8e429e804a97a2cd2aadf5a91858 |
| institution | DOAJ |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-35fa8e429e804a97a2cd2aadf5a918582025-08-20T03:15:48ZengElsevierMaterials Today Bio2590-00642025-04-013110158610.1016/j.mtbio.2025.101586Self-assembled antioxidant enzyme-mimicking hydrogel: Targeting oxidative stress and macrophage organization for improving degenerated intervertebral discsYudong Fu0Hua Sun1Yongchao Jin2Shaohui Cheng3Yanyi Wu4Chen Liu5Lei Fan6Juqun Xi7Shixin Li8Liang Zhang9Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, 225001, PR ChinaInstitute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, 225001, PR China; Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225001, PR ChinaCollege of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu, 225009, PR ChinaSchool of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, 225002, PR ChinaInstitute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, 225001, PR ChinaInstitute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, 225001, PR China; Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225001, PR ChinaSchool of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, 225002, PR ChinaInstitute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, 225001, PR China; The Key Laboratory of the Jiangsu Higher Education Institutions for Integrated Traditional Chinese and Western Medicine in Senile Diseases Control (Yangzhou University), Yangzhou, Jiangsu, 225001, PR China; Corresponding author. Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu, 225001, PR China.College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu, 225009, PR China; Corresponding author.Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225001, PR China; Corresponding author.Intervertebral disc degeneration (IVDD) is a major contributor to lower back pain. At present, antioxidant therapy is regarded as one of the most promising strategies for treating IVDD, due to the critical role of reactive oxygen species (ROS) in its pathogenesis. Herein, we presented a self-assembled hydrogel, termed MnGAHs, formed through the crossing of manganese ions (Mn2+) and glycyrrheic acid (GA), which possessed the activities of antioxidant enzymes, including catalase (CAT) and superoxide dismutase (SOD). The obtained MnGAHs effectively scavenge ROS, reducing oxidative stress levels and alleviating the senescence of nucleus pulposus-derived mesenchymal stem cells (NPMSC), thereby mitigating IVDD. Furthermore, MnGAHs also promoted macrophage polarization towards M2 phenotype, reducing the inflammatory response and thereby inhibiting the progression of IVDD. By combining theoretical calculations with analyses of public databases, we revealed that the ROS-p53-p21 axis played a crucial role in the function of MnGAHs to reverse IVDD, a finding further confirmed by Western blot analysis. As a result, the injection of MnGAHs into the intervertebral disc (IVD) significantly alleviated the degeneration process in a rat model of puncture-induced IVDD. Therefore, the as-prepared antioxidant enzyme-mimicking hydrogels provide a promising and effective approach for treating IVDD.http://www.sciencedirect.com/science/article/pii/S2590006425001449HydrogelsEnzyme-mimicking activitiesIntervertebral disc degenerationInflammationMacrophage polarization |
| spellingShingle | Yudong Fu Hua Sun Yongchao Jin Shaohui Cheng Yanyi Wu Chen Liu Lei Fan Juqun Xi Shixin Li Liang Zhang Self-assembled antioxidant enzyme-mimicking hydrogel: Targeting oxidative stress and macrophage organization for improving degenerated intervertebral discs Materials Today Bio Hydrogels Enzyme-mimicking activities Intervertebral disc degeneration Inflammation Macrophage polarization |
| title | Self-assembled antioxidant enzyme-mimicking hydrogel: Targeting oxidative stress and macrophage organization for improving degenerated intervertebral discs |
| title_full | Self-assembled antioxidant enzyme-mimicking hydrogel: Targeting oxidative stress and macrophage organization for improving degenerated intervertebral discs |
| title_fullStr | Self-assembled antioxidant enzyme-mimicking hydrogel: Targeting oxidative stress and macrophage organization for improving degenerated intervertebral discs |
| title_full_unstemmed | Self-assembled antioxidant enzyme-mimicking hydrogel: Targeting oxidative stress and macrophage organization for improving degenerated intervertebral discs |
| title_short | Self-assembled antioxidant enzyme-mimicking hydrogel: Targeting oxidative stress and macrophage organization for improving degenerated intervertebral discs |
| title_sort | self assembled antioxidant enzyme mimicking hydrogel targeting oxidative stress and macrophage organization for improving degenerated intervertebral discs |
| topic | Hydrogels Enzyme-mimicking activities Intervertebral disc degeneration Inflammation Macrophage polarization |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425001449 |
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