Bifunctional copper ion/melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healing

Skin infections present a major clinical challenge, as bacterial invasion and inflammation can complicate wound healing. Therefore, bacterial infections must be treated while the accompanying inflammation and oxidative stress are regulated. Owing to the ongoing global increase in bacterial resistanc...

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Main Authors: Jun Yao, Xiao Li, Minjie Lin, Zhuoqi Han, Xiaonan Wang, Jingjing Guo, Bing Wu, Jiajie Xia
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Materials & Design
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Online Access:http://www.sciencedirect.com/science/article/pii/S0264127525000516
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author Jun Yao
Xiao Li
Minjie Lin
Zhuoqi Han
Xiaonan Wang
Jingjing Guo
Bing Wu
Jiajie Xia
author_facet Jun Yao
Xiao Li
Minjie Lin
Zhuoqi Han
Xiaonan Wang
Jingjing Guo
Bing Wu
Jiajie Xia
author_sort Jun Yao
collection DOAJ
description Skin infections present a major clinical challenge, as bacterial invasion and inflammation can complicate wound healing. Therefore, bacterial infections must be treated while the accompanying inflammation and oxidative stress are regulated. Owing to the ongoing global increase in bacterial resistance, in this study, hydrogel co-loaded with bio-antimicrobial peptides and copper ions is designed, which exhibits antimicrobial, anti-inflammatory, and antioxidant properties. the proposed, sodium alginate@copper hydrogel (SA@Cu) is formed through the cross-linking of sodium alginate and Cu2+. Melittin (MEL) is then loaded to prepare a SA@Cu-MEL hydrogel. We optimised the sodium alginate and Cu2+ and MEL concentrations in SA@Cu-MEL hydrogels using Response Surface Methodology method. The proposed SA@Cu-MEL hydrogel exhibits significant antibacterial activity against Staphylococcus aureus and Escherichia coli, as well as good mechanical properties, self-healing ability, and MEL slow-release behaviour. Additionally, the SA@Cu-MEL hydrogel reduces inflammatory responses, promotes macrophage polarisation to the anti-inflammatory M2 type, and facilitates NIH cell proliferation and migration. In rat models, SA@Cu-MEL significantly accelerated wound healing, enhancing angiogenesis and collagen deposition. The optimised hydrogel not only reduces MEL toxicity but also amplifies its antibacterial and anti-inflammatory effects. Therefore, the proposed hydrogel has promising potential application in the treatment of infected skin wounds.
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spelling doaj-art-19f2466924c742f2b94a7c6982e070802025-01-20T04:17:16ZengElsevierMaterials & Design0264-12752025-02-01250113631Bifunctional copper ion/melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healingJun Yao0Xiao Li1Minjie Lin2Zhuoqi Han3Xiaonan Wang4Jingjing Guo5Bing Wu6Jiajie Xia7Department of Orthopedic Surgery, Shaoxing Central Hospital, The Central Affiliated Hospital, Shaoxing University 312030 ChinaThe Second Clinical Medical College, Zhejiang Chinese Medical University 310053 ChinaDepartment of General Surgery, Shaoxing Central Hospital, The Central Affiliated Hospital, Shaoxing University 312030 ChinaDepartment of Surgical Oncology, The First Affiliated Hospital of Bengbu, Medical University 233030 ChinaDepartment of Pharmacy, Shaoxing Central Hospital, The Central Affiliated Hospital, Shaoxing University 312030 ChinaDepartment of Pharmacy, Shaoxing Central Hospital, The Central Affiliated Hospital, Shaoxing University 312030 ChinaDepartment of Orthopedic Surgery, Shaoxing Central Hospital, The Central Affiliated Hospital, Shaoxing University 312030 China; Corresponding authors.Department of Neurosurgery, Shaoxing Central Hospital, The Central Affiliated Hospital, Shaoxing University 312030 China; Corresponding authors.Skin infections present a major clinical challenge, as bacterial invasion and inflammation can complicate wound healing. Therefore, bacterial infections must be treated while the accompanying inflammation and oxidative stress are regulated. Owing to the ongoing global increase in bacterial resistance, in this study, hydrogel co-loaded with bio-antimicrobial peptides and copper ions is designed, which exhibits antimicrobial, anti-inflammatory, and antioxidant properties. the proposed, sodium alginate@copper hydrogel (SA@Cu) is formed through the cross-linking of sodium alginate and Cu2+. Melittin (MEL) is then loaded to prepare a SA@Cu-MEL hydrogel. We optimised the sodium alginate and Cu2+ and MEL concentrations in SA@Cu-MEL hydrogels using Response Surface Methodology method. The proposed SA@Cu-MEL hydrogel exhibits significant antibacterial activity against Staphylococcus aureus and Escherichia coli, as well as good mechanical properties, self-healing ability, and MEL slow-release behaviour. Additionally, the SA@Cu-MEL hydrogel reduces inflammatory responses, promotes macrophage polarisation to the anti-inflammatory M2 type, and facilitates NIH cell proliferation and migration. In rat models, SA@Cu-MEL significantly accelerated wound healing, enhancing angiogenesis and collagen deposition. The optimised hydrogel not only reduces MEL toxicity but also amplifies its antibacterial and anti-inflammatory effects. Therefore, the proposed hydrogel has promising potential application in the treatment of infected skin wounds.http://www.sciencedirect.com/science/article/pii/S0264127525000516Sodium alginate-copper based hydrogelMelittinAntibacterialAnti-inflammatorySkin healing
spellingShingle Jun Yao
Xiao Li
Minjie Lin
Zhuoqi Han
Xiaonan Wang
Jingjing Guo
Bing Wu
Jiajie Xia
Bifunctional copper ion/melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healing
Materials & Design
Sodium alginate-copper based hydrogel
Melittin
Antibacterial
Anti-inflammatory
Skin healing
title Bifunctional copper ion/melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healing
title_full Bifunctional copper ion/melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healing
title_fullStr Bifunctional copper ion/melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healing
title_full_unstemmed Bifunctional copper ion/melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healing
title_short Bifunctional copper ion/melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healing
title_sort bifunctional copper ion melittin incorporated hydrogel with antimicrobial and antioxidant capabilities for infected skin wound healing
topic Sodium alginate-copper based hydrogel
Melittin
Antibacterial
Anti-inflammatory
Skin healing
url http://www.sciencedirect.com/science/article/pii/S0264127525000516
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