Lignin-capped silver nanoparticles were incorporated in situ into polyurethane foams during their polymerization to obtain multifunctional materials suitable for chronic wound dressing. Lignin with increased phenolic content, achieved through the enzymatic grafting of natural phenolic compounds, played the dual role of a silver reducing agent in the synthesis of the lignin-capped silver nanoparticles and as a nanoformulated polyol additive in the polyurethane composition able to react with isocyanate. The nanoparticles-embedded polyurethane foams showed over 4 and 5 logs bacterial growth reduction against the Gram-positive S. aureus and the Gram-negative P. aeruginosa, respectively, attributed to both the direct contact- and release-killing mechanisms. The swelling properties of the foams, related to their capacity to remove the excess of wound exudates containing deleterious oxidative species and enzymes, varied from 585 to 1145% as a function of the content of nanoparticles. Overall, the physicomechanical and antibacterial properties of the foams, together with their biocompatibility and sustained release of silver, make these multifunctional materials suitable candidates for chronic wound dressings.
The healing of chronic wounds requires intensive medical intervention at huge healthcare costs. Dressing materials should consider the multifactorial nature of these wounds comprising deleterious proteolytic and oxidative enzymes and high bacterial load. In this work, multifunctional hydrogels for chronic wound application were produced by enzymatic cross-linking of thiolated chitosan and gallic acid. The hydrogels combine several beneficial to wound healing properties, controlling the matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) activities, oxidative stress, and bacterial contamination. In vitro studies revealed above 90% antioxidant activity, and MPO and collagenase inhibition by up to 98 and 23%, respectively. Ex vivo studies with venous leg ulcer exudates confirmed the inhibitory capacity of the dressings against MPO and MMPs. Additionally, the hydrogels reduced the population of the most frequently encountered in nonhealing wounds bacterial strains. The stable at physiological conditions and resistant to lysozyme degradation hydrogels showed high biocompatibility with human skin fibroblasts.
This work describes the enzymatic synthesis of multifunctional hydrogels for chronic wound treatment using thiolated chitosan and the natural polyphenol chicoric acid. Gelation was achieved by laccasecatalyzed oxidation of chicoric acid, a natural compound used for the first time as a homobifunctional crosslinker, reacting subsequently with nucleophilic thiol and amino groups from the chitosan derivative.This approach allowed for twice as fast gelation at a three-fold reduced crosslinking reagent concentration, compared to reported enzymatic synthesis of hydrogels using gallic acid as a phenolic provider. Hydrogels with 600% swelling capacity, coupled with only 20% weight loss after 6 days under physiological conditions, were obtained. The clinically relevant Gram-positive Staphylococcus aureus and the Gram-negative Pseudomonas aeruginosa were reduced by up to 4.5 and 5.5 logs, respectively. A tunable, in the range of 20-95%, ex vivo inhibition of myeloperoxidase (MPO) activity in chronic wound exudate was achieved, together with control over the total matrix metalloproteinase (MMP) activities.
Bleomycin (BLM) administration is associated with multifunctional proteins inflammations and induction of idiopathic pulmonary fibrosis (IPF). Lemna minor L. extract, a free-floating monocot macrophyte possesses antioxidant and anti-inflammatory potential. The aim of the study was to examine the protective effect of L. minor extract on lung protein oxidation and oxidative stress modulation by BLM-induced pulmonary fibrosis in Balb/c mice. For this purpose, the protein carbonyl content, advanced glycation end product, nitroxide protein oxidation (5-MSL), and lipid peroxidation (as MDA and ROS), in lung cells were examined. The histological examinations, collagen deposition, and quantitative measurements of IL-1β, IL-6, and TNF in lung tissues and blood were investigated. Intraperitoneal, BLM administration (0.069 U/mL; 0.29 U/kg b.w.) for 33 days, caused IPF induction in Balb/c mice. Pulmonary combining therapy was administered with L. minor at dose 120 mg/mL (0.187 mg/kg b.w.). L. minor histologically ameliorated BLM induced IPF in lung tissues. L. minor significantly modulated (p < 0.05) BLM-alterations induced in lung hydroxyproline, carbonylated proteins, 5-MSL-protein oxidation. Oxidative stress decreased levels in antioxidant enzymatic and non-enzymatic systems in the lung were significantly regulated (p < 0.05) by L. minor. L. minor decreased the IL-1β, IL-6, and TNF-α expression in lung tissues and plasma. The L. minor improves the preventive effect/defense response in specific pulmonary protein oxidation, lipid peroxidation, ROS identifications, and cytokine modulation by BLM-induced chronic inflammations, and could be a good antioxidant, anti-inflammatory, and anti-fibrotic alternative or IPF prevention involved in their pathogenesis.
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