As the body's primary shield, the skin plays a crucial protective role against various infections and mechanical, thermal, and microbial damage [1]. When this layer is injured or wounded, the skin loses its protective function [2]. The wound healing process involves a complex series of biological events, including hemostasis, inflammation, proliferation, and tissue remodeling. During these stages, various cells such as fibroblasts and keratinocytes coordinate to repair tissue damage and restore skin integrity [[3], [4], [5]]. Additionally, wound infections remain a common and unresolved challenge in wound healing, as any skin wound is susceptible to the accumulation of infectious bacteria, which can hinder the healing process [6]. Conventional dressings, such as gauze, lack antibacterial properties and may adhere to newly repaired tissue, causing pain upon removal [7]. Therefore, an advanced wound dressing should possess antibacterial and antioxidant properties, maintain moisture, facilitate faster wound tissue regeneration, and manage excess wound secretions [8]. It should also be non-toxic, non-adhesive, biocompatible, and capable of accelerating cell healing and regeneration [9]. Consequently, there is a significant need for biocompatible and biodegradable wound dressings based on bioactive compounds that can promote wound healing and the regeneration of damaged skin [10].

Nanofibers are considered ideal wound dressing materials due to their high surface area, biocompatibility, and water absorption capacity [11,12]. Their porous structure enhances the loading of pharmaceuticals and various biological molecules, enabling continuous delivery of these compounds to the surrounding environment [13]. Additionally, their high porosity makes them suitable for ventilation and air exchange in the wound healing area [14]. Nanofibers can be produced using techniques such as electrospinning, melt-blowing, spin-blowing, pattern-based synthesis, centrifugal spinning, and microfluidic spinning [15].

Electrospinning is one of the most widely used and efficient techniques for fabricating nanofibers from polymer solutions or composites due to its simplicity, low cost, and ability to produce fibers with nanoscale diameters. While traditional single-fluid blending electrospinning has enabled the encapsulation of active compounds within a homogeneous polymeric matrix, recent advances have led to the development of more complex configurations, including coaxial (bi-fluid) electrospinning [16,17], side-by-side electrospinning [18], and triaxial or multilayered systems [19,20], which allow for more precise control over drug release profiles and fiber architecture. Despite these innovations, the single-fluid blending method remains highly practical and advantageous for biomedical applications due to its scalability, reproducibility, and capacity to incorporate multiple bioactive agents in a cost-effective manner [21,22]. Therefore, in this study, we employed the single-fluid electrospinning technique as a rational and efficient strategy for the development of multifunctional wound dressing nanofibers.

PVP is one of the most widely used synthetic polymers in pharmaceutical and biomedical applications due to its excellent biocompatibility, hydrophilicity, and film-forming ability. In drug delivery systems, PVP plays a dual role: it is not only employed to enhance the solubility and rapid dissolution of poorly water-soluble drugs, but it is also utilized as a versatile matrix-forming agent in the design of controlled drug release profiles. Recent studies have demonstrated that incorporating PVP into composite systems enables the modulation of drug release kinetics through various advanced strategies, including solid dispersions, nanofiber encapsulation, and multi-component formulations [[23], [24]]. Furthermore, its compatibility with a wide range of active pharmaceutical ingredients and excipients makes it an ideal candidate for the development of multifunctional drug delivery platforms. In this study, PVP was selected as the base polymer for electrospinning due to these advantageous properties, particularly in combination with natural biopolymers such as neem gum.

As mentioned above, electrospun PVP nanofibers are highly effective for drug incorporation and release [25]. However, these nanofibers exhibit significant dissolution in humid environments due to their exceptionally high surface-to-volume ratio [26]. It is worth noting that no single material can fully meet all the requirements of the wound healing process [27]. To address these limitations, PVP can be electrospun with polysaccharides, other polymers, and pharmaceutical compounds to produce composite nanofibers with adjustable properties [28,29].

Neem gum (NG) polysaccharide, obtained from Azadirachta indica, is a biocompatible and hydrophilic polymer [30,31]. Composed of arabinose, glucosamine, xylose, galactose, and glucose, neem gum is a natural plant secretion resulting from damage [32]. This anionic linear polysaccharide has gained attention for its medicinal properties in treating various skin diseases, infections, and inflammations [33]. Its advantages include natural origin, availability, biocompatibility, antibacterial activity, and an abundance of functional groups [34]. The presence of numerous functional groups, such as hydroxyl, carboxylic, and ketone groups, creates an ideal environment for interactions with other polymers [35]. Recently, incorporating bioactive compounds into polymeric nanofiber dressings has emerged as a promising approach for wound management [36,37]. Composite nanofibers made from neem gum combined with PVP exhibit significant intrinsic wound healing potential and promote the regeneration of damaged tissue.

The healing properties of clove essential oil (CEO) have been recognized since ancient times and have been utilized in various applications [38]. This compound exhibits antioxidant, antibacterial, anti-inflammatory, and anticancer activities, along with significant wound healing potential [39]. The antioxidant activity of CEO is attributed to the presence of high levels of eugenol, caryophyllene, and phenylpropanoids [40]. Additionally, CEO demonstrates strong antibacterial activity against various pathogens, including Staphylococcus aureus, Bacillus cereus, Salmonella typhimurium, Escherichia coli, and Aspergillus [41]. It is also an effective scavenger of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical [42]. Despite these advantages, CEO is a hydrophobic compound and is highly sensitive to light and temperature, making its direct incorporation into hydrophilic nanofiber networks for wound dressings challenging [43,44].

β-Cyclodextrins (β-CD) are often used as selective carriers for hydrophobic substances due to their amphiphilic nature, featuring a hydrophobic interior and a hydrophilic exterior, as well as the orientation of glycosidic bonds within the carrier cavity [45,46]. β-CD can form complexes with hydrophobic CEO in its interior through hydrogen bonding and van der Waals interactions [47]. Meanwhile, the hydrophilic outer surface of β-CD disperses well in PVP/NG polymer solutions and can be easily electrospun [48]. In this way, CEO encapsulated in β-CD can be integrated into nanofiber structures, facilitating the development of an ideal wound dressing.

The aim of this study is to design an ideal wound dressing using electrospun PVP/NG nanofibers containing varying percentages of CC (CEO-loaded β-CD), with antibacterial, anti-inflammatory, and antioxidant properties. The surface morphology, thermal stability, degradability, mechanical properties, swelling behavior, antioxidant activity, cell viability, antibacterial activity, hemolysis, and biodegradability of the electrospun bionanocomposite scaffolds were investigated under laboratory conditions. In continue, we explicitly emphasized the key innovative aspects of our study: (a) Enhanced Drug-Loading Efficiency: The encapsulation of CEO into β-CD inclusion complexes not only improves the stability and solubility of the oil but also ensures controlled and sustained release, resulting in higher effective bioavailability compared to direct loading. (b) Improved Biocompatibility: The use of natural polymers such as PVP and NG offers excellent biocompatibility, as confirmed by hemolysis, cytotoxicity, and cell proliferation assays. The composite scaffold showed no hemotoxic effects and supported cell attachment and growth, validating its suitability for wound healing. (c) Scalable and Simple Fabrication: Our single-fluid electrospinning approach is a cost-effective and scalable method for producing uniform nanofibers, making the system feasible for large-scale production and clinical translation. The preparation of PVP/NG/CC electrospun nanofibers is schematically illustrated in Scheme 1.