Wounds can be classified into two types based on their duration: acute wounds and chronic wounds. Acute wounds, such as surgical wounds, traumatic wounds, and burns, heal rapidly. Chronic wounds, on the other hand, deviate from the normal healing process and persist for more than 3 months. Examples include pressure ulcers, leg ulcers, and diabetic foot ulcers, which require a longer time to heal. General wound healing involves a series of interconnected and complex processes, involving immune cells, formation cells, as well as the cell factors, chemotactic factors, and growth factors they secrete, which coordinate all stages of healing. Traditionally, wound healing is divided into four consecutive stages: hemostasis following skin injury, an inflammatory response lasting several days, tissue regeneration lasting several days to 1 month, and tissue remodeling, as shown in Figure 2A. However, chronic wounds often stall before reaching the late healing stage (Liang et al., 2022).

The first stage of normal wound healing is hemostasis, during which the body rapidly contracts blood vessels through a nerve reflex mechanism to prevent excessive blood loss caused by vascular damage (Sinegre et al., 2019). Blood platelets play a vital role in hemostasis and clotting. They immediately aggregate upon receiving signals from the extracellular matrix (ECM) (Maouia et al., 2020). The ECM then secretes proteins, such as fibronectin and collagen, which attach to platelet receptors and form blood clots (Rojano et al., 2019). Blood clots are specialized structures composed of platelets embedded in various proteins, crucial for preventing bleeding (Yang et al., 2019; Zeng et al., 2020). In the subsequent 1–3 days, the wound enters the inflammatory response phase, during which neutrophils and anti-inflammatory macrophages gradually differentiate at the site of injury (Behm et al., 2012; Decker et al., 2016). These cells are capable of engulfing bacteria that cause infection and removing damaged cellular debris. During the tissue regeneration phase of wound healing, keratinocytes, fibroblasts, macrophages, and endothelial cells differentiate to re-epithelialize cells, reconstruct vascular tissues, and promote fiber proliferation (Lau et al., 2009; Pan et al., 2021). This stage is characterized by the presence of immune cell subsets that facilitate healing, including M2 anti-inflammatory macrophages and regulatory T cells (Tregs). The tissue remodeling stage typically lasts for 1 month but can extend for several months or even years. It primarily involves fibroblasts, which utilize fibrin protein clots to form scar tissue, accelerate neovascularization, and reshape collagen composition (Hinz, 2016). The entire process of normal wound healing begins with platelet aggregation, which forms blood clots at the wound site and secretes bioactive factors to promote immune cell differentiation and maintain blood vessel permeability. Neutrophils and inflammatory macrophages remove bacterial infections, debris, and dead cells through phagocytosis. Subsequently, the pro-inflammatory immune response transitions into a healing-promoting immune response, reducing inflammation and initiating the process of skin tissue remodeling.

Diabetic wounds, including chronic wounds, deep wounds, infected wounds, and ulcer wounds, are characterized by persistent inflammation, recurrent infections, impaired angiogenesis, impaired tissue epithelialization, and excessive levels of matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) (Holl et al., 2021).

Diabetic wounds are one of the three major types of chronic wounds, with the other two being vascular ulcers and pressure ulcers. The hemostatic and inflammatory stages of chronic wound healing are similar to the normal wound healing process. However, unlike other chronic wounds, diabetic neuroischemic lesions and peripheral vascular lesions can significantly impact wound healing. Additionally, there is often a persistent external wound infection, which hinders the transition from the inflammatory response stage to the tissue regeneration stage, thus slowing down the overall healing process (da Silva et al., 2019).

Diabetic complications are commonly accompanied by vascular lesions, leading to nutritional deficiencies in wound healing. The hypoxic environment of the wound further complicates angiogenesis, and the wound remains in a chronic state of inflammation (Peng et al., 2021). During general wound healing, fibroblasts, keratinocytes, and immune cells secrete MMPs under the influence of local mediators. These mediators, such as transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and interleukins, are essential for tissue epithelialization and regeneration. However, in the high glucose environment of diabetes, the activation of the extracellular regulated protein kinases/activating protein-1 (ERK/AP1) signaling pathway can lead to excessive production of MMPs, resulting in rapid degradation of the extracellular matrix (ECM) (Roep et al., 2019). This affects the adhesion of fibroblasts to the ECM, hindering the regeneration of skin tissue. Activated neutrophils can produce large quantities of matrix metalloproteinase 9 (MMP-9), further impeding the repair of diabetic ulcers (Nguyen et al., 2018). Under normal circumstances, macrophages transition from the M1 type that promotes inflammation to the M2 type that promotes wound repair under the influence of signaling factors, thus reducing inflammation. However, in diabetic wounds, macrophages fail to differentiate into the M2 type and instead produce pigment epithelium-derived factor (PEDF), which inhibits neovascularization. Additionally, neutrophils and M1 macrophages persist in the wound, sustaining inflammation and hindering the regeneration of skin tissue. Moreover, the high blood glucose environment in diabetic wounds promotes bacterial proliferation, leading to recurrent infections (Schreml et al., 2010).

