A burn, characterized as an injury to the skin or underlying tissues, arises predominantly from exposure to heat, radiation, electricity, friction, or chemical agents. The World Health Organization highlights the global impact of burns, attributing an estimated 265,000 annual deaths, with a disproportionate burden falling on low- and middle-income nations. Despite the severity of burns, the body initiates a natural and intricate response aimed at healing and restoring normal tissue function. This restorative process unfolds through three closely interrelated phases: inflammation, proliferation, and remodeling [1]. When open wounds present excessive tissue loss, the natural process of wound healing is disrupted, necessitating a moist and sterile environment for optimal recovery. Challenges arise with conventional drug delivery methods, including the reliance on critical blood supply for systemic drug delivery, inadequate penetration through the damaged stratum corneum in burned skin, preservation of cell viability post-delivery, and the inability to sustainably release drugs locally at the burn wound site [2,3].

Enhanced comprehension of natural materials has revealed that their exceptional properties are derived from both their chemical elemental composition and their intricate micro/nanostructures at multiple levels [4]. Nanomaterials, inspired by natural phenomena like spider silk and cotton candy, offer avenues for engineering materials with desirable properties, showing the potential for biomimicry to advance medical interventions and material science alike [4,5]. Nanofibers (NFs) fabricated via electrospinning surpass other dressings such as hydrogels, decellularized porcine dermal matrix, and freeze-dried or gas-foaming formed scaffold, as they possess the capability to mimic the intricate architecture of the skin's extracellular matrix (ECM) [5]. Their higher surface area to volume ratio enables enhanced exposure of drug molecular chains to the NFs, thereby facilitating heightened opportunities for binding and catalytic interactions conducive to efficient wound healing across all phases [6]. The selection of polymers for electrospun NF fabrication encompasses a diverse range, including synthetic organic polymers, biopolymers, and blends [5]. Poly(ε-caprolactone) (PCL) is notable for its semi-crystalline biocompatibility and biodegradability, resembling polyolefins in mechanical properties and polyesters in hydrolyzability, with FDA approval for biomedical use [7]. Additionally, natural polymers like collagen, a key structural protein in the ECM, are favored for their water affinity, low antigenicity, weak cytotoxic and inflammatory reactions, great abundance, and overall biological superiority, making them appealing for tissue engineering applications [5]. Taking cues from the hierarchical structure of natural trees, tree-like structured NFs have gained attention for their potential in enhancing functionality and performance. Utilizing trunk fibers for robust skeletal support and branch fibers for increased surface area, similar to the structure of trees, enhances mechanical strength and reduces pore size [4,8]. Investigating variables like salt type and processing parameters is crucial for optimizing NF morphology and overall performance [9,10]. To our knowledge Different studies have reported the success combination of the PCL-Coll (PCLC) NFs along with their biocompatibility [[11], [12], [13]]. The scaffolds are conventional electrospun membranes comprising single-type fibers, known as backbone fibers. However, the objective of this study is to create a heterogeneous scaffold incorporating backbone fibers alongside spider-web-like nano-nets. This new approach aims to evaluate the feasibility of using such scaffolds for wound healing applications.

It is widely acknowledged that alongside engineering an effective drug delivery scaffold, the selection of the drug itself plays a crucial role in regulating the wound healing process throughout different phases. Synthetic drugs, while beneficial in burn wound healing, are often associated with adverse effects such as tissue irritation, redness, pain, gastrointestinal disturbances, discoloration, and dysgeusia [1]. For instance, povidone-iodine ointment may lead to iodine absorption, elevating serum and urine levels [14], while mafenide acetate can induce metabolic acidosis, particularly in larger areas, posing life-threatening risks [15]. Consequently, researchers are increasingly exploring phytochemical constituents and therapeutic agents derived from natural sources. These natural alternatives show promise in effectively promoting burn wound healing across various stages, with a lower risk of adverse effects. Hence, NFs loaded with anti-histamines, antibacterial, bacteriostatic, antispasmodic, and anti-inflammatory agents can offer relief and aid in burn wound healing [1]. Propolis (Pro), a natural substance sourced from bees, stands out for its intricate composition and wide-ranging biological effects [16]. Comprising about 91 % oil, 5 % pollen, and 4 % polyphenolic organic compounds, its chemical complexity is evidenced by the isolation of over 300 bioactive compounds. Notable among its constituents are phenolic compounds, esters, flavonoids, terpenes, steroids, aromatic aldehydes, and alcohols. Particularly, flavonoids such as rutin, quercetin, and naringenin, along with phenolic acids, play significant roles in its biological properties [17].

Various combinations of NFs, including polyvinyl alcohol (PVA) and PCL [17], polyethylene oxide (PEO) [18,19], PCL/chitosan [20], PVA [21], and polyurethane (PU)-hyaluronic acid (HA) [22], embedded with propolis, have been extensively investigated for their potential to enhance biological properties, but no study has been conducted by the authors focusing on blending propolis extract with PCLC NFs. The first question to be addressed is whether modifying the PCLC NF into a novel spider-like structure could enhance its nanofibrous structure, hydrophilicity, and biological properties. Additionally, the extent to which the polymeric engineered structure properties are affected by the propolis extract in the blended matrix needs to be explored.

The third question poses whether the collective properties of the PCLC containing Pro (PCLC/Pro) NFNs could present a groundbreaking advancement in wound healing, potentially establishing them as a novel and effective scaffold for this purpose. To address these questions, experiments such as morphology assessment, release behavior of Pro, porosity, water vapor transmission rate (WVTR), water uptake capacity, and biological assessments including blood compatibility, cytoprotective effects, cytotoxicity, and cell attachment were conducted.