Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing

Nitric oxide (NO) is an endogenous signaling molecule that plays a critical role in wound healing. However, the gaseous nature, short half-life, and low stability of NO present challenges for its clinical application. To address these issues, this study introduces an innovative S-nitrosoglutathione...

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Main Authors: Jiafeng Tan, Minna Wen, Yifan Zhang, Shuyun Zhang, Min Fang, Junxiao Xiang, Xinshuo Liu, Jinhuan Tian, Lu Lu, Binghong Luo, Changren Zhou, Lihua Li
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Gels
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Online Access:https://www.mdpi.com/2310-2861/11/5/354
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author Jiafeng Tan
Minna Wen
Yifan Zhang
Shuyun Zhang
Min Fang
Junxiao Xiang
Xinshuo Liu
Jinhuan Tian
Lu Lu
Binghong Luo
Changren Zhou
Lihua Li
author_facet Jiafeng Tan
Minna Wen
Yifan Zhang
Shuyun Zhang
Min Fang
Junxiao Xiang
Xinshuo Liu
Jinhuan Tian
Lu Lu
Binghong Luo
Changren Zhou
Lihua Li
author_sort Jiafeng Tan
collection DOAJ
description Nitric oxide (NO) is an endogenous signaling molecule that plays a critical role in wound healing. However, the gaseous nature, short half-life, and low stability of NO present challenges for its clinical application. To address these issues, this study introduces an innovative S-nitrosoglutathione (GSNO)-loaded asymmetric alginate (SA) hydrogel (GSNO-SA) as a novel solution for treating infected chronic wounds. The hydrogel is designed with a layer-by-layer melting-permeation crosslinking approach, forming a dense upper layer and a sparse lower layer structure, effectively promoting exudate management while delaying NO release. The results demonstrate that the GSNO-SA hydrogel extends NO release for up to 48 h, exhibits rapid exudate absorption (72.3 ± 1.5% equilibrium swelling after 5 min), significant antibacterial activity (over 90% antibacterial rate against <i>E. coli</i> and <i>S. aureus</i>), and anti-inflammatory effects (marked reduction in TNF-α expression), and promotes angiogenesis (90.00 ± 5.92% migration rate at 48 h). Additionally, animal studies show that the GSNO-SA hydrogel accelerates wound healing, achieving a 99.2 ± 0.1% closure rate at 14 days. Histological and immunohistochemical evaluations further confirm its ability to regulate inflammation (13.34-fold upregulation of CD163) and promote angiogenesis (3.02-fold upregulation of α-SMA). Theoretically, this asymmetric design provides a novel strategy for developing exudate-managing dressings by integrating controlled NO release with hierarchical pore structures.
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spelling doaj-art-d5998f02e1da4c4284a1e4cb696ac0182025-08-20T02:33:56ZengMDPI AGGels2310-28612025-05-0111535410.3390/gels11050354Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound HealingJiafeng Tan0Minna Wen1Yifan Zhang2Shuyun Zhang3Min Fang4Junxiao Xiang5Xinshuo Liu6Jinhuan Tian7Lu Lu8Binghong Luo9Changren Zhou10Lihua Li11Engineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaCollege of Public Security and Traffic Management, Guangdong Police College, Guangzhou 510440, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaEngineering Research Center of Artificial Organs and Materials, College of Chemistry and Materials, Jinan University, Guangzhou 510632, ChinaNitric oxide (NO) is an endogenous signaling molecule that plays a critical role in wound healing. However, the gaseous nature, short half-life, and low stability of NO present challenges for its clinical application. To address these issues, this study introduces an innovative S-nitrosoglutathione (GSNO)-loaded asymmetric alginate (SA) hydrogel (GSNO-SA) as a novel solution for treating infected chronic wounds. The hydrogel is designed with a layer-by-layer melting-permeation crosslinking approach, forming a dense upper layer and a sparse lower layer structure, effectively promoting exudate management while delaying NO release. The results demonstrate that the GSNO-SA hydrogel extends NO release for up to 48 h, exhibits rapid exudate absorption (72.3 ± 1.5% equilibrium swelling after 5 min), significant antibacterial activity (over 90% antibacterial rate against <i>E. coli</i> and <i>S. aureus</i>), and anti-inflammatory effects (marked reduction in TNF-α expression), and promotes angiogenesis (90.00 ± 5.92% migration rate at 48 h). Additionally, animal studies show that the GSNO-SA hydrogel accelerates wound healing, achieving a 99.2 ± 0.1% closure rate at 14 days. Histological and immunohistochemical evaluations further confirm its ability to regulate inflammation (13.34-fold upregulation of CD163) and promote angiogenesis (3.02-fold upregulation of α-SMA). Theoretically, this asymmetric design provides a novel strategy for developing exudate-managing dressings by integrating controlled NO release with hierarchical pore structures.https://www.mdpi.com/2310-2861/11/5/354S-nitrosoglutathioneasymmetrical hydrogelsodium alginatechronic woundsinfectious wounds
spellingShingle Jiafeng Tan
Minna Wen
Yifan Zhang
Shuyun Zhang
Min Fang
Junxiao Xiang
Xinshuo Liu
Jinhuan Tian
Lu Lu
Binghong Luo
Changren Zhou
Lihua Li
Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing
Gels
S-nitrosoglutathione
asymmetrical hydrogel
sodium alginate
chronic wounds
infectious wounds
title Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing
title_full Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing
title_fullStr Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing
title_full_unstemmed Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing
title_short Development of an Asymmetric Alginate Hydrogel Loaded with S-Nitrosoglutathione and Its Application in Chronic Wound Healing
title_sort development of an asymmetric alginate hydrogel loaded with s nitrosoglutathione and its application in chronic wound healing
topic S-nitrosoglutathione
asymmetrical hydrogel
sodium alginate
chronic wounds
infectious wounds
url https://www.mdpi.com/2310-2861/11/5/354
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