Over time, diabetes can lead to microvascular and macrovascular complications, causing significant pain and suffering for patients. These complications are important factors in the development and progression of diabetic foot ulcers (DFUs). Additionally, immune damage, reactive oxygen species (ROS) production, and bacterial infections also contribute to the development of DFUs (Madhukiran et al., 2021). Diabetic neuropathy (DN) is another complication that can lead to the development of DFUs in diabetic patients (Feldman et al., 2019). The hyperglycemic environment in diabetes often disrupts the arrangement of Schwann cells and axons, leading to impaired peripheral nerve function in DN patients. This disruption also affects the microcirculation of the limbs, resulting in additional nerve damage and loss of foot pain perception (Gumy et al., 2008). The absence of pain sensation makes patients unaware of wounds or ulcers, leading to their enlargement and subsequent infection (Feldman et al., 2019). DN can damage axons, disrupt foot circulation, cause peripheral arterial disease (PAD), and further worsen the condition (Megallaa et al., 2019, p. 2).

During the inflammatory response stage of DFUs, the phagocytic function of macrophages is impaired, resulting in an abundance of M1 macrophages and a prolonged inflammatory state in diabetic wounds. This leads to continuous release of matrix metalloproteinases (MMPs) and rapid degradation of collagen and the extracellular matrix (ECM) (Zhao et al., 2017). Furthermore, the polarization of M1 macrophages slows down the rate of re-epithelialization (Huang et al., 2019). DFUs produce excessive reactive oxygen species (ROS), leading to increased oxidative stress (Singh et al., 2008). These excess ROS react with nitric oxide (NO) to generate peroxynitrite anion (NO₂ ⁻), which interferes with wound healing (Sadati et al., 2018). Moreover, in a hyperglycemic environment, the increased ROS levels promote the formation of advanced glycation end products (AGEs) (Kim and Kwon, 2014). Additionally, hyperglycemia increases glycosylation and enhances intercellular interactions in keratinocytes, resulting in delayed wound closure (Huang et al., 2017) (shown in Figure 2B).

Early control in the development of DFU is crucial for successful treatment, similar to many critical illnesses. Traditional wound healing strategies can be categorized into four aspects: unloading, blood glucose control, debridement, and infection management.

DFUs typically occur in high-pressure areas of the foot, underscoring the importance of pressure redistribution (unloading) during DFU therapy. Various methods can be employed to reduce stress, including the use of canes, wheelchairs, surgical interventions, surgical shoes, bandages, and more. Total Contact Castings (TTC) made from specialized materials are widely regarded as the most effective method for unloading during the DFU healing process. Compared to dressings, TTCs have been shown to significantly shorten the healing time of DFUs (Sahu et al., 2018). However, TTCs also have notable disadvantages. They require the expertise of well-trained staff and patient compliance can be poor. In many cases, they cannot be successfully removed, and improper use can even worsen the condition.

Long-term hyperglycemia in diabetic patients can have a detrimental impact on DFU healing, making glycemic control necessary. Glycemic control is typically achieved through medication and a controlled diet to maintain normal blood glucose levels.

Debridement is an essential component of standard DFU care, as it promotes wound healing by removing necrotic tissue and reducing bacterial biofilm and excess matrix proteins. Various types of debridement exist, with surgical debridement being the most commonly used. However, one must be cautious with debridement as it requires time and multiple procedures to yield positive therapeutic effects. A slight oversight can lead to the rapid and severe progression of diabetic foot conditions.

