Tissue engineering (TE) holds an enormous potential to develop functional scaffolds resembling the structural organization of native tissues, to improve or replace biological functions and prevent organ transplantation. Amongst the many scaffolding techniques, electrospinning has gained widespread interest because of its outstanding features that enable the production of non-woven fibrous structures with a dimensional organization similar to the extracellular matrix. Various polymers can be electrospun in the form of three-dimensional scaffolds. However, very few are successfully processed using environmentally friendly solvents; poly(vinyl alcohol) (PVA) is one of those. PVA has been investigated for TE scaffolding production due to its excellent biocompatibility, biodegradability, chemo-thermal stability, mechanical performance and, most importantly, because of its ability to be dissolved in aqueous solutions. Here, a complete overview of the applications and recent advances in PVA-based electrospun nanofibrous scaffolds fabrication is provided. The most important achievements in bone, cartilage, skin, vascular, neural and corneal biomedicine, using PVA as a base substrate, are highlighted. Additionally, general concepts concerning the electrospinning technique, the stability of PVA when processed, and crosslinking alternatives to glutaraldehyde are as well reviewed.
Wound healing requires careful, directed, and effective therapies to prevent infections and accelerate tissue regeneration. In light of these demands, active biomolecules with antibacterial properties and/or healing capacities have been functionalized onto nanostructured polymeric dressings and their synergistic effect examined. In this work, various antibiotics, nanoparticles, and natural extract-derived products that were used in association with electrospun nanocomposites containing cellulose, cellulose acetate and different types of nanocellulose (cellulose nanocrystals, cellulose nanofibrils, and bacterial cellulose) have been reviewed. Renewable, natural-origin compounds are gaining more relevance each day as potential alternatives to synthetic materials, since the former undesirable footprints in biomedicine, the environment, and the ecosystems are reaching concerning levels. Therefore, cellulose and its derivatives have been the object of numerous biomedical studies, in which their biocompatibility, biodegradability, and, most importantly, sustainability and abundance, have been determinant. A complete overview of the recently produced cellulose-containing nanofibrous meshes for wound healing applications was provided. Moreover, the current challenges that are faced by cellulose acetate- and nanocellulose-containing wound dressing formulations, processed by electrospinning, were also enumerated.
New approaches to deal with the growing concern associated with antibiotic-resistant bacteria are emerging daily. Essential oils (EOs) are natural antimicrobial substances with great potential to mitigate this situation. However, their volatile nature, in their liquid-free form, has restricted their generalized application in biomedicine. Here, we propose the use of cellulose acetate (CA)/polycaprolactone (PCL) wet-spun fibers as potential delivery platforms of selected EOs to fight infections caused by Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Twenty EOs were selected and screened for their minimal inhibitory concentration (MIC), using the antibiotic ampicillin as positive control. The cinnamon leaf oil (CLO), cajeput oil (CJO), and the clove oil (CO) were the most effective EOs, against the Gram-positive (MIC < 22.38 mg/mL) and the Gram-negative (MIC < 11.19 mg/mL) bacteria. Uniform microfibers were successfully wet-spun from CA/PCL with an averaged diameter of 53.9 ± 4.5 µm, and then modified by immersion with CLO, CJO and CO at 2 × MIC value. EOs incorporation was confirmed by UV-visible spectroscopy, Fourier-transformed infrared spectroscopy, and thermal gravimetric analysis. However, while microfibers contained ampicillin at MIC (control) after the 72 h modification, the CLO, CO and CJO-loaded fibers registered ≈ 14%, 66%, and 76% of their MIC value, respectively. Data showed that even at small amounts the EO-modified microfibers were effective against the tested bacteria, both by killing bacteria more quickly or by disrupting more easily their cytoplasmic membrane than ampicillin. Considering the amount immobilized, CLO-modified fibers were deemed the most effective from the EOs group. These results indicate that CA/PCL microfibers loaded with EOs can be easily produced with increased antibacterial action, envisioning their use as scaffolding materials for the treatment of infections.
Poly(vinyl alcohol)/cellulose acetate (PVA/CA) films were prepared via a new method that combines principles from solvent casting and phase inversion. To guarantee some degree of flexibility, films were produced with a higher percentage of PVA compared to CA, from 90/10 to 50/50. The antimicrobial peptide (AMP) LL37 was then anchored using dopamine as a binding agent. Films were characterized in terms of functional groups, thermal stability, tensile strength, porosity, swelling, and degradation (stability in physiological media at different pHs). The antimicrobial performance of LL37 surface-modified films was tested against Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli in dynamic environment and in the presence and absence of an albumin interface. LL37 treated films demonstrated great antibacterial efficacy against the three kinds of bacteria, ≈75% inhibition for S. aureus, ≈85% for S. epidermidis, and ≈60% for E. coli, regardless of PVA/CA ratio. Presence of albumin reduced bacteria inhibition in all tested groups, most likely due to the binding of the protein molecules to the antimicrobial agents, reducing the free fraction available for bacterial killing. Films treated with LL37 accelerated clotting time (≈10 min) above vancomycin and bare surfaces, demonstrating great capacity to activate the intrinsic coagulation cascade.
Quercus suber cork generates bioactive components, such as phenolic acids, terpenoids, and tannins, with excellent biological properties, including antioxidant, anti-inflammatory, and antiaging activities. Aiming to design environmentally benign processes to eliminate, or reduce, the use of toxic chemicals, we propose the green extraction of bioactives from cork using natural deep eutectic solvents (NADES). Several deep eutectic mixtures were developed, through the mixture of natural compounds, namely, lactic acid, glycerol, ethylene glycol, sodium citrate, and sodium lactate, chosen according to their origin, toxicity, biocompatibility, polarity, and pH. The results revealed higher extraction yields when using NADES instead of harsh solvents like dioxane, with the extraction process governed by several physical–chemical parameters, including pH, polarity, viscosity, and density, and also by the method of extraction. Acidic NADES composed of lactic acid and glycerol, or sodium citrate, extracted a greater amount of aromatic compounds, terpenoids, and fatty acids and their derivatives. More basic eutectic mixtures, composed of sodium lactate and a polyol (ethylene glycol or glycerol), extracted predominantly low molecular weight polar compounds. The extracts range encompassed by the developed NADES, together with the associated nontoxicity, low price, and ease of preparation, establish these solvents as a green approach to extract high added-value compounds from cork.
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