## 4 Essential Oils as Active Secondary Compounds in Wound Dressings

Table 1: \(Cont.\)collagen nanofibers and evaluated the dressing system in an antimicrobial test [149]. The microbiological results showed that the nanofibers were active against _S. aureus_, _E. coli_, _P. aeruginosa_, and _C. albicans_[149]. Cinnamaldehyde (CAL) or (2E)-3-Phenylprop-2-enal is found in cinnamon essential oil (55-76%) isolated from cinnamon trees, camphor, and cassia. CAL is used in wound healing for antibacterial and antifungal activity and as an anti-inflammatory agent (Figure 3) [150]. [PERSON] et al. incorporated CAL into gelatin/chitosan biopolymer membranes and investigated their microbiological activity [151]. The result showed that the developed CAL/gelatin/chitosan membranes inhibited the growth of three Gram-negative bacteria species (_P. aeruginosa_, _Salmonella_, and _E. coli_) and one Gram-positive bacteria species (_S. aureus_). Based on their results, they proposed that the bioactive, biodegradable, and nontoxic CAL/gelatin/chitosan membranes could be a promising candidate for wound dressing applications [151]. In another study, [PERSON] et al. demonstrated the antimicrobial activity of cinnamon, lemongrass, and peppermint essential oils encapsulated in cellulose-based fiber dressings. These formulated products inhibited the growth of Escherichia coli and showed good biocompatibility when tested on fibroblasts and keratinocytes as cell models (NIH3T3 and HaCaT cells) [152]. Another essential oil widely used in wound healing is tea tree oil (TTO), which is extracted from the leaves of _M. alternifolia_[153, 154]. Three main compounds of TTO, terpinen-4-ol, \(\gamma\)-terpinene, and \(\alpha\)-terpinene are shown in Figure 3[155]. The presence of terpene hydrocarbons and tertiary alcohols results in TTO antimicrobial and anti-inflammatory activity and helps in the regeneration of collagen [156]. In one study, [PERSON] et al. formulated a TTO nanocapsule (TTO-NC) and nanoemulsions (TTO-NE) into the hydrogels separately and compared both systems [102]. They investigated their influence on the treatment of inflammatory disorders and wound healing [102]. The result showed that both formulated hydrogels could promote the healing process, although the TTO-NC hydrogel could heal the wounds faster than TTO-NE by reducing inflammation [102]. Green tea extract (GT) is another tea tree product isolated from the leaf of _Camelia sinensis_. [PERSON] et al. formulated green tea extract in chitosan/polyethylene oxide nanofiber to investigate the wound-healing effect of GT [157]. The antibacterial assay on chitosan/PEO/GT nanofibers showed inhibition against _Escherichia coli_ and _Staphylococcus aureus_. The in vivo study was  
Figure 3: (**a**) Cinnamaldehyde, (**b**) and (**c**) two main oregano oil ingredients thymol and carvacrol, (**d**), (**e**) and (**f**) three main tea tree oil compounds \(\alpha\)-terpinene, \(\gamma\)-terpinene, and terpinen-4-ol, and (**g**) 1,8-cineole one of the main ingredient of eucalyptus oil. conducted on rat, and the result showed that chitosan/PEO/GT nanofiber could accelerate the healing process, and the wound recovered completely after 16 days [157]. Eucalyptus oil with its main compound 1,8-cineole is extracted from Eucalyptus globulus, an evergreen tree with endemic wild growth in southeastern Australia (Figure 3) [158]. [PERSON] et al. formulated a eucalyptus oil nanoemulsion for topical application to investigate the antibacterial and wound-healing potential against _Staphylococcus aureus_ and Wistar rats, respectively [158]. The O/W nanoemulsions were prepared by ultrasonic method using the nonionic surfactant Tween 80. They showed that the viability of _Staphylococcus aureus_ was affected within 15 min of contact with the eucalyptus oil nanoemulsion, and bacterial membrane damage occurred. Animal studies showed a higher wound contraction rate compared to control and neomycin and confirmed that the formulation was not irritating [158]. In another study, [PERSON] et al.