Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways

<b>Background</b>: Wound healing is a complex and intricate biological process that involves multiple systems within the body and initiates a series of highly coordinated responses to repair damage and restore integrity and functionality. We previously identified that breathing hydrogen...

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Main Authors: Pengxiang Zhao, Yufei Li, Boyuan Guo, Ziyi Liu, Xujuan Zhang, Mengyu Liu, Xuemei Ma
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/3/279
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author Pengxiang Zhao
Yufei Li
Boyuan Guo
Ziyi Liu
Xujuan Zhang
Mengyu Liu
Xuemei Ma
author_facet Pengxiang Zhao
Yufei Li
Boyuan Guo
Ziyi Liu
Xujuan Zhang
Mengyu Liu
Xuemei Ma
author_sort Pengxiang Zhao
collection DOAJ
description <b>Background</b>: Wound healing is a complex and intricate biological process that involves multiple systems within the body and initiates a series of highly coordinated responses to repair damage and restore integrity and functionality. We previously identified that breathing hydrogen can significantly inhibit early inflammation, activate autologous stem cells, and promote the accumulation of extracellular matrix (ECM). However, the broader functions and downstream targets of hydrogen-induced ECM accumulation and tissue remodeling are unknown in the wound-healing process. <b>Methods</b>: Consequently, this thesis developed a hydrogen sustained-release dressing based on a micro storage material and reveals the mechanism of hydrogen in treating wound healing. Upon encapsulating the hydrogen storage materials, magnesium (Mg), and ammonia borane (AB), we found that SiO<sub>2</sub>@Mg exhibits superior sustained-release performance, while SiO<sub>2</sub>@AB demonstrates a higher hydrogen storage capacity. We used a <i>C57/BL6</i> mouse full-thickness skin defect wound model to analyze and compare different hydrogen dressings. <b>Results</b>: It was identified that hydrogen dressings can significantly improve the healing rate of wounds by promoting epithelialization, angiogenesis, and collagen accumulation in wound tissue, and that the effect of slow-release dressings is better than of non-slow-release dressings. We also found that hydrogen dressing can promote transcriptome-level expression related to cell proliferation and differentiation and ECM accumulation, mainly through the <i>Wnt1/β-catenin</i> pathway and <i>TGF-β1/Smad2</i> pathway. <b>Conclusions</b>: Overall, these results provide a novel insight into the field of hydrogen treatment and wound healing.
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spelling doaj-art-97a6690d528646dda097e6c4dbed5f0a2025-08-20T03:43:29ZengMDPI AGPharmaceutics1999-49232025-02-0117327910.3390/pharmaceutics17030279Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad PathwaysPengxiang Zhao0Yufei Li1Boyuan Guo2Ziyi Liu3Xujuan Zhang4Mengyu Liu5Xuemei Ma6College of Chemistry and Life Sciences, Beijing University of Technology, Beijing 100124, ChinaCollege of Chemistry and Life Sciences, Beijing University of Technology, Beijing 100124, ChinaCollege of Chemistry and Life Sciences, Beijing University of Technology, Beijing 100124, ChinaCollege of Chemistry and Life Sciences, Beijing University of Technology, Beijing 100124, ChinaCollege of Chemistry and Life Sciences, Beijing University of Technology, Beijing 100124, ChinaCollege of Chemistry and Life Sciences, Beijing University of Technology, Beijing 100124, ChinaCollege of Chemistry and Life Sciences, Beijing University of Technology, Beijing 100124, China<b>Background</b>: Wound healing is a complex and intricate biological process that involves multiple systems within the body and initiates a series of highly coordinated responses to repair damage and restore integrity and functionality. We previously identified that breathing hydrogen can significantly inhibit early inflammation, activate autologous stem cells, and promote the accumulation of extracellular matrix (ECM). However, the broader functions and downstream targets of hydrogen-induced ECM accumulation and tissue remodeling are unknown in the wound-healing process. <b>Methods</b>: Consequently, this thesis developed a hydrogen sustained-release dressing based on a micro storage material and reveals the mechanism of hydrogen in treating wound healing. Upon encapsulating the hydrogen storage materials, magnesium (Mg), and ammonia borane (AB), we found that SiO<sub>2</sub>@Mg exhibits superior sustained-release performance, while SiO<sub>2</sub>@AB demonstrates a higher hydrogen storage capacity. We used a <i>C57/BL6</i> mouse full-thickness skin defect wound model to analyze and compare different hydrogen dressings. <b>Results</b>: It was identified that hydrogen dressings can significantly improve the healing rate of wounds by promoting epithelialization, angiogenesis, and collagen accumulation in wound tissue, and that the effect of slow-release dressings is better than of non-slow-release dressings. We also found that hydrogen dressing can promote transcriptome-level expression related to cell proliferation and differentiation and ECM accumulation, mainly through the <i>Wnt1/β-catenin</i> pathway and <i>TGF-β1/Smad2</i> pathway. <b>Conclusions</b>: Overall, these results provide a novel insight into the field of hydrogen treatment and wound healing.https://www.mdpi.com/1999-4923/17/3/279wound healinghydrogen-releasing micromaterialextracellular matrix depositionangiogenesismolecular mechanism
spellingShingle Pengxiang Zhao
Yufei Li
Boyuan Guo
Ziyi Liu
Xujuan Zhang
Mengyu Liu
Xuemei Ma
Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways
Pharmaceutics
wound healing
hydrogen-releasing micromaterial
extracellular matrix deposition
angiogenesis
molecular mechanism
title Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways
title_full Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways
title_fullStr Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways
title_full_unstemmed Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways
title_short Hydrogen-Releasing Micromaterial Dressings: Promoting Wound Healing by Modulating Extracellular Matrix Accumulation Through Wnt/β-Catenin and TGF-β/Smad Pathways
title_sort hydrogen releasing micromaterial dressings promoting wound healing by modulating extracellular matrix accumulation through wnt β catenin and tgf β smad pathways
topic wound healing
hydrogen-releasing micromaterial
extracellular matrix deposition
angiogenesis
molecular mechanism
url https://www.mdpi.com/1999-4923/17/3/279
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