Polynucleotide and Hyaluronic Acid Mixture for Skin Wound Dressing for Accelerated Wound Healing

Tissue Eng Regen Med. 2025 Jun;22(4):515-526. doi: 10.1007/s13770-025-00712-1. Epub 2025 Feb 26.

Abstract

Background: Skin wound healing is a complex process requiring coordinated cellular and molecular interactions. Polynucleotides (PN) and hyaluronic acid (HA) have emerged as promising agents in regenerative medicine due to their ability to enhance cellular proliferation, angiogenesis, and extracellular matrix (ECM) remodeling. Combining PN and HA offers potential synergistic effects, accelerating wound repair.

Methods: PN and HA hydrogels were prepared and evaluated for viscosity and gel stability. Their effects on human dermal fibroblasts (HDF) and keratinocytes (HaCaT) were assessed using migration, proliferation assays, and gene expression analyses for vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-10 (MMP-10). In vivo studies were conducted using a mouse wound model to observe wound closure and tissue regeneration over 14 days.

Results: The PN-HA mixture demonstrated superior mechanical stability compared to individual components. In vitro, PN-HA significantly enhanced HDF and HaCaT migration, proliferation, and upregulated VEGF, MMP-9, and MMP-10 expression. In vivo, PN-HA treatment accelerated wound closure, improved dermal thickness, and enhanced ECM remodeling, as evidenced by histological analyses.

Conclusion: The PN-HA combination synergistically accelerates wound healing by promoting angiogenesis, cellular migration, and ECM remodeling. These findings highlight its potential as an advanced wound dressing for acute and chronic wound management.

Keywords: Hyaluronic acid; Polynucleotide; Wound dressing; Wound healing.

MeSH terms

  • Animals
  • Bandages*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Skin* / drug effects
  • Skin* / injuries
  • Skin* / pathology
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing* / drug effects

Substances

  • Hyaluronic Acid
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 9