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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Main Authors: 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
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2023-07-01
Series:Bioactive Materials
Subjects:
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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