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Nano Research 2023, 16(1): 905-916 https://doi.org/10.1007/s12274-022-4792-6
Research Article | Issue | Published: 17 August 2022

A polyphenol-modified chitosan hybrid hydrogel with enhanced antimicrobial and antioxidant activities for rapid healing of diabetic wounds

Show Author's Information Zejun Xu1,2,§,  Guiting Liu1,§,  Li Zheng3,4( ),  Jun Wu2,5,6( )
The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, China
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, Life Science Institutes, Guangxi Medical University, Nanning 530021, China
Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning 530021, China
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511400, China
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China

§ Zejun Xu and Guiting Liu contributed equally to this work.

Keywords:
antioxidant, hydrogel, antimicrobial, diabetic wound
Topics:
Medical imaging
Cite this article:
Xu Z, Liu G, Zheng L, et al. A polyphenol-modified chitosan hybrid hydrogel with enhanced antimicrobial and antioxidant activities for rapid healing of diabetic wounds. Nano Research, 2023, 16(1): 905-916. https://doi.org/10.1007/s12274-022-4792-6
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Abstract Full text Electronic supplementary material About this article

High oxidative stress injury and bacterial infection are the main challenges that impair wound healing in diabetic patients. Therefore, a hydrogel with enhanced antimicrobial and antioxidant properties was developed for rapid healing of diabetic wounds. In this study, chitosan methacrylate-gallic acid (CSMA-GA) polymer with antioxidant activity, antimicrobial activity, and ultraviolet (UV)-triggered gelling properties was developed as a hydrogel precursor. Meanwhile, amphiphilic Pluronic F127 molecules were used to load hydrophobic chlorhexidine drug molecules to obtain F127/chlorhexidine nanoparticle (NP) with strong antibacterial activity. Subsequently, F127/chlorhexidine NPs were encapsulated in CSMA-GA hydrogel to further enhance its antibacterial activity. The hybrid hydrogel platform (CSMA-GA/F127/chlorhexidine (CMGFC)) exhibited high antibacterial efficiency (> 99.9%) and strong reactive oxygen species (ROS) scavenging ability (> 80.0%), which effectively protected cells from external oxidative stress (upregulated superoxide dismutase (SOD) and glutathione/oxidized glutathione disulfide (GSH/GSSG) levels and downregulated malondialdehyde (MDA) levels). Moreover, in vivo results proved that the CMGFC hydrogel significantly reduced inflammatory responses (downregulated interleukin-6 (IL-6) and upregulated interleukin-10 (IL-10) levels), promoted angiogenesis (upregulated vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD 31) levels), and wound healing (enhanced collagen deposition and tissue remodelling). Overall, the CMGFC hydrogel with enhanced antimicrobial and antioxidant properties demonstrated significant potential to enhance diabetic wound healing.


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Abstract
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Electronic supplementary material
About this article

A polyphenol-modified chitosan hybrid hydrogel with enhanced antimicrobial and antioxidant activities for rapid healing of diabetic wounds

Show Author's information Zejun Xu1,2,§, Guiting Liu1,§, Li Zheng3,4( ), Jun Wu2,5,6( )
The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, China
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, Life Science Institutes, Guangxi Medical University, Nanning 530021, China
Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning 530021, China
Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou 511400, China
Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China

§ Zejun Xu and Guiting Liu contributed equally to this work.

Abstract

High oxidative stress injury and bacterial infection are the main challenges that impair wound healing in diabetic patients. Therefore, a hydrogel with enhanced antimicrobial and antioxidant properties was developed for rapid healing of diabetic wounds. In this study, chitosan methacrylate-gallic acid (CSMA-GA) polymer with antioxidant activity, antimicrobial activity, and ultraviolet (UV)-triggered gelling properties was developed as a hydrogel precursor. Meanwhile, amphiphilic Pluronic F127 molecules were used to load hydrophobic chlorhexidine drug molecules to obtain F127/chlorhexidine nanoparticle (NP) with strong antibacterial activity. Subsequently, F127/chlorhexidine NPs were encapsulated in CSMA-GA hydrogel to further enhance its antibacterial activity. The hybrid hydrogel platform (CSMA-GA/F127/chlorhexidine (CMGFC)) exhibited high antibacterial efficiency (> 99.9%) and strong reactive oxygen species (ROS) scavenging ability (> 80.0%), which effectively protected cells from external oxidative stress (upregulated superoxide dismutase (SOD) and glutathione/oxidized glutathione disulfide (GSH/GSSG) levels and downregulated malondialdehyde (MDA) levels). Moreover, in vivo results proved that the CMGFC hydrogel significantly reduced inflammatory responses (downregulated interleukin-6 (IL-6) and upregulated interleukin-10 (IL-10) levels), promoted angiogenesis (upregulated vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD 31) levels), and wound healing (enhanced collagen deposition and tissue remodelling). Overall, the CMGFC hydrogel with enhanced antimicrobial and antioxidant properties demonstrated significant potential to enhance diabetic wound healing.

Keywords: antioxidant, hydrogel, antimicrobial, diabetic wound

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Publication history
Copyright
Acknowledgements

Publication history

Received: 20 June 2022
Revised: 17 July 2022
Accepted: 18 July 2022
Published: 17 August 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 51973243), Fundamental Research Funds for the Central Universities (No. 191gzd35), Guangdong Innovative and Entrepreneurial Research Team Program (No. 2016ZT06S029), Shenzhen Basic Research Project (No. JCYJ20190807155801657), and Key international (regional) cooperative research projects of the National Natural Science Foundation of China (No. 5181001045).

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