Wound healing is one of the major challenges in medicine. Wound care aims to accelerate wound healing and relieve pain. New and effective biomaterials are required for wound dressings and skin grafts to facilitate wound healing (Liu et al., 2023, Gupta et al., 2022, Bazli et al., 2020). Briefly, exogenous injuries to the skin result in wounds that are discontinuities in tissue. Chronic wounds take longer to heal, so they are vulnerable to bacterial infection (Karahaliloglu et al., 2017, Rahmani Del Bakhshayesh et al., 2018). Moreover, wounds are becoming an increasingly common health issue. For example, diabetes, a lifestyle disorder, increases the risk of wound complications. Furthermore, the intricate nature of the healing process can make it challenging to treat these wounds effectively (Sahana and Rekha, 2018, Yang et al., 2020). Bioactive polymers tend to outperform traditional wound care methods in wound treatment. The skin is a multilayered tissue, which accounts for its distinct geometry (Keirouz et al., 2020, Alam et al., 2021). Despite the fact that the use of skin substitutes for wound healing has progressed significantly in recent years, and various dermo-epidermal skin substitutes are being thoroughly investigated for clinical application (Keirouz et al., 2020, Milan et al., 2019), the market does not yet offer full-thickness functional artificial skin (Liu et al., 2023, Hao et al., 2023). Skin tissue engineering is one of the most appealing wound healing strategies among researchers. Precisely, skin tissue engineering encompasses creating scaffolds that mimic natural tissue and promote efficient regeneration (Franco et al., 2013, Wang et al., 2023). Wounds with excessive skin loss require tissue-engineered biomaterials to cover and stimulate tissue repair. The ideal dressing should emulate the original skin structure and function. The scaffold in skin tissue engineering applications needs to protect the wound bed from fluid loss, aid in exudate removal, and defend against infectious agents (Kumbar et al., 2008). Nanofibers, which resemble the natural extracellular matrix (ECM), are potent among the scaffolds that are currently available. Moreover, nanofibers have surface modification ability, skin-like mechanical properties, large number of pores, high surface/volume ratio that promotes cell growth, and high permeability. Various techniques, including electrospinning, phase separation, self-synthesis, drawing, and template synthesis can be employed to synthesize nanofibers (Asl et al., 2022, Zamani et al., 2020). Electrospinning is a recognized technique for manufacturing nano and microfibers by optimizing the process parameters and polymer solution’s variables (Alam et al., 2021, Asl et al., 2022, Shahriari-Khalaji et al., 2023). The high surface/volume proportion of nanofibrous scaffolds provides more surface area for cell adhesion (Shahriari-Khalaji et al., 2023, Subramanian et al., 2012). To date, various polymers, such as artificially synthesized degradable and non-degradable polymers and natural polymers, have been electrospun to fabricate nanoscale fibrous membranes for skin tissue engineering (Mo et al., 2015, Norouzi et al., 2015). For instance, keratin (Kr) is the primary biocompatible and biodegradable protein found in animal hair and wool fibers (Sanchez Ramirez et al., 2022, Yang et al., 2023). Additionally, Kr-based materials work with the proteolytic wound environment to speed up the healing process, making them suitable for chronic wound dressings (Yao et al., 2017, Kiani et al., 2017). Kr has been validated in recent studies to support the adherence and development of several cell morphologies, including fibroblasts. (Ferraris et al., 2017), osteoblasts (Li et al., 2009), neuroblasts, and keratinocytes (Feroz et al., 2020, Costa et al., 2018). Moreover, several cell adhesion sequences that are also present in ECM proteins such as fibronectin are also found in Kr protein fibers, including arginine-glycine-aspartic acid (RGD) and leucine–aspartic acid–valine (LVD) (Yao et al., 2017, Verma et al., 2008). The existence of these sequences enables Kr to enhance cell attachment and propagation. The aforementioned benefits render Kr appealing as a tissue engineering construct (Tachibana et al., 2002, Katoh et al., 2004), nevertheless, the brittleness of Kr-based scaffolds limits their applicability (Marshall et al., 1991). Due to its low molecular weight and brittleness, Kr is challenging to electrospin into nanofibers. Various researches have reported the electrospinning of Kr blended with poly(ethylene oxide) (Sanchez Ramirez et al., 2022), Silk fibroin (Zoccola et al., 2008), polyamide 6 (Aluigi et al., 2011), and poly(lactic-co-glycolic acid) (Zhang, 2011). As a result, some studies combined Kr with other polymers to fabricate novel and effective wound dressings with enhanced properties (Yao et al., 2017). Plants are proven in the traditional wound healing strategies (Pereira and Bartolo, 2016). The natural compounds found in medicinal plants have potential to influence inflammation, coagulation, collagenization, epithelialization, and wound contraction. These compounds also facilitate in immunoregulation and reduce inflammation (Das et al., 2016, Moeini et al., 2020). One of the effective strategies to deal with the problems associated with wound treatment is to make novel wound dressings by combining medicinal plant components with natural or synthetic polymers. These active components may have anti-inflammatory, antimicrobial, and antioxidant properties, which benefit wound constriction, angiogenesis, and epithelialization (Liang et al., 2021, Gaspar-Pintiliescu et al., 2019). Many investigators have recently become interested in the therapeutic benefits of Aloe vera (Alo), adding it to wound dressings to increase their effectiveness (Liang et al., 2021). However, since Kr and Alo are both natural polymers with inherently poor mechanical properties. Consequently, the mechanical characteristics can be improved by using the Polymer polyacrylamide (PAAm). PAAm, a cationic polymer with high swelling ratio and water absorption ability, provides an ideal substrate for wound healing, by absorbing wound exudates, secreting bioactive agents, and keeping the wound moist (Mirhaj et al., 2022). In addition to maintain moisture, adhesion, and cell proliferation, which are critical factors in the design of a wound dressing, the capacity of a wound dressing to induce angiogenesis for waste removal and the exchange of gases and nutrients at the defect site is critical. L-arginine (L-Arg), is an amino acid possessing a guanidine basic chain (Mikeš et al., 2020) that can be transformed into nitric oxide and ornithine at wound site. Ornithine is proline progenitor that is one of the most crucial amino acids in collagen formation, whereas, nitric oxide has antimicrobial activity as well as ability to stimulate angiogenesis. As a result, L-Arg significantly speeds up the healing of wounds (Mirhaj et al., 2022, Sarkar et al., 2023). As previously stated, electrospinning is the most popular method for the development of a nanofibrous scaffolds. One of the most commonly employed methods for creating multipurposeed core–shell nanofibers is the coaxial electrospinning (Tavakoli et al., 2022).

Considering all above-mentioned parameters, herein, we innovatively used coaxial electrospinning technique to fabricate a functional core–shell membrane for wound dressing application. To the best of our knowledge, none of the previous studies employed this structure and materials to fabricate bioactive wound dressings. In the synthesized nanofibrous membranes, the core of nanofibers comprised PAAm and the shell consisted of AloKr, AloKr/L-Arg. We anticipate that the incorporation of PAAm in core would increase the tensile properties and high surface area/volume ratio nanofibers in the shell would promote the release of L-Arg that not only will stimulate angiogenesis and collagen synthesis but also will have an antibacterial effect. Taken all these parameters together, the dressing is expected to accelerate healing rate and trigger angiogenesis.