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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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2025-03-01
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.
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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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