In patients with DFUs who progress to the point of requiring amputation, the ulcerated area often presents with severe infection (Huang et al., 2022b). This is primarily due to the prolonged exposure of the wound in diabetic patients. Infections are typically managed with orally administered antibiotics, which pose significant limitations to treatment (Zhang et al., 2023). High antibiotic concentrations can have serious side effects on the human body. Therefore, it is imperative to explore new strategies for DFU treatment and management (Hu et al., 2021).

The treatment of diabetic wounds and DFUs involves debridement, improved glucose regulation, infection control, and the use of moist dressings to facilitate wound healing and restore blood supply (Tottoli et al., 2020). However, when these traditional treatments prove inadequate, new therapeutic approaches are sought. In recent years, our understanding of diabetic wounds has expanded, paving the way for the development of novel multi-functional wound scaffolds (Al-Dhahebi et al., 2022; Yu and Zhao, 2022; Si et al., 2023).

Among these approaches, electrospinning technology is noteworthy. It is a well-established process for fabricating nanofibers (Wang H et al., 2023), with a history spanning several centuries. By carefully adjusting the process parameters of the electrospinning equipment (such as receiving distance, voltage, and flow rate), environmental variables (including humidity and temperature), and polymer solution variables (such as viscosity, solution electrical conductivity, capillary force, molecular weight, and polymer type), electrospun nanofibers with desirable physical properties and excellent structures can be obtained. Electrospinning equipment typically consists of four components: a high voltage power supply, an injector, a spinning nozzle, and a receiving screen (as illustrated in Figure 3). The underlying principle involves applying an electrostatic field of tens of thousands of volts between the injection device and the receiving device, resulting in the formation of a jet from the tapered end of the spinning solution. This jet is then stretched within the electric field and ultimately forms a nonwoven nanofiber structure on the receiving device (Kang et al., 2020).

One of the main advantages of electrospinning is the ability to create highly porous fiber structures that mimic the extracellular matrix (ECM) and that aid in wound healing (Sell et al., 2010). this makes it an excellent choice for the fabrication of DFU therapeutic scaffolds (as shown in Table 1). By optimizing the processing and environmental parameters of electrospinning, the porosity and pore size of the scaffolds can be tuned to promote diffusion. This porous structure facilitates gas exchange at the wound site and can also serve as a platform for drug loading, allowing for controlled drug release through structural adjustments (Samadian et al., 2020).

The constructed scaffold exhibits a high specific surface area and volume ratio, resulting in increased drug loading capacity and consistent drug release. Moreover, its porous nature promotes wound desiccation, creating an ideal healing environment (Junker et al., 2013). Electrospinning can produce nano-scale scaffold fibers, increasing the surface area available for cell adhesion and facilitating wound healing (Glover et al., 2021).

To effectively treat DFU, it is important to focus on vascularization, collagen accumulation, and normal physiological function. This will help control the deterioration process and promote wound healing (Lv et al., 2017). Although DFU patients often struggle to heal on their own, biomolecules and active drugs, such as antibiotics, can provide much-needed assistance. Electrospun nanofiber scaffolds are an excellent platform for carrying active drugs due to their controlled-release capabilities. Additionally, nanofiber scaffolds can positively influence exudate uptake and exchange of oxygen, water, and nutrients, which are vital activities in wound healing (Kim et al., 2012).

Different types of electrospun scaffold structures require specific preparation methods, including single-fluid and two-fluid electrospinning, as well as the emerging multifluid electrospinning (as shown in Figure 4). Scaffolds prepared using these methods possess unique advantages for wound healing applications. For instance, Ren et al. (Han et al., 2019) investigated the role of oriented scaffolds prepared by single-fluid electrospinning in wound healing and observed a significant enhancement in cell adhesion. Ahmed et al. (Ahmed et al., 2018) developed a zinc oxide (ZnO)-loaded chitosan/polyvinyl alcohol core-shell nanofiber scaffold using electrospinning technology. The antibacterial efficacy and antioxidant potential of both ZnO-loaded and ZnO-free scaffolds were evaluated, demonstrating excellent antibacterial and antioxidant properties. These scaffolds, which exhibited antibacterial properties against both Gram-positive and Gram-negative bacteria, were further tested for wound healing in rats, both with and without cells. The results showed successful wound healing and complete epithelial regeneration (Ranjbar-Mohammadi et al., 2016). Coaxial electrospinning technology was employed to fabricate a core-shell scaffold composed of chitosan and polylactic acid, which improved its mechanical properties and enhanced cell adhesion and proliferation. This scaffold has found applications in tissue engineering (Surucu and Sasmazel, 2016). Furthermore, electrospun scaffolds can be combined with 3D printing techniques to replicate the ECM matrix structure, thereby promoting wound healing in diabetes (Mellor et al., 2017; Zhang et al., 2021).

