A Guanosine-Quadruplex Hydrogel as Cascade Reaction Container Consuming Endogenous Glucose for Infected Wound Treatment-A Study in Diabetic Mice

Yuanfeng Li, Linzhu Su, Yongxin Zhang, Yong Liu*, Fan Huang*, Yijin Ren, Yingli An, Linqi Shi*, Henny C. van der Mei*, Henk J. Busscher

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Diabetic foot ulcers infected with antibiotic-resistant bacteria form a severe complication of diabetes. Antimicrobial-loaded hydrogels are used as a dressing for infected wounds, but the ongoing rise in the number of antimicrobial-resistant infections necessitates new, nonantibiotic based designs. Here, a guanosine-quadruplex (G(4))-hydrogel composed of guanosine, 2-formylphenylboronic acid, and putrescine is designed and used as a cascade-reaction container. The G(4)-hydrogel is loaded with glucose-oxidase and hemin. The first cascade-reaction, initiated by glucose-oxidase, transforms glucose and O-2 into gluconic acid and H2O2. In vitro, this reaction is most influential on killing Staphylococcus aureus or Pseudomonas aeruginosa in suspension, but showed limited killing of bacteria in biofilm-modes of growth. The second cascade-reaction, however, transforming H2O2 into reactive-oxygen-species (ROS), also enhances killing of biofilm bacteria due to hemin penetration into biofilms and interaction with eDNA G-quadruplexes in the biofilm matrix. Therewith, the second cascade-reaction generates ROS close to the target bacteria, facilitating killing despite the short life-time of ROS. Healing of infected wounds in diabetic mice proceeds faster upon coverage by these G(4)-hydrogels than by clinically common ciprofloxacin irrigation. Moreover, local glucose concentrations around infected wounds decrease. Concluding, a G(4)-hydrogel loaded with glucose-oxidase and hemin is a good candidate for infected wound dressings, particularly in diabetic patients.

Original languageEnglish
Article number2103485
Number of pages13
JournalAdvanced science
Issue number7
Early online date22-Jan-2022
Publication statusPublished - 4-Mar-2022


  • bacterial infection
  • cascade reactions
  • diabetic foot ulcers
  • reactive-oxygen-species
  • supramolecular hydrogels
  • DNA

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