Development of a nanofibrous wound dressing with an antifibrogenic properties in vitro and in vivo model

J Biomed Mater Res A. 2016 Sep;104(9):2334-44. doi: 10.1002/jbm.a.35770. Epub 2016 May 18.

Abstract

Dermal fibrosis, characterized by excessive extracellular matrix (ECM), is a pathological condition with limited effective therapeutic modalities. Lack of an antiscarring dressing further impedes the preventive measures for this condition. Here, we develop a new antiscarring dressing and investigate its potential as a slow-releasing vehicle for kynurenic acid (KynA), an antifibrotic agent. KynA was incorporated into polymethyl methacrylate (PMMA) nanofibers, containing increasing concentration of polyethylene glycol (PEG). Fibre morphology, water absorption capacity, surface hydrophilicity, in vitro drug release profile, and in vivo antifibrotic effects were investigated. Increasing concentrations of PEG (1-20%) significantly increased surface hydrophilicity, water absorption capacity, and drug release. Based on the obtained release profiles, PMMA + 10% PEG was the preferred formulation for sustained KynA release up to 120 hours. In vitro studies confirmed the preservation of KynA antifibrotic properties during electrospinning, indicated by fibroblasts proliferation suppression and ECM expression modulation. In vivo application of KynA-incorporated films significantly inhibited collagen (23.89 ± 4.79 vs. 6.99 ± 0.41, collagen-I/β-actin mRNA expression, control vs. treated) and fibronectin expression (7.18 ± 1.09 vs. 2.31 ± 0.05, fibronectin/β-actin mRNA expression, control vs. treated) and enhanced the production of an ECM-degrading enzyme (2.03 ± 0.88 vs. 11.88 ± 1.16 MMP-1/β-actin mRNA expression, control vs. treated). The fabricated KynA-incorporated films can be exploited as antifibrotic wound dressings. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2334-2344, 2016.

Keywords: electrospinning; extracellular matrix; kynurenic acid; skin fibrosis; wound dressing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bandages*
  • Fibroblasts / metabolism*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Kynurenic Acid* / chemistry
  • Kynurenic Acid* / pharmacokinetics
  • Kynurenic Acid* / pharmacology
  • Male
  • Nanofibers / chemistry*
  • Polymethyl Methacrylate / chemistry*
  • Rats, Long-Evans

Substances

  • Polymethyl Methacrylate
  • Kynurenic Acid