Effect of genipin crosslinked chitosan scaffolds containing SDF-1 on wound healing in a rat model

Mater Sci Eng C Mater Biol Appl. 2020 Apr:109:110368. doi: 10.1016/j.msec.2019.110368. Epub 2019 Dec 6.

Abstract

Prolonged healing is a severe problem for elderly and diabetic patients. Impaired angiogenesis, stem cell differentiation, and migration have been shown to delay wound healing. The chemokine stromal cell-derived factor-1 (SDF-1) plays an essential role in recruiting cells to wound sites and is suggested to be a candidate for tissue engineering. In this study, chitosan (CHI) scaffolds were crosslinked with nontoxic genipin (Gp) and further heparinized for SDF-1 immobilization. Then, the structures were evaluated for their physicochemical properties (porosity, swelling ratio, and water vapor transmission rate (WVTR)). The interaction between SDF-1 and heparin could sustain SDF-1 release, which has been shown to enhance human umbilical vein endothelial cell (HUVEC) 2D/3D migration. The investigation of the wound-healing activity of the SDF-1-loaded CHI scaffolds revealed a better wound recovery rate in vivo in healthy and streptozotocin-induced diabetic Sprague-Dawley (SD) rats. The histological analysis illustrated that the local of SDF-1 treatment scaffold at the wound site enhanced neovascularization. The wounds treated with SDF-1 scaffolds also exhibited higher vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) expression in Western blot assays. Based on the wound-healing activity and beneficial characteristics, the SDF-1-loaded CHI scaffold demonstrates potential as a material for treating skin wounds.

Keywords: Chitosan; Genipin; Stromal cell-derived factor-1 (SDF-1); VEGF; Wound healing.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Movement / physiology
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism*
  • Chitosan / chemistry*
  • Collagen / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Iridoids / chemistry*
  • Male
  • Porosity
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / toxicity
  • Tissue Scaffolds / chemistry*
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Iridoids
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Streptozocin
  • Collagen
  • Chitosan
  • genipin