Human skin keeps the internal fluid homeostasis and provides a barrier against damages caused by environmental factors (e.g. chemical, mechanical, radiological, etc.) [1], [2], [3], [4]. Thus, wound healing is a critical issue for the recovery of the skin integrity and any injury of the skin (could be resulted from a cut, burn, surgical operation, diabetes, vascular diseases, etc.) should be considered as a serious health problem [1], [5]. Currently, there is increasing attention on nano-sized materials (nanoparticles, nanofibers, nanotubes, etc.) for the management of skin wounds, due to their high surface-to-volume ratio, active ingredient loading ratio, permeability, and bioactivity [3], [5], [6]. Among these nano-sized materials, nanofibrous natural and/or synthetic polymers are recently being investigated as new alternative wound dressings thanks to their outstanding properties such as; large surface area, high porosity, biocompatibility, and resemblance to the human extracellular matrix (ECM) [4], [7], [8], [9], [10], [11], [12], [13], [14], [15]. Polymeric nanofibers with diameters ranging between nanometers to submicrons are produced under high applied voltage by a simple, versatile, and efficient method known as the electrospinning process [8], [9], [10], [13], [16], [17].

In biomedical applications, polymers derived from natural sources (e.g. gelatin, chitosan, collagen, silk sericin, etc.) are generally preferred due to their abundance, non-toxicity, biodegradability, and biochemical similarity with human extracellular matrix (ECM) components. As a result of these features, natural polymers can be easily accepted by the body without host immune responses and toxic effects [18], [19], [20], [21], [22], [23], [24], [25]. However, these biomaterials have some drawbacks which limit their applications in the biomedical field. For example, their mechanical properties are poor, material properties and degradation patterns may differ depending on the source, and there is a risk of microbial contamination and uncontrolled water uptake. On the other hand, synthetic polymers (e.g. poly(lactic acid), poly(ε-caprolactone), poly(ethylene oxide), poly(vinyl alcohol), etc.) are suggested to overcome these problems with their well-defined mechanical and degradation properties [4], [18], [19], [24]. But, these polymers lack cell recognition sites, may cause inflammatory response during degradation, and are highly hydrophobic which may hinder the penetration of aqueous cell suspensions through the polymer matrix [19], [26], [27].

In the present study, it is proposed to produce a nanofibrous wound dressing with a synergetic effect by preparing the blends of natural and synthetic polymers to overcome the drawbacks of both types of polymers and achieve unique systems with advanced physiochemical properties [28], [29], [30], [31], [32], [33], [34]. Poly(ω-pentadecalactone-co-δ-valerolactone) is a synthetic, hydrophobic, semi-crystalline, and biocompatible copolymer which was previously synthesized by the same method applied for the synthesis of poly(ω-pentadecalactone-co-ε-caprolactone) copolymer [35]. Briefly, copolymerization was carried out in toluene by the catalysis of lipase immobilized onto rice husk ashes which was also produced in previous studies [36]. Compared to ε-caprolactone (ε-CL), polymerization and/or copolymerization of δ-valerolactone (δ-VL) and its application in the biomedical field have attracted less attention, although the resulting polymers have similar physicochemical and biomedical properties with poly(ε-caprolactone) and its copolymers [37]. Besides, the copolymer of ω-pentadecalactone (ω-PDL) and δ-valerolactone (δ-VL) monomers is a newly synthesized polymer and there exist limited studies focusing on either its enzymatic/chemical synthesis or implementation in a biomedical application. Overall, participation of a copolymer of δ-VL in the nanofibrous blend would improve the literature impact of this article since it suggests an application of an alternative monomer to widely used ε-CL.

Electrospinning of enzymatically synthesized polymers is a challenging process because of their relatively low molecular weights which makes it difficult to collect fibers properly. However, enzymatically synthesized polymers do not contain any toxic residual metallic catalyst which improves the biocompatibility of the polymer and makes it preferable for biomedical applications [38], [39], [40], [41]. Thus, the application of an enzymatically synthesized copolymer as a wound dressing may improve the significance of the study. Enzymatically synthesized poly(ω-pentadecalactone-co-δ-valerolactone) copolymer, which has been involved in a nanofibrous structure for the first time, was expected to provide well-defined degradation and mechanical properties to the nanofibrous wound dressing and to avoid uncontrolled water uptake as a result of its hydrophobicity [18], [26]. Gelatin is a water-soluble, non-toxic, non-carcinogenic, non-immunogenic, biocompatible, and biodegradable natural polymer that is derived from the hydrolytic degradation of porcine or bovine collagen and is widely preferred for biomedical applications, such as wound healing and drug delivery [4], [20], [42], [43], [44], [45], [46], [47]. Gelatin is known to be easily accepted by the body without immunogenicity, to promote cell proliferation, and to provide site-specific drug transportation due to its functional groups [8], [20], [42], [44], [45], [47].

When fabricating a wound dressing, generally, an active ingredient (antibiotics, analgesics, anti-inflammatory drugs, growth factors, herbal contents, etc.) with antibacterial, anti-inflammatory, and/or antioxidant properties is incorporated within the nanofibrous polymer matrix [48], [49], [50], [51], [52]. By this way, it is expected to induce wound healing and enhance cell proliferation by the controlled release of this active ingredient [3], [53], [54], [55]. Curcumin is a prominent polyphenol component of turmeric obtained from the medicinal plant Curcuma longa. As a result of its anti-inflammatory, antioxidant, antibacterial, and anticancer features, curcumin is an important candidate to be applied in the medical field [56], [57], [58], [59]. Curcumin is widely preferred for the treatment of skin wounds since it can suppress wound inflammation, promote cell proliferation, and reduce bacterial infections using its superior properties [60], [61], [62], [63], [64].

The main purpose of this work is the fabrication of a curcumin-loaded nanofibrous wound dressing comprised of gelatin and enzymatically synthesized poly(ω-pentadecalactone-co-δ-valerolactone) copolymer which combines the advantages of natural and synthetic polymers. In this context, morphological and molecular structure, wettability characteristics, thermal behavior, curcumin release kinetics, antibacterial activity, and cytotoxicity of the prepared nanofibers have been examined.