Uniaxial nanofiber scaffolds are typically prepared through blend electrospinning, where the drug and polymer solutions are mixed and electrospun through a single nozzle. Traditional single-axis electrospinning has garnered significant attention from researchers due to its simplicity, cost-effectiveness, high yield, and ease of operation. However, blend electrospinning also has its drawbacks, as it requires the polymer to be spinnable (Wu et al., 2020). By combining two different polymers through blend electrospinning, uniaxial nanofiber scaffolds can be prepared, inheriting the advantageous properties of both polymers, such as good mechanical properties and biocompatibility. However, it is possible for these scaffolds to exhibit deficiencies in certain properties, which can be improved by incorporating additional polymers or utilizing physical techniques such as cross-linking or lyophilization.

For instance, Lv et al. (2022) successfully fabricated a series of blend electrospun nanofibers by combining chitosan (CS) and polyvinyl alcohol (PVA) with the addition of ursolic acid (UA). The resulting CS-PVA-UA nanofiber scaffolds exhibited a morphology resembling collagen fibers in the natural skin extracellular matrix, along with excellent surface hydrophilicity, wettability, and hemostatic properties. The addition of UA to CS-PVA nanofibers also demonstrated good biocompatibility and drug release properties. In vivo experiments conducted on diabetic mice showed that the nanofiber scaffold effectively inhibited inflammation and oxidative stress, promoted angiogenesis, collagen deposition, epithelial formation, and hair follicle regeneration, ultimately achieving wound healing. Gholipour-Kanani et al. (2016) prepared chitosan-polyvinyl alcohol nanofiber scaffolds, and subsequently incorporated polycaprolactone (PCL) to enhance mechanical and biological properties. These scaffolds were tested in both a diabetic rat back skin wound model and a diabetic foot ulcer wound model. The results showed significant reduction in wound area and increased new granulation tissue formation in rats treated with the nanofiber scaffolds. Complete wound closure was achieved within 20 days of resection. The addition of PCL improved the mechanical and biological properties of the scaffolds.

El-Lakany et al. (2020) introduced a copper-grafted graphene oxide cross-linked zein electrospun scaffold (Cu-GZS) for promoting healing of skin excision wounds in diabetic male rats. Graphene oxide enhanced mechanical stability and swellability of the scaffold, and copper ions were incorporated as a bactericide and angiogenesis promoter. The optimized Cu-GZS exhibited a constant copper release rate and accelerated wound closure, as evidenced by reduced leukocyte infiltration, intact epithelium with normal keratinization, and faster wound size reduction. Guo et al. (2022) developed a nanofibrous scaffold composed of marshmallow polysaccharide (EPP1) and polyvinyl alcohol (PVA), which exhibited excellent water absorption and anti-inflammatory activity. In vitro and in vivo experiments demonstrated that PVA/EPP1 fiber scaffolds accelerated wound repair in diabetic mice. Kellar et al. (2020) investigated the synthesis of electrospun biomimetic scaffolds containing Tropoelastin (TE) and collagen. In vivo experiments using a diabetic mouse model revealed that the scaffold group exhibited increased neoplastic skin tissue, faster wound healing, reduced inflammatory response, and closer resemblance to unwounded skin compared to the control group. Jintao (2022) prepared PVA/calcium alginate scaffolds through blend electrospinning and loaded idebenone at different concentrations for diabetic wound healing. The scaffold loaded with 1% idebenone demonstrated the best performance. In vivo evaluation using a rat diabetic wound model showed that the scaffold group achieved the fastest wound closure rate. Histological immunostaining experiments revealed that the scaffold promoted new skin formation while reducing oxidative stress and inflammation.

Due to the limitations of uniaxial nanofiber scaffolds, it is difficult to prepare more complex nanostructures. As a result, a multi-fluid electrospinning technique has been developed, in which two or more solutions are pushed into a spinneret using various syringes for electrospinning. The main types of multi-fluid electrostatic spinning processes are coaxial electrostatic spinning, side-by-side electrostatic spinning, and triaxial (three-layer coaxial, three-layer side-by-side) electrostatic spinning.

