Mechanisms of magnesium oxide-incorporated electrospun membrane modulating inflammation and accelerating wound healing
Mingyue Liu
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorWeixing Zhang
Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorZhe Chen
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorYangfan Ding
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorBinbin Sun
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorHongsheng Wang
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorXiumei Mo
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorCorresponding Author
Jinglei Wu
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Correspondence
Jinglei Wu, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
Email: [email protected]
Search for more papers by this authorMingyue Liu
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorWeixing Zhang
Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Search for more papers by this authorZhe Chen
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorYangfan Ding
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorBinbin Sun
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorHongsheng Wang
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorXiumei Mo
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Search for more papers by this authorCorresponding Author
Jinglei Wu
Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, China
Correspondence
Jinglei Wu, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, China.
Email: [email protected]
Search for more papers by this authorMingyue Liu and Weixing Zhang contributed equally to this work.
Funding information: National Natural Science Foundation of China, Grant/Award Number: 31900949; Science and Technology Commission of Shanghai Municipality, Grant/Award Numbers: 19440741300, 20DZ2254900
Abstract
Previously, we demonstrated that magnesium oxide (MgO)-incorporated electrospun membranes show powerful antibacterial activity and promote wound healing, but the underlying mechanisms have not been entirely understood. Herein, we investigated the relationship between structure and function of MgO-incorporated membranes and interrogated critical bioactive cues that contribute to accelerated wound healing and functional restoration. Our results show that MgO-incorporated membranes exhibit good flexibility and improved water vapor transmission rates (WVTRs) and sustained Mg2+ release in a simulated model of wounds. MgO-incorporated membranes modulate macrophage phenotype to downregulate inflammatory response, contributing to alleviated inflammation and creating a favorable microenvironment for wound healing. Specifically, MgO-incorporated membranes stimulate macrophages to shift to a pro-healing M2 phenotype and upregulate pro-healing cytokine of transforming growth factor-beta 1 (TGF-β1) and downregulate pro-inflammatory cytokines under lipopolysaccharide (LPS) challenge conditions. Together with increased TGF-β1 by macrophages, MgO-incorporated membranes significantly boost the proliferation of fibroblasts and upregulate collagen production, thus driving granulation tissue formation and wound closure. MgO-incorporated membranes promote angiogenesis by promoting tube formation and upregulating vascular endothelial growth factor (VEGF) production of endothelial cells. Rapid epithelialization of regenerated skin tissue is attributed to the balanced phenotype of keratinocytes between proliferative and terminally differentiated populations. In addition to coordinating keratinocyte phenotype, MgO-incorporated membranes reduce the expression of inflammatory cytokine interleukin 1-alpha (IL-1α) therefore promoting hair follicle regeneration. These data provide mechanisms of MgO-incorporated membranes that inhibit bacterial infection, alleviate inflammation, facilitate extracellular matrix production and epithelialization, and potentiate hair follicle regeneration.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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