Inflammation-Responsive Hydrogel Accelerates Diabetic Wound Healing through Immunoregulation and Enhanced Angiogenesis

Adv Healthc Mater. 2025 Feb;14(5):e2400150. doi: 10.1002/adhm.202400150. Epub 2024 May 5.

Abstract

Angiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation-responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co-loaded hydrogel is biocompatible and possesses effective anti-inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.

Keywords: angiogenesis; bioresponsive hydrogel; chronic wounds; drug delivery.

MeSH terms

  • Angiogenesis
  • Animals
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / pathology
  • Ferrocyanides / chemistry
  • Ferrocyanides / pharmacology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • Neovascularization, Physiologic* / drug effects
  • Oxidative Stress / drug effects
  • Vascular Endothelial Growth Factor A / pharmacology
  • Wound Healing* / drug effects

Substances

  • Hydrogels
  • Vascular Endothelial Growth Factor A
  • Ferrocyanides
  • ferric ferrocyanide