Injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarization
Substrate stiffness can regulate macrophage polarization to support tissue repair in tissue engineering applications. Understanding the mechanisms of stiffness sensing is valuable for applying this knowledge to stiffness-related inflammatory diseases. In this study, we examined IACs-related integrin...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Polymer Testing |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0142941824003623 |
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| _version_ | 1841555749925289984 |
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| author | Jinxin Wu Bing Han Shili Ai Aijing Wang Yilin Song Moran Jin Xiaozhong Qu Xiaoyan Wang |
| author_facet | Jinxin Wu Bing Han Shili Ai Aijing Wang Yilin Song Moran Jin Xiaozhong Qu Xiaoyan Wang |
| author_sort | Jinxin Wu |
| collection | DOAJ |
| description | Substrate stiffness can regulate macrophage polarization to support tissue repair in tissue engineering applications. Understanding the mechanisms of stiffness sensing is valuable for applying this knowledge to stiffness-related inflammatory diseases. In this study, we examined IACs-related integrins related to stiffness-sensitive macrophage polarization by constructing an injectable double-network (DN) hydrogel with varying stiffness. Inflammatory cytokine expression decreased as substrate stiffness increased (from 19.9 to 125.7 kPa), with medium stiffness (84.8 kPa) inducing macrophages to an increased level of anti-inflammatory polarization. Improved adhesion and elevated expression levels of ITGA5, ITGA3, and ITGAV in macrophages on the softer hydrogels highlighted the role of integrins in stiffness-regulated macrophage polarization. Inhibition of integrins using ethylenediaminetetraacetic acid (EDTA) abolished differences in macrophage polarization across the three groups, further confirming the central role of integrins. These findings suggest that, in tissue engineering, selecting appropriate substrate stiffness or gradient stiffness hydrogel could align with the optimal mechanical environment required for specific cell growth and function. Additionally, the critical role of integrins in mediating mechanical transduction may provide new therapeutic targets for treating certain stiffness-related inflammatory diseases. |
| format | Article |
| id | doaj-art-6ba17d6fd36b40bc9e6724b1178b5d9f |
| institution | Kabale University |
| issn | 1873-2348 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Polymer Testing |
| spelling | doaj-art-6ba17d6fd36b40bc9e6724b1178b5d9f2025-01-08T04:52:11ZengElsevierPolymer Testing1873-23482025-02-01143108685Injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarizationJinxin Wu0Bing Han1Shili Ai2Aijing Wang3Yilin Song4Moran Jin5Xiaozhong Qu6Xiaoyan Wang7Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, ChinaDepartment of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, ChinaCollege of Materials Science and Opto-electronic Technology, University of Chinese Academy of Sciences, Beijing, ChinaDepartment of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, ChinaDepartment of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, ChinaDepartment of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, ChinaCollege of Materials Science and Opto-electronic Technology, University of Chinese Academy of Sciences, Beijing, China; Corresponding author.Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China; Corresponding author.Substrate stiffness can regulate macrophage polarization to support tissue repair in tissue engineering applications. Understanding the mechanisms of stiffness sensing is valuable for applying this knowledge to stiffness-related inflammatory diseases. In this study, we examined IACs-related integrins related to stiffness-sensitive macrophage polarization by constructing an injectable double-network (DN) hydrogel with varying stiffness. Inflammatory cytokine expression decreased as substrate stiffness increased (from 19.9 to 125.7 kPa), with medium stiffness (84.8 kPa) inducing macrophages to an increased level of anti-inflammatory polarization. Improved adhesion and elevated expression levels of ITGA5, ITGA3, and ITGAV in macrophages on the softer hydrogels highlighted the role of integrins in stiffness-regulated macrophage polarization. Inhibition of integrins using ethylenediaminetetraacetic acid (EDTA) abolished differences in macrophage polarization across the three groups, further confirming the central role of integrins. These findings suggest that, in tissue engineering, selecting appropriate substrate stiffness or gradient stiffness hydrogel could align with the optimal mechanical environment required for specific cell growth and function. Additionally, the critical role of integrins in mediating mechanical transduction may provide new therapeutic targets for treating certain stiffness-related inflammatory diseases.http://www.sciencedirect.com/science/article/pii/S0142941824003623HydrogelStiffnessMacrophagesPolarizationIntegrin |
| spellingShingle | Jinxin Wu Bing Han Shili Ai Aijing Wang Yilin Song Moran Jin Xiaozhong Qu Xiaoyan Wang Injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarization Polymer Testing Hydrogel Stiffness Macrophages Polarization Integrin |
| title | Injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarization |
| title_full | Injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarization |
| title_fullStr | Injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarization |
| title_full_unstemmed | Injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarization |
| title_short | Injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarization |
| title_sort | injectable double network hydrogel with adjustable stiffness for modulation of macrophage polarization |
| topic | Hydrogel Stiffness Macrophages Polarization Integrin |
| url | http://www.sciencedirect.com/science/article/pii/S0142941824003623 |
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