Calcium ion cross-linked sodium alginate hydrogels containing deferoxamine and copper nanoparticles for diabetic wound healing

Shengbo Li, Xuemei Wang, Jing Chen, Jiahe Guo, Meng Yuan, Gui Wan, Chengqi Yan, Wenqing Li, Hans Günther Machens, Yuval Rinkevich, Xiaofan Yang, Heng Song, Zhenbing Chen

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Chronic non-healing diabetic wounds and ulcers can be fatal, lead to amputations, and remain a major challenge to medical, and health care sectors. Susceptibility to infection and impaired angiogenesis are two central reasons for the clinical consequences associated with chronic non-healing diabetic wounds. Herein, we successfully developed calcium ion (Ca2+) cross-linked sodium alginate (SA) hydrogels with both pro-angiogenesis and antibacterial properties. Our results demonstrated that deferoxamine (DFO) and copper nanoparticles (Cu-NPs) worked synergistically to enhance the proliferation, migration, and angiogenesis of human umbilical venous endothelial cells in vitro. Results of colony formation assay indicated Cu-NPs were effective against E. coli and S. aureus in a dose-dependent manner in vitro. An SA hydrogel containing both DFO and Cu-NPs (SA-DFO/Cu) was prepared using a Ca2+ cross-linking method. Cytotoxicity assay and colony formation assay indicated that the hydrogel exhibited beneficial biocompatible and antibacterial properties in vitro. Furthermore, SA-DFO/Cu significantly accelerated diabetic wound healing, improved angiogenesis and reduced long-lasting inflammation in a mouse model of diabetic wound. Mechanistically, DFO and Cu-NPs synergistically stimulated the levels of hypoxia-inducible factor 1α and vascular endothelial growth factor in vivo. Given the pro-angiogenesis, antibacterial and healing properties, the hydrogel possesses high potential for clinical application in refractory wounds.

Original languageEnglish
Pages (from-to)657-670
Number of pages14
JournalInternational Journal of Biological Macromolecules
Volume202
DOIs
StatePublished - 31 Mar 2022

Keywords

  • Copper nanoparticles
  • Deferoxamine
  • Diabetic wound
  • Hydrogel

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