## 5 Nanoformulations for Wound Healing
### Electrospun Nanofibers Loaded with Phytochemicals
In an interesting study, chlorogenic acid was loaded into dopamine (DA)-functionalized alginate (Alg-DA) conjugates and further impregnated into innovative wound dressings based on PVA. The nanofibrous mats displayed improved water absorption, a desirable water vapor transmission rate, and porous morphology, as well as a hydrophilic nature. Additionally, the biocompatible nanofibrous matrices showed antibacterial activities, improved antioxidant activity, and can effectively protect cells from oxidative damage. Finally, the multifunctional wound dressings showed the promotion of wound healing and could be a promising solution for wound healing and the management of wound infections [89]. Poly(\(\varepsilon\)-caprolactone)-PCL, a semi-crystalline synthetic polymer, is frequently utilized in tissue engineering applications owing to its biocompatibility and biodegradability, as well as desirable mechanical properties. The combination of PCL as a layer in bilayer wound dressings is well-studied. Therefore, PCL/PVA-CS nanofibrous dressings entrapping an ethanolic leaf extract of _Tridax procumbens_ L. were examined for their antibacterial and tissue regeneration effects. The biocompatible nanofibers (studied using the L929 cell line) exhibited a greater inhibition of _E. coli_ than _S. aureus_, as well as improved wound healing in biopsy punch wounds and laser burns [90]. An electrospun nanofibrous mat with a top layer of PCL-silk sericin and bottom layer of chitosan-alginate hydrogel was studied for its possible use in combating wound infections. The inner layer was loaded with 10-hydroxydecanoic acid (10-HDA), known as queen bee acid, an anti-inflammatory, antibacterial, and immunomodulatory agent. In vitro and in vivo studies revealed that the top layer exhibited a normal swelling index with protection against microbes, compared to the hydrogel-based layer, which demonstrated increased swelling and rapid healing. Interestingly, even 1% 10-HDA improved cell proliferation and antimicrobial activity. Finally, when the wound dressings were tested on Wistar rats, they enhanced wound healing without any inflammatory side effects, according to clinical and histological assessments combined with an analysis of their biophysical properties of skin healing [91]. Another nanofibrous wound dressing with multiple layers was developed, so as to mimic the skin structure; the top layer comprised a cellulose microfiber, while the bottom layer was made from pectin, soy protein isolate, and pomeranate peel extract. The bilayer nanofibrous mats exhibited notable mass loss in PBS solution and improved mechanical properties. The cytocompatible wound dressing demonstrated cell adhesion, angiogenesis, and rapid wound healing activity in vivo, being classified as a promising approach for clinical applications [92]. [PERSON] et al. fabricated multilayered nanofibrous matrices composed of PCL and collagen incorporating Malva sylvestris extract, and an inactive layer with only PCL. The diameters of the fibers ranged from 120 to 140 nm, while the water vapor transmission values of the NFs could be compared to those of commercial dressings such as Tegaderm, Bioclusive, and Op Site. Additionally, the electrospun nanomats showed improved water uptake, which can be beneficial for wound exudate handling, while prolonging the release of the extract. The biocompatible nanofibers demonstrated hemocompatibility and rapid blood clotting, along with improved tissue regeneration [93]. Curcumin, a polypheniotive compound that is widely found in many plant species, most commonly in Curcumin longa, and berberine, a derivative of the parent molecule berberine, both demonstrate strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Therefore, [PERSON] et al. examined the synergistic action of these phytochemicals when loaded into a PCL nanofibrous matrix. The nanofibers demonstrated an effective inhibitory potency against MRSA growth, along with improved mechanical properties, swelling ability, and thermal stability.