Enhanced diabetic wound healing with injectable hydrogel containing self-assembling nanozymes

J Control Release. 2024 Aug:372:265-280. doi: 10.1016/j.jconrel.2024.06.040. Epub 2024 Jun 24.

Abstract

To build a smart system in response to the variable microenvironment in infected diabetic wounds, a multifunctional wound dressing was constructed by co-incorporating glucose oxidase (GOx) and a pH-responsive self-assembly Cu2-xSe-BSA nanozyme into a dual-dynamic bond cross-linked hydrogel (OBG). This composite hydrogel (OBG@CG) can adhere to the wound site and respond to the acidic inflammatory environment, initiating the GOx-catalyzed generation of H2O2 and the self-assembly activated peroxidase-like property of Cu2-xSe-BSA nanozymes, resulting in significant hydroxyl radical production to attack the biofilm during the acute infection period and alleviate the high-glucose microenvironment for better wound healing. During the wound recovery phase, Cu2-xSe-BSA aggregates disassembled owing to the elevated pH, terminating catalytic reactive oxygen species generation. Simultaneously, Cu2+ released from the Cu2-xSe-BSA not only promotes the production of mature collagen but also enhances the migration and proliferation of endothelial cells. RNA-seq analysis demonstrated that OBG@CG exerted its antibacterial property by damaging the integrity of the biofilm by inducing radicals and interfering with the energy supply, along with destroying the defense system by disturbing thiol metabolism and reducing transporter activities. This work proposes an innovative glucose consumption strategy for infected diabetic wound management, which may inspire new ideas in the exploration of smart wound dressing.

Keywords: Defense system damage; Energy supply interference; Glucose consumption; Injectable self-healing hydrogel; Self-assembly activation.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Bandages
  • Biofilms / drug effects
  • Copper / administration & dosage
  • Copper / chemistry
  • Diabetes Mellitus, Experimental / drug therapy
  • Glucose Oxidase* / administration & dosage
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogels* / administration & dosage
  • Hydrogels* / chemistry
  • Hydrogen Peroxide
  • Male
  • Mice
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Wound Healing* / drug effects

Substances

  • Glucose Oxidase
  • Hydrogels
  • Anti-Bacterial Agents
  • Copper
  • Hydrogen Peroxide
  • Reactive Oxygen Species