title: Development of a nanofibrous wound dressing with an antifibrogenic properties in vitro and in vivo model.
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.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Malihe-Sadat
authors.initials: MS
authors.lastname: Poormasjedi-Meibod
authors.affiliation: Division of Plastic Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Pakyari
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: John K
authors.initials: JK
authors.lastname: Jackson
authors.affiliation: Division of Plastic Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sanam
authors.initials: S
authors.lastname: Salimi Elizei
authors.affiliation: Division of Plastic Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
mesh_terms: D000818:Animals; D001458:Bandages; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007736:Kynurenic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D057139:Nanofibers / Q000737:chemistry*; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D020318:Rats, Long-Evans
chemical_list: D019904:Polymethyl Methacrylate; D007736:Kynurenic Acid
keywords: electrospinning; extracellular matrix; kynurenic acid; skin fibrosis; wound dressing