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.

Doxycycline release and antibacterial activity from PMMA/PEO electrospun fiber mats

“…The hypothesis is that the release of significant PEO amounts from PMMA might open up the matrix slightly, so that water can access deeper fiber areas to solubilize and release doxycycline. Blended fibers using hydrophobic and hydrophilic polymers as PMMA and PEO may produce a prolonged and controlled release system for other drugs 21 , 22 . The large surface area, associated with spun fabrics, allows fast and efficient solvent evaporation, providing incorporated drug limited time to recrystallize, which favors the formation of amorphous dispersions or solid solutions of drug in polymer 23 …”

Kynurenic Acid Accelerates Healing of Corneal Epithelium In Vitro and In Vivo

“…The antiscarring properties of topically applied KYNA in a skin wound-healing model in rabbits and rats were reported [ 25 , 45 ]. Importantly, KYNA enhanced the expression of matrix metalloproteinases MMP1 and MMP3 and suppressed the production of type I collagen and fibronectin by fibroblasts [ 25 ].…”

Nanofibrous Scaffolds for Skin Tissue Engineering and Wound Healing Based on Synthetic Polymers

“…Poly(methyl methacrylate) (PMMA) nanofibers were used for construction of antiscarring wound dressings. PMMA containing polyethylene glycol and kynurenic acid, an antifibrotic agent, suppressed proliferation of fibroblasts in vitro, and when administered as wound dressing in rats in vivo, they inhibited expression of collagen and fibronectin, and enhanced the production of matrix metalloprotease 1 (MMP-1), an ECM-degrading enzyme [48]. In addition, core-shell nanofibers containing PVA and PMMA were used for delivery of ciprofloxacin hydrochloride, an antibiotic [49].…”

“…PVA was used as emulsifier in fabrication of blended electrospun PLGA/chitosan nanofibers for potential skin reconstruction [113]. PVA and particularly PVP are important components of nanofibers delivering various biomolecules and drugs into skin, such as antibiotics (PVA [49], PVP [114]), kynurenine (PVA [48]), curcumin and HHC36 antimicrobial peptides (PVP [8]) or antimicrobial suberin fatty acids isolated from outer birch bark (PVP [115]). PVA and PVP were combined in electrospun nanofibrous membranes designed for sustained release of the antibiotic ciprofloxacin into wounds [116].…”