In situ formed anti-inflammatory hydrogel loading plasmid DNA encoding VEGF for burn wound healing

Acta Biomater. 2019 Dec:100:191-201. doi: 10.1016/j.actbio.2019.10.004. Epub 2019 Oct 4.

Abstract

Excessive inflammation and reduced angiogenesis are two major obstacles in burn wound healing and skin regeneration. Here we report the fabrication and application of a sophisticated hydrogel from chemically modified hyaluronic acid (HA), dextran (Dex), and β-cyclodextrin (β-CD) integrating resveratrol (Res) and vascular endothelial growth factor (VEGF) plasmid as the anti-inflammatory and pro-angiogenic components for burn wounds. Firstly, covalent alterations were conducted to obtain methacrylic acid anhydride modified HA (HAMA), N-hydroxyethylacrylamide (HEAA) modified Dex (Dex-HEAA), and poly(ethylene glycol) methyl acrylate (526) modified β-CD (526-β-CD), respectively. Secondly, anti-inflammatory substance Res was embedded into the lipophilic central cavity of 526-β-CD to achieve a complex of 526-β-CD-Res. Then hydrogels with different HAMA, Dex-HEAA, and 526-β-CD-Res ratios were generated via UV irradiation. Lastly, plasmid DNA encoded with vascular endothelial growth factor (pDNA-VEGF) conjugating with polyethylenimine was loaded into the hydrogel scaffold. Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds. STATEMENT OF SIGNIFICANCE: Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds.

Keywords: Burn wound healing; Hydrogel; Resveratrol; Vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Biocompatible Materials / pharmacology
  • Burns / drug therapy*
  • Burns / pathology*
  • DNA / metabolism*
  • Dextrans / chemistry
  • Disease Models, Animal
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hyaluronic Acid / chemistry
  • Hydrogels / chemistry*
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Neovascularization, Physiologic / drug effects
  • Plasmids / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Resveratrol / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Wound Healing* / drug effects
  • beta-Cyclodextrins / chemistry

Substances

  • Anti-Inflammatory Agents
  • Biocompatible Materials
  • Dextrans
  • Hydrogels
  • Interleukin-1beta
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • beta-Cyclodextrins
  • Hyaluronic Acid
  • DNA
  • betadex
  • Resveratrol