Local H2 release remodels senescence microenvironment for improved repair of injured bone

Abstract The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H2 supply can remodel the senescence microenvironment by anti-inflammati...

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Main Authors: Shengqiang Chen, Yuanman Yu, Songqing Xie, Danna Liang, Wei Shi, Sizhen Chen, Guanglin Li, Wei Tang, Changsheng Liu, Qianjun He
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-43618-z
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author Shengqiang Chen
Yuanman Yu
Songqing Xie
Danna Liang
Wei Shi
Sizhen Chen
Guanglin Li
Wei Tang
Changsheng Liu
Qianjun He
author_facet Shengqiang Chen
Yuanman Yu
Songqing Xie
Danna Liang
Wei Shi
Sizhen Chen
Guanglin Li
Wei Tang
Changsheng Liu
Qianjun He
author_sort Shengqiang Chen
collection DOAJ
description Abstract The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H2 supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H2-releasing scaffold which can release high-dosage H2 (911 mL/g, up to 1 week) by electrospraying polyhydroxyalkanoate-encapsulated CaSi2 nanoparticles onto mesoporous bioactive glass. We demonstrate efficient remodeling of the microenvironment and enhanced repair of critical-size bone defects in an aged mouse model. Mechanistically, we reveal that local H2 release alters the microenvironment from pro-inflammation to anti-inflammation by senescent macrophages repolarization and secretome change. We also show that H2 alleviates the progression of aging/injury-superposed senescence, facilitates the recruitment of endogenous cells and the preservation of their regeneration capability, thereby creating a pro-regenerative microenvironment able to support bone defect regeneration.
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spelling doaj.art-b5a895c3463d4bc48c84c69e72f798ed2023-12-03T12:27:22ZengNature PortfolioNature Communications2041-17232023-11-0114111610.1038/s41467-023-43618-zLocal H2 release remodels senescence microenvironment for improved repair of injured boneShengqiang Chen0Yuanman Yu1Songqing Xie2Danna Liang3Wei Shi4Sizhen Chen5Guanglin Li6Wei Tang7Changsheng Liu8Qianjun He9Key Laboratory of Human-Machine-Intelligence Synergic System, Research Center for Neural Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesThe State Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyKey Laboratory of Human-Machine-Intelligence Synergic System, Research Center for Neural Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesGuangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen UniversityKey Laboratory of Human-Machine-Intelligence Synergic System, Research Center for Neural Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesKey Laboratory of Human-Machine-Intelligence Synergic System, Research Center for Neural Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesKey Laboratory of Human-Machine-Intelligence Synergic System, Research Center for Neural Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesKey Laboratory of Human-Machine-Intelligence Synergic System, Research Center for Neural Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesThe State Key Laboratory of Bioreactor Engineering, East China University of Science and TechnologyShanghai Key Laboratory of Hydrogen Science & Center of Hydrogen Science, School of Materials Science and Engineering, Shanghai Jiao Tong UniversityAbstract The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H2 supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H2-releasing scaffold which can release high-dosage H2 (911 mL/g, up to 1 week) by electrospraying polyhydroxyalkanoate-encapsulated CaSi2 nanoparticles onto mesoporous bioactive glass. We demonstrate efficient remodeling of the microenvironment and enhanced repair of critical-size bone defects in an aged mouse model. Mechanistically, we reveal that local H2 release alters the microenvironment from pro-inflammation to anti-inflammation by senescent macrophages repolarization and secretome change. We also show that H2 alleviates the progression of aging/injury-superposed senescence, facilitates the recruitment of endogenous cells and the preservation of their regeneration capability, thereby creating a pro-regenerative microenvironment able to support bone defect regeneration.https://doi.org/10.1038/s41467-023-43618-z
spellingShingle Shengqiang Chen
Yuanman Yu
Songqing Xie
Danna Liang
Wei Shi
Sizhen Chen
Guanglin Li
Wei Tang
Changsheng Liu
Qianjun He
Local H2 release remodels senescence microenvironment for improved repair of injured bone
Nature Communications
title Local H2 release remodels senescence microenvironment for improved repair of injured bone
title_full Local H2 release remodels senescence microenvironment for improved repair of injured bone
title_fullStr Local H2 release remodels senescence microenvironment for improved repair of injured bone
title_full_unstemmed Local H2 release remodels senescence microenvironment for improved repair of injured bone
title_short Local H2 release remodels senescence microenvironment for improved repair of injured bone
title_sort local h2 release remodels senescence microenvironment for improved repair of injured bone
url https://doi.org/10.1038/s41467-023-43618-z
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