## 5 Nanoformulations for Wound Healing
### Electrospun Nanofibers Loaded with Phytochemicals
The biocompatible mats, when studied in vivo in zebrafish models, exhibited rapid wound closure [94]. Oryzanol is a mixture of lipids originating from rice (_Oryza sativa_) and has numerous uses in the food and biomedical industries. The main problem of oryzae0 comes with its low aqueous solubility and its photothermal stability. Cyclodextrin complexation is a known procedure to enhance the solubility of poorly soluble agents; in a recent study, oryzanol was encapsulated into modified \(\beta\)-cyclodextrinrin and further loaded into PCL-CS nanofibrous matrices. According to the results, cyclodextrin complexes of oryzanol demonstrated improved antibacterial and wettability properties, while the matrices showed tissue re-epithelialization and reduced inflammation [95]. Another study employed wound-healing nanofibrous dressings based on PCL and cellulose acetate (CA) as matrices to inhibit microbial growth and improve wound healing. The mats were further loaded with _prinoides_ leaf, which is rich in many phytochemicals. It was revealed that the nanofiber-based mats, with a smooth morphology and fiber diameters of 330-380 nm, had antibacterial potential against _S. aureus_ and _E. coli_. Furthermore, the PCL-CA mats improved cell migration to the wound area, while _Rhamnus prinoides_ enhanced their hydrophilic nature and aqueous absorption [96]. Electrospun nanonets/mats based on PCL and collagen, fabricated with acetic acid and formic acid and loaded with propolisis extract, were studied for their wound healing potential. Propolis extract is widely used due to its wound healing capability. The nanoscaffolds with fibers displayed diameters ranging from 164 to 728 nm, while the nanonets were around 20 nm. From the results, the water vapor transmission rate values of the nanofibers/nanonets were similar to commercial dressings such as Tegaderm. Additionally, the propolis-loaded NFNs showed strong cytoprotective effects, while the viability of HFF-2 cells rose considerably after 72 h. Furthermore, the nanonats' hemocompatibility underscores their potential as treatments for wound healing [97]. Dihydromyricetin is a natural flavonoid derived from traditional Chinese medicines, i.e., _Hovenia dulcis_ and _Ampelopsis grossedentata_, and has shown wound healing promotion due to its antioxidant, antimicrobial, and anti-inflammatory properties. Nonetheless, this flavonoid is hydrophobic and prone to degradation by limiting its use. Inclusion complexes of dihydromyricetin and hydroxypropyl-\(\beta\)-cyclodextrinrin were developed and further incorporated into electrospun mats based on a blend of pectin polysaccharides (PPs), CS, and PVA. The fibers presented diameters ranging from 200 to 400 nm, comprising an interconnected matrix similar to that of the skin. In addition, the bio- and hemocompatible nanofibrous mats demonstrated an improved hydrophilicity and wettability, while flavonoids were sustainably released from the mat. Finally, the mats loaded with the inclusion complexes exhibited great antioxidant activity and halted the growth of _S. aureus_ and _E. coli_. In vitro and in vivo studies showed an enhanced wound healing process [98]. [PERSON] et al. developed a wound dressing with two layers to improve the multifunctionality of the dressings; the inner, which was crosslinked with genipin and CaCl\({}_{2}\), was based on SA and gelatin hydrogel, containing _Matricaria chamomilla_ L. extract and silver sulfadiazine as antibacterial agents, while the top surface layer was covered by electrospun polyacrylamide nanofibers. The mechanical and swelling properties of the dressings were improved, while the biodegradability, biocompatibility, and efficient antibacterial activity were also enhanced. Sustained release of the AgSD drug was found, while in vivo studies showed promoted wound healing [99].