Among the various electrospun nanofibers, the core-shell nanofiber is the most widely used (Rathore and Schiffman, 2021). Compared with other nanofibers (as shown in Table 3), the core-shell nanofiber scaffold can delay drug release and reduce its severity (Wang Y et al., 2023; Chen et al., 2024; Duan et al., 2024). To prepare nanofiber scaffolds with a core-sheath structure, two spinnerets of different apertures are used to nest into a concentric circle-like spinneret. The drug is loaded into the core layer, and the shell layer can slow down the release of the drug. Additionally, two different drugs can be loaded in this core-shell structured nanofiber, and the drugs can be released sequentially. The advantages of the core-shell type nanofiber structure are that it can achieve different sustained-release or quick-release effects based on the adopted macromolecules, and it can conveniently meet the transportation requirements of different drug (Han and Steckl, 2019). Therefore, it is considered to be one of the important breakthroughs in the drug delivery system (Pant et al., 2019; Yu and Huang, 2023). Yan et al. (2020) prepared a PVA/PCL core-shell nanofiber scaffold loaded with doxorubicin (DOX) using electrospinning technology and achieved continuous release of DOX in response to pH by utilizing the sensitivity of PVA to pH.

Lee et al. (2020a) developed insulin-loaded poly-D-L-lactic-co-glycolic acid (PLGA) core-shell nanofiber scaffolds that can stably release insulin to reduce blood sugar and aid in diabetic wound healing. They placed PLGA and insulin solutions into two syringes and electrospun them through two different injection pumps. The prepared scaffold releases insulin for up to 4 weeks. Additionally, the hydrophilicity of the core-shell scaffold is better than that of the mixed nanofiber scaffold. Gene expression detection showed that compared with the control group, type I collagen decreased and transforming growth factor-β increased in the scaffold group. This demonstrates the benefit of the core-shell scaffold, which allows for the delayed release of medication and aids in wound healing. Augustine et al. (2019) developed an electrospun dual porous polylactic acid/polyvinyl alcohol (PLA/PVA) nanofiber scaffold loaded with connective tissue growth factor (CTGF). CTGF was loaded into the polyvinyl alcohol sheath. The scanning electron microscope (SEM) results showed high porosity in the scaffold with secondary pores on the surface of many single fibers. Cell experiments demonstrated that PLA/PVA scaffolds have high biocompatibility and biosafety. The drug release curve also showed stable release of CTGF. Chicken chorioallantoic membrane (CAM) experiments further demonstrated that the scaffolds can help with vascular remodeling. Lee et al. (2020b) developed a PLGA nanofiber core-shell scaffold loaded with antibiotics and platelet-derived growth factor (PDGF). In this scaffold, PDGF acts as the outermost shell, while the core layer consists of a mixture of PLGA and vancomycin. Drug release experiments showed that the scaffold could stably release PDGF and antibiotics for up to 3 weeks. In vivo experiments showed that the scaffold enhanced neovascularization around the wound area.

Gupta and Wilkes published the first study on the fabrication of Janus nanofibers by side-by-side electrospinning in 2003 (Gupta and Wilkes, 2003). Side-by-side electrostatic spinning involves combining two spinnerets side-by-side to prepare Janus fibers made of two materials that can both come into direct contact with the environment (Li et al., 2019; Lv et al., 2023a; Lv et al., 2023b). Zheng et al. (2021) used a side-by-side electrospinning procedure to create two Janus nanofiber scaffolds. The first scaffold combined tamoxifen citrate (TAM) as the medicine and ethylcellulose (EC) as the polymer carrier matrix. The second scaffold, TAM-PVP, used TAM as the medication and polyvinylpyrrolidone (PVP) K60 as the polymer carrier matrix. Due to differences in PVP and EC solubilities, drug release tests demonstrated that biphasic drug release was feasible for the two groups of fibers. However, the drug release characteristics of the two fiber groups differed dramatically. During the initial stage of drug release, TAM-PVP demonstrated a more rapid burst release and a slower sustained release in the subsequent phase, whereas TAM-EC exhibited the opposite pattern. This demonstrates the effectiveness of the Janusnanofiber scaffold in achieving different drug release profiles (Hussein et al., 2022).

