The high incidence and prevalence of diabetic foot ulcers (DFUs) present a substantial clinical and economic burden, necessitating innovative therapeutic approaches. Fibroblasts, characterized by their intrinsic cellular plasticity and multifunctional capabilities, play key roles in the pathophysiological processes underlying DFUs. Hyperglycemic conditions lead to a cascade of biochemical alterations that culminate in the dysregulation of fibroblast phenotype and function, which is the primary cause of impaired wound healing in DFUs. Biomaterials, particularly those engineered at the nanoscale, hold significant promise for enhancing DFU treatment outcomes. Electrospun nanofiber scaffolds, with their structural and compositional similarities to the natural extracellular matrix, serve as an effective substrate for fibroblast adhesion, proliferation, and migration. This review comprehensively summarizes the biological behavior of fibroblasts in DFUs and the mechanism mediating wound healing. At the same time, the mechanism of biological materials, especially electrospun nanofiber scaffolds, to improve the therapeutic effect by regulating the activity of fibroblasts was also discussed. By highlighting the latest advancements and clinical applications, we aim to provide a clear perspective on the future direction of DFU treatment strategies centered on fibroblast-targeted therapies.

The challenge of healing burn wounds is significant importance in global healthcare systems, with a high demand for advanced wound dressings to aid in the treatment of such injuries. Promising options include bioactive electrospun scaffolds made from polymers with antimicrobial properties, which can prevent infections and promote faster healing. This study involved the creation of a nanofibrous scaffold using the electrospinning technique, which consisted of polyvinyl alcohol (PVA), alginate (Alg), and Dragon's blood (DB). The scaffold was then analyzed for both its morphology and chemical composition. Results indicated that the DB was present in the nanofibrous scaffold, which had a uniform and unbranched appearance with fibers measuring approximately 300-400 nm in diameter. Additionally, mechanical property testing revealed promising results that fall within the range of human skin. The scaffold's wound healing potential was evaluated through various measurements, including water contact angle, drug release, water vapor permeability, blood compatibility, blood clotting index, and antibacterial activity. Results from an in vivo study on burn wounds showed that scaffolds containing 20% DB exhibited excellent wound healing ability with 80.3% wound closure after 21 days. This was attributed to the highest collagen synthesis, re-epithelization and remodeling of the burned skin. Therefore, PVA/Alg/DB nanofibrous scaffolds hold promise as a wound dressing to treat burn injuries.

Sweet clover, particularly white sweet clover (Melilotus albus), is an underexplored plant that has gained attention in recent years. This study compared the bioactive compounds content in the flowers, leaves, and stems of Melilotus albus Medic. to the well-known health-promoting Melilotus officinalis (L.) Lam. Both fresh and dried plant materials were analysed, with chromatographic assessments preceded by the optimisation of the extraction method (using 50% aqueous ethanol-water and the plant sample ground in a mortar, followed by 30 min of ultrasound-assisted extraction). Flower and leaf extracts were also evaluated for their total phenolic content (TPC) and antioxidant activity using FRAP and DPPH· assays. Both plant species were rich in phenolic compounds, including coumarins, phenolic acids, and flavonoids. HPLC-PDA analysis revealed similar profiles for both species, with quantitative differences in individual compound fractions. The highest coumarin content was found in the fresh flowers, followed by the leaves and stems. No significant species-specific differences in the coumarin content were observed. However, the flowers of M. albus were a richer source of flavonoids, with the highest hyperoside content. The flavonoid profile in the leaf extracts was similar to that of the flowers, but the content was about four times lower in the leaves and even lower than in the stems. Interestingly, the leaf extracts exhibited higher antioxidant activity than the flower extracts. The presented findings suggest that white sweet clover is an equally valuable source of health-promoting compounds as yellow sweet clover.

In recent years, a wide variety of high-performance and versatile nanofiber membranes have been successfully created using different electrospinning methods. As vehicles for medication, they have been receiving more attention because of their exceptional antibacterial characteristics and ability to heal wounds, resulting in improved drug delivery and release. This quality makes them an appealing choice for treating various skin conditions like wounds, fungal infections, skin discoloration disorders, dermatitis, and skin cancer. This article offers comprehensive information on the electrospinning procedure, the categorization of nanofiber membranes, and their use in dermatology. Additionally, it delves into successful case studies, showcasing the utilization of nanofiber membranes in the field of skin diseases to promote their substantial advancement.

