## 5 Nanoformulations for Wound Healing
### Electrospun Nanofibers Loaded with Phytochemicals  
Antibacterial wound dressings can be developed through various techniques such as phase separation [34], solvent casting [75], and electrospinning [76]. The electrospinning process is a widely used and versatile technique, which can produce fibrous and nanofibrous dressings [77] with a high surface to volume ratio and tunable mechanical properties. Their fibrous nature resembles the extracellular matrix enhancing cellular adhesion, proliferation, and differentiation, and, therefore, nanofibrous wound dressings have been extensively examined [78]. During the electrospinning process, a polymeric solution using biocompatible and/or biodegradable natural (i.e., chitosan (CS), hyaluronic acid (HA), alginic acid (AA), and gelatin (Gel)) or synthetic macromolecules (poly(lactic acid)-PLA, poly(lactic-co-glycolic acid)-plga, pol(vinyl pyrrolidone (PVP), and poly(vinyl alcohol-PVA)), is injected through a syringe equipped with a needle. The droplet that forms at the tip of the needle obtains a cone shape due to the applied voltage--known as a Taylor cone. When the Taylor cone is obtained, the fibers are collected on the metallic collector (drum or plate), creating a randomly or aligned oriented nanofibrous matrix (Figure 4). Throughout the literature, various wound dressings based on electrospun nanofibers have been identified, revealing interesting results with the potential to be clinically translated. Nanofibers are reportedly superior to various dressings such as cotton, gauze, sponge, hydrocolloids, and hydrogels [79]. They have a three-dimensional structure, increased porosity, surface with improved gas exchange, water vapor permeability, and enhanced active molecule delivery Electrospun wound dressings can incorporate antimicrobials, synthetic drugs, and growth factors to improve wound healing and minimize wound infections [28; 29]. However, in recent years, the incorporation of phytochemicals, natural substances, and extracts from plants into nanofibrous dressings has been shown to improve tissue regeneration, modulate inflammation, and increase cost-effectiveness [20]. PVA is a semi-crystalline synthetic polymer. Due to its biodegradability, its major applications are in drug delivery, wound dressings, and as a scaffold for tissue regeneration. PVA-based wound dressing materials have increasingly attracted attention because of their many properties, including affordability, non-toxicity, biodegradability, and biocompatibility. An antibacterial scaffold based on PVA nanofibers loaded with flaxseed ethanolic extract was developed via electrospinning. Various ratios of flaxseed and PVA were studied, and the most optimal ratio was the 30% extract. Flaxseed, commonly known as _Linum usitatissimumum_, has been used to improve digestion, but has also shown other remarkable health effects. Herein, the authors concluded that the flaxseed extract PVA dressing inhibited the growth of _Salmonella_ Typhimuriumium, _Escherichia coli_, _Staphylococcus aureus_, and _Pseudomonas aeruginosa_ while improving wound healing [14]. [PERSON] et al. developed electrospun wound dressings based on PLA, PVA, and chitosan (CS) entrapping Hypericum perforatum L. The technique used herein was emulsion electrospinning. The fibrous matrices (Figure 5) exhibited promising properties for wound dressings because of their porous morphology, which was similar to the extracellular skin matrix and its swelling index, wettability, and water vapor transmission rate. Finally, the cytocompatible wound dressings displayed the inhibition of _S. aureus_ growth, which is an important parameter for wound healing [76]. In the last decade, chitosan, a natural biopolymer originating from the deacetylation of chitin and obtained from fungi, crustaceans shells, and insects, has been explored as a  
Figure 4: A standard electrospinning system; the device is comprised of a syringe pump, a syringe connected with a steel nozzle and filled with polymer solution, a high-voltage power source, and the collector.