Multifluid electrospinning, including the trifluid electrospinning method, is an advanced technique that enhances the electrostatic spinning process by incorporating multiple solutions. One notable application of this technique is the fabrication of core-shell nanofibers, which holds great potential for the treatment of diabetic wounds (Zhou et al., 2023c). In trifluid electrospinning, three fluids are simultaneously electrospun, resulting in nanofibers with a gradient structure consisting of three layers. The medication is typically loaded in the innermost layer, ensuring controlled and uniform release of the drug (Huang et al., 2022a). As a result, the release rate remains constant, eliminating the possibility of abrupt or excessive drug release. In a study conducted by Nagiah et al. (2020), a novel and robust trifluid electrospun fibrous scaffold was developed with dual drug delivery capabilities. The scaffold consisted of a core layer made of PCL, a middle layer composed of gelatin loaded with bovine serum albumin (BSA) as the therapeutic drug, and a shell layer made of PLGA loaded with rhodamine B (RHB). The resulting nanofibers exhibited superior mechanical properties and drug release capabilities compared to both uniaxial and coaxial fibers. Ding et al. (2020) employed a modified triaxial electrospinning technique to fabricate core-shell nanofibers using Eudragit S100 (ES100) as the base material, which was loaded with aspirin. The in vitro drug release experiments demonstrated that these nanofibers exhibited a stable and sustained release of the drug, thereby avoiding the risk of excessive administration. In a similar vein, Wang et al. (2020) developed a novel approach for the preparation of three-layer nanoreservoirs and the construction of three-level core-sheath nanofibers. The drug components comprised cellulose acetate and acyclovir (ACY). The drug release profile exhibited a consistent and controlled release of ACY throughout the testing period. Derakhshan et al. (2022) conducted a study on a three-layer electrospun scaffold composed of PCL, PCL/collagen, and collagen. The collagen layer was supplemented with lignocaine extract, known to enhance the healing of diabetic wounds by promoting vascularization. Scanning electron microscopy analysis confirmed the favorable morphology of the nanofibers. In order to evaluate the wound healing efficacy of the fabricated scaffolds, streptozotocin-induced diabetic rats were employed as an animal model. The three-layer electrospun scaffolds containing lignocaine extracts exhibited the highest mean wound closure diameter among the tested groups, surpassing PCL, PCL/collagen, and pure collagen. These findings indicate that the herbal extracts did not affect the physical properties of the scaffolds, but significantly augmented their bioactivity, making them valuable for the treatment of diabetic ulcers (in Figure 5).

Specially structured nanofibers exhibit various arrangements, including random orientation (Inai et al., 2005), oriented-ordered structure (Kong et al., 2014), micropatterned structure (Kakunuri et al., 2017) and spider-web-like structure (Kim et al., 2013). These unique fiber structures offer advantages such as excellent adsorption capacity and stable mechanical properties.

Sun et al. (2018) observed a distinctive basketweave-like structure in collagen fibrils of natural skin. Inspired by this, they fabricated biomimetic nanofiber scaffolds with crossed fiber organization via electrospinning. Cell growth experiments comparing the crossed nanofiber scaffolds with aligned and random nanofiber scaffolds were conducted. The results demonstrated that the crossed nanofiber scaffold exhibited superior biocompatibility, enhanced cell growth, and improved cell adhesion compared to the other two groups. Using a diabetic rat wound model, the wound healing effects of the three nanofiber scaffold groups were compared. All three scaffold groups displayed better wound healing than the control group, but the crossed nanofiber scaffold group exhibited the fastest wound closure speed and the most favorable healing state. Additionally, the crossed nanofiber scaffold group exhibited a higher density of newly formed blood vessels.

Sanhueza et al. (2021) developed a dual-size nanofiber scaffold composed of two polymer materials: poly-3-hydroxybutyrate (PHB) and gelatin (Ge). Ge improved the biocompatibility of the scaffold, while PHB crosslinked with Ge, enhancing the mechanical properties and porosity of the scaffold. In cell biological experiments, the double-sized Ge-PHB fiber scaffold effectively promoted fibroblast adhesion, re-epithelialization, and exhibited a slow degradation rate as expected. Furthermore, in vivo data demonstrated that the Ge-PHB scaffold resulted in a larger wound healing area, faster wound closure rate, increased formation of new skin tissue, and greater neovascularization content.

