Insulin/PHMB-grafted sodium alginate hydrogels improve infected wound healing by antibacterial-prompted macrophage inflammatory regulation

Abstract Background Non-healing chronic wounds with high susceptibility to infection represent a critical challenge in modern healthcare. While growth factors play a pivotal role in regulating chronic wound repair, their therapeutic efficacy is compromised in infected microenvironments. Current woun...

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Main Authors: Dan Liu, Tianyi Yu, Shan Ma, Lefeng Su, Shan Zhong, Wenao Wang, Yang Liu, Jia-ao Yu, Min Gao, Yunsheng Chen, He Xu, Yan Liu
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03398-8
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author Dan Liu
Tianyi Yu
Shan Ma
Lefeng Su
Shan Zhong
Wenao Wang
Yang Liu
Jia-ao Yu
Min Gao
Yunsheng Chen
He Xu
Yan Liu
author_facet Dan Liu
Tianyi Yu
Shan Ma
Lefeng Su
Shan Zhong
Wenao Wang
Yang Liu
Jia-ao Yu
Min Gao
Yunsheng Chen
He Xu
Yan Liu
author_sort Dan Liu
collection DOAJ
description Abstract Background Non-healing chronic wounds with high susceptibility to infection represent a critical challenge in modern healthcare. While growth factors play a pivotal role in regulating chronic wound repair, their therapeutic efficacy is compromised in infected microenvironments. Current wound dressings inadequately address the dual demands of sustained bioactive molecule delivery and robust antimicrobial activity. Results In this study, we developed a sodium alginate hydrogel (termed P-SA/Ins), which incorporated polyhexamethylene biguanide (PHMB) grafting and long-acting glargine insulin loading. P-SA/Ins exhibited the favorable physicochemical performance, biocompatibility and antibacterial efficacy against both Gram-negative and Gram-positive pathogens through inhibition of bacterial proliferation and biofilm formation. Glargine insulin was applied to prolonged insulin delivery. P-SA/Ins treatment attenuated S. aureus induced pro-inflammatory cytokine cascades in macrophages. The evaluation in vivo using a rat model with S. aureus infected wound demonstrated that P-SA/Ins significantly enhanced wound healing and optimized skin barrier through antimicrobial-mediated modulation of macrophage polarization and subsequent inflammatory cytokine profiling. Conclusions Our findings demonstrate that P-SA/Ins promotes wound healing and restores epidermal barrier integrity, indicating its potential as a therapeutic dressing for chronic wound healing, particularly in cases with infection risk. Graphical abstract
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spelling doaj-art-37db85ed8d784d0b8d5011ef80016f282025-08-20T02:11:11ZengBMCJournal of Nanobiotechnology1477-31552025-05-0123111610.1186/s12951-025-03398-8Insulin/PHMB-grafted sodium alginate hydrogels improve infected wound healing by antibacterial-prompted macrophage inflammatory regulationDan Liu0Tianyi Yu1Shan Ma2Lefeng Su3Shan Zhong4Wenao Wang5Yang Liu6Jia-ao Yu7Min Gao8Yunsheng Chen9He Xu10Yan Liu11Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineCollege of Chemistry & Materials Science, Shanghai Normal UniversityDepartment of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Pediatric Urology, Xinhua Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineCollege of Chemistry & Materials Science, Shanghai Normal UniversityDepartment of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAbstract Background Non-healing chronic wounds with high susceptibility to infection represent a critical challenge in modern healthcare. While growth factors play a pivotal role in regulating chronic wound repair, their therapeutic efficacy is compromised in infected microenvironments. Current wound dressings inadequately address the dual demands of sustained bioactive molecule delivery and robust antimicrobial activity. Results In this study, we developed a sodium alginate hydrogel (termed P-SA/Ins), which incorporated polyhexamethylene biguanide (PHMB) grafting and long-acting glargine insulin loading. P-SA/Ins exhibited the favorable physicochemical performance, biocompatibility and antibacterial efficacy against both Gram-negative and Gram-positive pathogens through inhibition of bacterial proliferation and biofilm formation. Glargine insulin was applied to prolonged insulin delivery. P-SA/Ins treatment attenuated S. aureus induced pro-inflammatory cytokine cascades in macrophages. The evaluation in vivo using a rat model with S. aureus infected wound demonstrated that P-SA/Ins significantly enhanced wound healing and optimized skin barrier through antimicrobial-mediated modulation of macrophage polarization and subsequent inflammatory cytokine profiling. Conclusions Our findings demonstrate that P-SA/Ins promotes wound healing and restores epidermal barrier integrity, indicating its potential as a therapeutic dressing for chronic wound healing, particularly in cases with infection risk. Graphical abstracthttps://doi.org/10.1186/s12951-025-03398-8Infected wound healingInsulinPHMBInflammation regulationSkin barrier
spellingShingle Dan Liu
Tianyi Yu
Shan Ma
Lefeng Su
Shan Zhong
Wenao Wang
Yang Liu
Jia-ao Yu
Min Gao
Yunsheng Chen
He Xu
Yan Liu
Insulin/PHMB-grafted sodium alginate hydrogels improve infected wound healing by antibacterial-prompted macrophage inflammatory regulation
Journal of Nanobiotechnology
Infected wound healing
Insulin
PHMB
Inflammation regulation
Skin barrier
title Insulin/PHMB-grafted sodium alginate hydrogels improve infected wound healing by antibacterial-prompted macrophage inflammatory regulation
title_full Insulin/PHMB-grafted sodium alginate hydrogels improve infected wound healing by antibacterial-prompted macrophage inflammatory regulation
title_fullStr Insulin/PHMB-grafted sodium alginate hydrogels improve infected wound healing by antibacterial-prompted macrophage inflammatory regulation
title_full_unstemmed Insulin/PHMB-grafted sodium alginate hydrogels improve infected wound healing by antibacterial-prompted macrophage inflammatory regulation
title_short Insulin/PHMB-grafted sodium alginate hydrogels improve infected wound healing by antibacterial-prompted macrophage inflammatory regulation
title_sort insulin phmb grafted sodium alginate hydrogels improve infected wound healing by antibacterial prompted macrophage inflammatory regulation
topic Infected wound healing
Insulin
PHMB
Inflammation regulation
Skin barrier
url https://doi.org/10.1186/s12951-025-03398-8
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