Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways

Abstract Delayed wound healing remains a challenge, and macrophages play an important role in the inflammatory process of wound healing. Morphological changes in macrophages can affect their phenotype, but little is known about the underlying mechanism. Aligned electrospun nanofibers have natural ad...

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Main Authors: Jian Xie, Xiaowei Wu, Shang Zheng, Kaili Lin, Jiansheng Su
Format: Article
Language:English
Published: BMC 2022-07-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-022-01549-9
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author Jian Xie
Xiaowei Wu
Shang Zheng
Kaili Lin
Jiansheng Su
author_facet Jian Xie
Xiaowei Wu
Shang Zheng
Kaili Lin
Jiansheng Su
author_sort Jian Xie
collection DOAJ
description Abstract Delayed wound healing remains a challenge, and macrophages play an important role in the inflammatory process of wound healing. Morphological changes in macrophages can affect their phenotype, but little is known about the underlying mechanism. Aligned electrospun nanofibers have natural advantages in modulating cell morphology. Therefore, the current study constructed aligned electrospun nanofibers that could transform macrophages into elongated shapes. Our results demonstrated that aligned nanofibers without exogenous cytokines could downregulate the proinflammatory M1 phenotype and upregulate the prohealing M2 phenotype in an inflammatory environment. Importantly, our study revealed that aligned electrospun nanofibers could inhibit macrophage M1 polarization via the JAK-STAT and NF-κB pathways. Furthermore, the conditioned medium from macrophages cultured on aligned nanofibers could encourage fibroblast migration, proliferation and collagen secretion. In vivo, aligned nanofibers alleviated the inflammatory microenvironment, promoted angiogenesis and accelerated wound healing in mouse skin defects by modulating macrophage phenotypes. Collectively, aligned electrospun nanofibers can influence macrophage polarization via the JAK-STAT and NF-κB pathways and attenuate the local inflammatory response in skin wounds. This study provides a potential strategy to modulate macrophage polarization and promote wound healing by controlling the topology of biomaterials and offers a new perspective for the application of nanotechnology in wound healing.
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spelling doaj.art-8eea6bc0845f4c3eab189ba34225ebe62022-12-22T03:10:44ZengBMCJournal of Nanobiotechnology1477-31552022-07-0120111610.1186/s12951-022-01549-9Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathwaysJian Xie0Xiaowei Wu1Shang Zheng2Kaili Lin3Jiansheng Su4Department of Prosthodontics, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and RegenerationDepartment of Orthodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and RegenerationDepartment of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral DiseasesDepartment of Prosthodontics, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and RegenerationAbstract Delayed wound healing remains a challenge, and macrophages play an important role in the inflammatory process of wound healing. Morphological changes in macrophages can affect their phenotype, but little is known about the underlying mechanism. Aligned electrospun nanofibers have natural advantages in modulating cell morphology. Therefore, the current study constructed aligned electrospun nanofibers that could transform macrophages into elongated shapes. Our results demonstrated that aligned nanofibers without exogenous cytokines could downregulate the proinflammatory M1 phenotype and upregulate the prohealing M2 phenotype in an inflammatory environment. Importantly, our study revealed that aligned electrospun nanofibers could inhibit macrophage M1 polarization via the JAK-STAT and NF-κB pathways. Furthermore, the conditioned medium from macrophages cultured on aligned nanofibers could encourage fibroblast migration, proliferation and collagen secretion. In vivo, aligned nanofibers alleviated the inflammatory microenvironment, promoted angiogenesis and accelerated wound healing in mouse skin defects by modulating macrophage phenotypes. Collectively, aligned electrospun nanofibers can influence macrophage polarization via the JAK-STAT and NF-κB pathways and attenuate the local inflammatory response in skin wounds. This study provides a potential strategy to modulate macrophage polarization and promote wound healing by controlling the topology of biomaterials and offers a new perspective for the application of nanotechnology in wound healing.https://doi.org/10.1186/s12951-022-01549-9Aligned nanofibersMacrophage polarizationInflammationWound healingJAK-STATNF-κB
spellingShingle Jian Xie
Xiaowei Wu
Shang Zheng
Kaili Lin
Jiansheng Su
Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways
Journal of Nanobiotechnology
Aligned nanofibers
Macrophage polarization
Inflammation
Wound healing
JAK-STAT
NF-κB
title Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways
title_full Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways
title_fullStr Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways
title_full_unstemmed Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways
title_short Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways
title_sort aligned electrospun poly l lactide nanofibers facilitate wound healing by inhibiting macrophage m1 polarization via the jak stat and nf κb pathways
topic Aligned nanofibers
Macrophage polarization
Inflammation
Wound healing
JAK-STAT
NF-κB
url https://doi.org/10.1186/s12951-022-01549-9
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AT shangzheng alignedelectrospunpolyllactidenanofibersfacilitatewoundhealingbyinhibitingmacrophagem1polarizationviathejakstatandnfkbpathways
AT kaililin alignedelectrospunpolyllactidenanofibersfacilitatewoundhealingbyinhibitingmacrophagem1polarizationviathejakstatandnfkbpathways
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