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

  • Int J Biol Macromol. 2022 Mar 31;202:657-670. doi: 10.1016/j.ijbiomac.2022.01.080.
Shengbo Li  1 ,  Xuemei Wang  2 ,  Jing Chen  1 ,  Jiahe Guo  1 ,  Meng Yuan  1 ,  Gui Wan  1 ,  Chengqi Yan  1 ,  Wenqing Li  3 ,  Hans-Günther Machens  4 ,  Yuval Rinkevich  5 ,  Xiaofan Yang  6 ,  Heng Song  7 ,  Zhenbing Chen  8
Affiliations
  • 1. Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 2. College of Chemistry & Molecular Science, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University, Wuhan 430072, China.
  • 3. Department of Hand and Foot Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong, China.
  • 4. Department of Plastic and Hand Surgery, Technical University of Munich, Munich 81675, Germany.
  • 5. Institute of Lung Biology and Disease, Helmholtz Zentrum München, Max-Lebsche-Platz 31, 81377 Munich, Germany; Institute of Regenerative Biology and Medicine, Helmholtz Zentrum München, Max-Lebsche-Platz 31, 81377 Munich, Germany.
  • 6. Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: [email protected].
  • 7. College of Chemistry & Molecular Science, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University, Wuhan 430072, China. Electronic address: [email protected].
  • 8. Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: [email protected].
PMID: 35066024 DOI: 10.1016/j.ijbiomac.2022.01.080
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.

Keywords
Copper nanoparticles; Deferoxamine; Diabetic wound; Hydrogel.
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