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A universal gelation strategy of bivalent anions to construct nanofibrous lysozyme hydrogels for immunomemory anti-recurrence of diabetic wound infection by activating cGAS-STING pathway
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  • Aihui Wang,
  • Liqun Li,
  • Liqian Zheng,
  • Bang-Ping Jiang,
  • Yihao Liu,
  • Rimei Huang,
  • Huimin Qiu,
  • Shichen Ji,
  • Hong Liang,
  • Xing-Can Shen
Aihui Wang
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Liqun Li
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Liqian Zheng
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Bang-Ping Jiang
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources

Corresponding Author:[email protected]

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Yihao Liu
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Rimei Huang
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Huimin Qiu
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Shichen Ji
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Hong Liang
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Xing-Can Shen
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources
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Abstract

Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity, excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme-nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme-based hydrogels. Specially, divalent anions are found to universally drive LZF for the aggregation and transformation into three-dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near infrared light-mediated photothermal characteristics are endowed for LZF to enhance its inhibitory activity of multi-drug-resistant bacteria by the skeleton modification with genipin to produce genipin-conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO 4-crosslinked GLZF hydrogel is constructed to sensitize cGAS-STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the infected anti-recurrence of diabetic wound via photo-enhanced bacterial killing and cGAS-STING pathway. Thereby, it paves the way to employ the universal divalent anion-mediated gelation strategy for future developing functional inorganic salt-hybrided lysozyme hydrogels.
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