Wang J et al. (2022) developed a three-dimensional biomimetic nanofiber scaffold using electrospinning technology and surface modification. The scaffold was designed to collect early biofluids and respond to endogenous electric fields (EF). It exhibited high hydrophilicity and was composed of a polymer matrix of polydopamine and reduced graphene oxide, providing exceptional mechanical properties. The scaffold’s structure functioned as an “electronic skin,” facilitating wound gas exchange, absorbing wound exudates to generate endogenous bioelectricity, and promoting diabetic wound healing.

Jiang et al. (2019) fabricated spacer-oriented nanofiber scaffolds with silicon-doped amorphous calcium phosphate nanocoatings (Si-ACP) on the surface using electrospinning. The substrate materials of the electrospun scaffolds were poly (D, L-lactic acid) (PDLLA) and polycaprolactone (PCL). Scanning electron microscopy (SEM) analysis revealed a random orientation of the nanofibers, with only a small portion exhibiting porosity. The Si-ACP particles were uniformly distributed on the fiber surface. Drug release experiments demonstrated stable release of silicon ions. In vitro cellular investigations confirmed the biocompatibility of the scaffolds and their ability to promote cell development. In vivo studies utilizing a diabetic mouse wound model showed that compared to a control group using a commercially available dressing, the scaffold group exhibited enhanced wound healing and accelerated neovascularization.

Zhang et al. (2020) utilized coaxial electrospinning to fabricate a specially designed nanofiber scaffold coated with bioglass nanoparticles for improving the healing of diabetic wounds. The therapeutic mechanism of the scaffold involved the controlled release of silicon and calcium ions from the bioglass, which promoted the production of biological factors associated with vascular remodeling in the wound. Additionally, the scaffold’s unique patterned structure provided a larger surface area for fibroblast growth and adhesion, facilitating wound closure. In vivo experiments demonstrated that the use of the scaffold increased the number of new blood vessels in the wound and significantly improved the wound closure rate. Furthermore, they prepared an oriented poly (L-lactic acid) (PLLA) fiber scaffold loaded with asiatic acid (AA) through blend electrospinning (Ren et al., 2018). The resulting nanofibers exhibited a porous structure, with AA molecules evenly distributed on the fiber surface. The scaffold exhibited excellent biocompatibility and could regulate cytokine genes involved in macrophage differentiation. In vivo experiments using a diabetic mouse wound model showed that compared to the control group, the scaffold group reduced ROS content at the wound site and promoted new skin formation, vascular remodeling, and extracellular matrix (ECM) formation.

Jiang et al. (2020) developed a micro-patterned scaffold by electrospinning and polydopamine coating, loading spherical bioactive glass on the surface. The scaffold matrix material was poly (ε-caprolactone) (PCL). The spherical bioactive glass was uniformly dispersed on the nanofiber surface, enabling stable release of calcium and silicon ions. In vitro experiments demonstrated that the scaffold had the potential to promote proliferation and vascular differentiation of human umbilical vein endothelial cells. Further in vivo experiments showed that the polydopamine-coated patterned scaffold efficiently promoted the healing of diabetic wounds by enhancing re-epithelialization and collagen deposition. Moreover, the deliberate release of silicon ions from the scaffold had the potential to enhance angiogenesis and suppress inflammation at the wound site, ultimately improving diabetic wound healing.

Su et al. (2020) developed a novel nanofiber scaffold for eradicating bacterial biofilms in diabetic wounds. The scaffold consisted of two components: an electrospun nanofiber scaffold and a soluble microneedle array. The scaffold effectively delivered self-designed antimicrobial peptides both inside and outside the biofilm, resulting in the resistance against a wide range of pathogens. In vivo results demonstrated the complete elimination of methicillin-resistant Staphylococcus aureus (MRSA) and resistance against Pseudomonas aeruginosa by the scaffold.

Currently, conservative treatment options, including drug therapy, are commonly used for patients with diabetes mellitus. Electrospun scaffolds serve as excellent drug-loading platforms, enabling the loading of various conventional drugs for diabetes treatment, such as antibiotics, hypoglycemic drugs, anti-inflammatory drugs, and natural drugs. They can also accommodate bioactive factors, inorganic nanoparticles, specialized biological cells, and other substances that have limited applicability in conventional treatments. Furthermore, in cases where a single drug may not provide optimal wound healing outcomes, electrospun scaffolds can be loaded with multiple drugs, leading to a synergistic therapeutic effect.