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

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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.

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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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Author notes

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

Authors and Affiliations

  1. The State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu, 610065, China

    Zejun Xu & Guiting Liu

  2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Zejun Xu & Jun Wu

  3. Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, Life Science Institutes, Guangxi Medical University, Nanning, 530021, China

    Li Zheng

  4. 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

    Li Zheng

  5. Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, 511400, China

    Jun Wu

  6. Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, 999077, China

    Jun Wu

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  1. Zejun Xu
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  2. Guiting Liu
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  3. Li Zheng
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  4. Jun Wu
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Correspondence to Li Zheng or Jun Wu.

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

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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 Res. 16, 905–916 (2023). https://doi.org/10.1007/s12274-022-4792-6

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