Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small “dynamic bridges” to regulate BMSC behaviors for osteochondral regeneration
The dynamic extracellular matrix (ECM) constantly affects the behaviors of cells. To mimic the dynamics of ECM with controllable stiffness and energy dissipation, this study proposes a strategy in which a small molecule, 3,4-dihydroxybenzaldehyde (DB), was used as fast “dynamic bridges'’ to con...
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KeAi Communications Co., Ltd.
2023-07-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22003243 |
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author | Changjiang Liu Qifan Yu Zhangqin Yuan Qianping Guo Xiting Liao Feng Han Tao Feng Guoping Liu Runze Zhao Zhuang Zhu Haijiao Mao Caihong Zhu Bin Li |
author_facet | Changjiang Liu Qifan Yu Zhangqin Yuan Qianping Guo Xiting Liao Feng Han Tao Feng Guoping Liu Runze Zhao Zhuang Zhu Haijiao Mao Caihong Zhu Bin Li |
author_sort | Changjiang Liu |
collection | DOAJ |
description | The dynamic extracellular matrix (ECM) constantly affects the behaviors of cells. To mimic the dynamics of ECM with controllable stiffness and energy dissipation, this study proposes a strategy in which a small molecule, 3,4-dihydroxybenzaldehyde (DB), was used as fast “dynamic bridges'’ to construct viscoelastic gelatin methacryloyl (GelMA)-based hydrogels. The storage modulus and loss modulus of hydrogels were independently adjusted by the covalent crosslinking density and by the number of dynamic bonds. The hydrogels exhibited self-healing property, injectability, excellent adhesion and mechanical properties. Moreover, the in vitro results revealed that the viscous dissipation of hydrogels favored the spreading, proliferation, osteogenesis and chondrogenesis of bone marrow mesenchymal stem cells (BMSCs), but suppressed their adipogenesis. RNA-sequencing and immunofluorescence suggested that the viscous dissipation of hydrogels activated Yes-associated protein (YAP) by stabilizing integrin β1, and further promoted nuclear translocation of smad2/3 and β-catenin to enhance chondrogenesis and osteogenesis. As a result, the viscoelastic GelMA hydrogels with highest loss modulus showed best effect in cartilage and subchondral bone repair. Taken together, findings from this study reveal an effective strategy to fabricate viscoelastic hydrogels for modulating the interactions between cells and dynamic ECM to promote tissue regeneration. |
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spelling | doaj.art-06893267aea048cfb757a80156bc6b4c2024-04-28T03:33:01ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-07-0125445459Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small “dynamic bridges” to regulate BMSC behaviors for osteochondral regenerationChangjiang Liu0Qifan Yu1Zhangqin Yuan2Qianping Guo3Xiting Liao4Feng Han5Tao Feng6Guoping Liu7Runze Zhao8Zhuang Zhu9Haijiao Mao10Caihong Zhu11Bin Li12College of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaCollege of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, ChinaDepartment of Orthopaedic Surgery, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China; Corresponding author.College of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China; Corresponding author.College of Chemistry, Chemical Engineering and Materials Science, Orthopaedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China; Department of Orthopaedic Surgery, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, China; Corresponding author. Rm 201 Bldg Jiwu, Soochow University (North Campus), 178 Ganjiang Rd, Suzhou, Jiangsu, 215007, China.The dynamic extracellular matrix (ECM) constantly affects the behaviors of cells. To mimic the dynamics of ECM with controllable stiffness and energy dissipation, this study proposes a strategy in which a small molecule, 3,4-dihydroxybenzaldehyde (DB), was used as fast “dynamic bridges'’ to construct viscoelastic gelatin methacryloyl (GelMA)-based hydrogels. The storage modulus and loss modulus of hydrogels were independently adjusted by the covalent crosslinking density and by the number of dynamic bonds. The hydrogels exhibited self-healing property, injectability, excellent adhesion and mechanical properties. Moreover, the in vitro results revealed that the viscous dissipation of hydrogels favored the spreading, proliferation, osteogenesis and chondrogenesis of bone marrow mesenchymal stem cells (BMSCs), but suppressed their adipogenesis. RNA-sequencing and immunofluorescence suggested that the viscous dissipation of hydrogels activated Yes-associated protein (YAP) by stabilizing integrin β1, and further promoted nuclear translocation of smad2/3 and β-catenin to enhance chondrogenesis and osteogenesis. As a result, the viscoelastic GelMA hydrogels with highest loss modulus showed best effect in cartilage and subchondral bone repair. Taken together, findings from this study reveal an effective strategy to fabricate viscoelastic hydrogels for modulating the interactions between cells and dynamic ECM to promote tissue regeneration.http://www.sciencedirect.com/science/article/pii/S2452199X22003243Viscoelastic hydrogelsDynamic bondsGelMADissipationOsteochondral regeneration |
spellingShingle | Changjiang Liu Qifan Yu Zhangqin Yuan Qianping Guo Xiting Liao Feng Han Tao Feng Guoping Liu Runze Zhao Zhuang Zhu Haijiao Mao Caihong Zhu Bin Li Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small “dynamic bridges” to regulate BMSC behaviors for osteochondral regeneration Bioactive Materials Viscoelastic hydrogels Dynamic bonds GelMA Dissipation Osteochondral regeneration |
title | Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small “dynamic bridges” to regulate BMSC behaviors for osteochondral regeneration |
title_full | Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small “dynamic bridges” to regulate BMSC behaviors for osteochondral regeneration |
title_fullStr | Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small “dynamic bridges” to regulate BMSC behaviors for osteochondral regeneration |
title_full_unstemmed | Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small “dynamic bridges” to regulate BMSC behaviors for osteochondral regeneration |
title_short | Engineering the viscoelasticity of gelatin methacryloyl (GelMA) hydrogels via small “dynamic bridges” to regulate BMSC behaviors for osteochondral regeneration |
title_sort | engineering the viscoelasticity of gelatin methacryloyl gelma hydrogels via small dynamic bridges to regulate bmsc behaviors for osteochondral regeneration |
topic | Viscoelastic hydrogels Dynamic bonds GelMA Dissipation Osteochondral regeneration |
url | http://www.sciencedirect.com/science/article/pii/S2452199X22003243 |
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