As the body's largest vital organ, skin is vulnerable to injuries that can compromise its integrity and cause skin wounds (Liao et al., 2015). Therefore, the skin must go through a wound healing process to regain its proper function. The process of normal skin wound healing represents a major challenge as it involves a complex physiological process that occurs through four overlapping phases; Proliferation, hemostasis, inflammation and remodeling (El Ayadi et al., 2020). The global burden of morbidity and mortality is significantly increased by impaired wound healing and its associated complications (Chigurupati et al., 2013). The wounds with pre-existing pathophysiological abnormalities such as diabetic ulcers show delayed adaptation and impaired wound healing progress (Liu et al., 2021).

Medical complications associated with diabetic ulcers, such as severe infections, persistent inflammation, and failure to close wounds, are a leading cause of death in diabetics. The prolonged inflammatory phase, leading to an increase in oxidative stress, is the main cause of difficulties associated with diabetic ulcers (Majd et al., 2016). However, due to the tremendous advances in our scientific understanding of the repair process, there are many optimistic reasons for treating such wounds. Dressings create favorable conditions at the injury site and serve as a supplement to the wound healing process (Lin et al., 2020). A favorable wound dressing would be tissue-compatible, gas-permeable, protect the wounds from infections, prevent dehydration, have effective exudate absorption, promote the restoration of epithelium and accelerate the healing process. Therefore, developing an efficient antimicrobial wound care method can greatly accelerate the wound healing process (Bakshi, 2017, Cao et al., 2021, Yu et al., 2016).

There are a variety of effective methods and resources for making wound coverings (Mirmohseni et al., 2020, Rivera-Briso et al., 2020). Among them, electrospinning occupies a leading position, due to its simplicity and reasonable flexibility. These advantages enable the use of a wide variety of biomaterials. These advantages facilitate the use of a wide variety of biomaterials. Nanofiber mats can be considered a valuable type of wound dressing because they have a structure similar to extracellular matrix (ECM). The porous nature of nanostructures absorbs wound exudates extremely efficiently and promotes the penetration of oxygen into the wound bed (Abrigo et al., 2014, James et al., 2016, Naseri-Nosar et al., 2017).

In the last two decades, new advances have been made in the field of developing innovative electrospinning-based wound dressings for wound healing by combining various synthetic or natural polymers and incorporating bioactive agents, nanoparticles and drugs through the electrospinning process (Mirbagheri et al., 2023, Sadeghi-Aghbash et al., 2023). Electrospinning of natural and synthetic biopolymers of different origins, natural and renewable sources, to produce dressings and scaffolds for tissue engineering is valuable to the current wound care industry due to their bioactivity, biodegradability, biocompatibility and other specific structures (Li et al., 2023). Nanofibers could also deliver bioactive agents to the wound site including antibacterial particles (Li et al., 2019), various nanoparticles (Yu et al., 2022), stem cells (Shalaby et al., 2015), antibiotics (Gandavadi et al., 2019), plant metabolites (Tian et al., 2007, Varshosaz et al., 2011), which can activate cell migration and proliferation as well as the differentiation of damaged cells.

In recent years, biodegradable polymers have been widely used as promising biomaterials to improve the regeneration and repair of injured tissues. (Hasan et al., 2018, Mhanna and Hasan, 2017). Many polymers have been successfully used to produce biomaterials for drug delivery. (Augustine et al., 2019), tissue engineering (Ghosal et al., 2017) and wound healing applications (Andrabi et al., 2020). Polycaprolactone is a widely recognized type of such polymers. The biodegradable and biocompatible properties of electrospun poly ƹ-caprolactone (PCL) nanofibers as well as their ability to mimic the extracellular matrix (ECM) in combination with bioactive substrates, make them an important component in tissue engineering (Naseri-Nosar et al., 2017).

Cellulose acetate is one of the various biocompatible polymers used to create electrospun scaffolds. This polymer offers useful advantages including affordability, renewability, and ease of mass production (Iravani and Varma, 2019, Novotna et al., 2013). Cellulose acetate is a highly recommended material for electrospinning due to its good solubility in organic solvents. In addition, it is non-toxic, biodegradable and biocompatible, has a high affinity for other substances, and has excellent mechanical and regenerative properties. These factors have led to the widespread use of cellulose acetate in studies related to skin tissue engineering and wound dressings. (Dos Santos et al., 2021).

Excessive production of free radicals leads to harmful cytotoxic effects, triggers oxidative stress and delays the wound healing process (Fahimirad and Ghorbanpour, 2019). Therefore, the use of an appropriate anti-inflammatory and antioxidant agent may be an important strategy to improve wound healing by reducing excess free radicals and persistent inflammation. (Rather et al., 2018, Sadidi et al., 2020).

Cerium oxide nanoparticles (CeO2 NPs) possess exceptional properties, including antibacterial, anti-inflammatory, antioxidant, angiogenic, and anti-apoptotic functions, making them one of the most promising biologically active agents. (Sadidi et al., 2020). CeO2 NPs have been shown to exhibit both enzyme mimetic activity and antioxidant properties in biological systems. (Augustine et al., 2019). In recent decades, it has been discovered that nanoparticles such as CeO2 NPs can act as free radical scavengers and effectively remove excess reactive oxygen and nitrogen species (ROS and RNS). The antioxidant properties of CeO2 NPs have attracted great interest in their potential biomedical applications. (Shcherbakov et al., 2021).

Cerium oxide nanoparticles have low solubility and settle quickly in organic solvents. Therefore, the mixing process in producing the nanoparticles could not distribute the nanoparticles evenly on the nanofibers. In order to exploit the antibacterial and wound healing effects of cerium oxide, it was also necessary to achieve a slow release of the nanoparticles into the wound base. In addition, chitosan, a natural antibacterial biopolymer, can enhance the biological effects of cerium oxide nanoparticles through synergistic action. Therefore, in this study, we prepared the cerium oxide nanoparticles using Thymus vulgaris extract with proven biological properties. The best conditions for a green synthesis of nanoparticles have been optimized. Subsequently, some biological and morphological properties of the prepared nanoparticles were evaluated. With the aim of improving the biological properties of the synthesized nanoparticles and enabling controlled release, the prepared CeO2NPs were encapsulated into chitosan nanoparticles. The encapsulated nanoparticles were then examined for their biological and morphological properties. Polycaprolactone and cellulose acetate were electrospun into a bilayer nanostructure to provide a wound dressing with favorable properties such as porosity, water absorption, and biodegradability. Finally, chitosan-cerium oxide encapsulated nanoparticles (CeO2-CSNPs) were electrosprayed onto the cellulose acetate-based layer of the nanoscaffold to improve the antimicrobial properties through the controlled release of the green synthesized CeO2NPs in the wound area. The benefits of this nanostructure in diabetic wound repair were investigated through the analysis of in vitro and in vivo studies. In this experiment, polycaprolactone/cellulose acetate nanofibers were electrosprayed with green synthesized cerium oxide nanoparticles encapsulated in chitosan for the first time. The research significance would be underlined by a good wound healing performance of the produced nanostructure.