Wound healing can result in complex problems, and discovering an effective method to improve the healing process is essential. Polymeric biomaterials have structures similar to those identified in the extracellular matrix of the tissue to be regenerated and also avoid chronic inflammation, and immunological reactions. To obtain smart and effective dressings, bioactive agents, such as essential oils, are also used to promote a wide range of biological properties, which can accelerate the healing process. Therefore, we intend to explore advances in the potential for applying hybrid materials in wound healing. For this, fifty scientific articles dated from 2010 to 2023 were investigated using the Web of Science, Scopus, Science Direct, and PubMed databases. The principles of the healing process, use of polymers, type and properties of essential oils and processing techniques, and characteristics of dressings were identified. Thus, the plants Syzygium romanticum or Eugenia caryophyllata, Origanum vulgare, and Cinnamomum zeylanicum present prospects for application in clinical trials due to their proven effects on wound healing and reducing the incidence of inflammatory cells in the site of injury. The antimicrobial effect of essential oils is mainly due to polyphenols and terpenes such as eugenol, cinnamaldehyde, carvacrol, and thymol.

Nanofibers hold significant promise for wound healing applications, but their potential is limited by their large diameter. To overcome this limitation, the development of nanofibrous systems with refined nanonets (approximately 20 nm in diameter) represents a notable improvement. In this study, a composite of polycaprolactone/collagen (PCLC) nano-fiber/nets (NFNs) was fabricated using benign solvents (acetic acid and formic acid) via the electro-spinning/netting (ESN) technique, harnessing the regenerative potential of collagen as a biological macromolecule. Additionally, to enhance the natural attributes of the NFNs structure, Propolis extract, renowned for its wound healing properties, was incorporated. Five ESN solutions were prepared: PCL, PCLC, PCLC/Pro 5 %, PCLC/Pro 10 %, and PCLC/Pro 15 %. NaCl salt was introduced into all ESN solutions to improve nanonets formation. FE-SEM imaging demonstrated successful nano-net formation in all ESN solutions except for the PCL formulation. The fabricated scaffolds exhibited spider-like nanonets with the addition of collagen and further enhanced nano-net formation with Propolis incorporation. Trunk nanofibers showed filamentous structures without any beads, with an average diameter of 164-728 nm, while the diameter of branched fibers (nanonets) was approximately 20 nm. WVTR values of the NFNs were comparable to commercial dressings such as Tegaderm. The results also demonstrated the potent cytoprotective effects of Propolis-loaded NFNs in a dose-dependent manner. Furthermore, the viability of HFF-2 cells after 72 h of culture on PCLC NFNs significantly increased compared to PCL nanofibers. The highest cell viability was observed in PCLC/Pro 15 % nanofibers after 24, 48, and 72 h of cell culture, indicating the proliferative effect of Propolis extract in nanoformulated form. Additionally, the scaffolds exhibited a hemocompatibility of <3 %, further highlighting their potential in wound healing therapeutics.

Diabetic wounds are a significant subset of chronic wounds characterized by elevated levels of inflammatory cytokines, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS). They are also associated with impaired angiogenesis, persistent infection, and a high likelihood of hospitalization, leading to a substantial economic burden for patients. In severe cases, amputation or even mortality may occur. Diabetic foot ulcers (DFUs) are a common complication of diabetes, with up to 25% of diabetic patients being at risk of developing foot ulcers over their lifetime, and more than 70% ultimately requiring amputation. Electrospun scaffolds exhibit a structural similarity to the extracellular matrix (ECM), promoting the adhesion, growth, and migration of fibroblasts, thereby facilitating the formation of new skin tissue at the wound site. The composition and size of electrospun scaffolds can be easily adjusted, enabling controlled drug release through fiber structure modifications. The porous nature of these scaffolds facilitates gas exchange and the absorption of wound exudate. Furthermore, the fiber surface can be readily modified to impart specific functionalities, making electrospinning nanofiber scaffolds highly promising for the treatment of diabetic wounds. This article provides a concise overview of the healing process in normal wounds and the pathological mechanisms underlying diabetic wounds, including complications such as diabetic foot ulcers. It also explores the advantages of electrospinning nanofiber scaffolds in diabetic wound treatment. Additionally, it summarizes findings from various studies on the use of different types of nanofiber scaffolds for diabetic wounds and reviews methods of drug loading onto nanofiber scaffolds. These advancements broaden the horizon for effectively treating diabetic wounds.

Wound healing is a complex biological process with four main phases: hemostasis, inflammation, proliferation, and remodeling. Current treatments such as cotton and gauze may delay the wound healing process which gives a demand for more innovative treatments. Nanofibers are nanoparticles that resemble the extracellular matrix of the skin and have a large specific surface area, high porosity, good mechanical properties, controllable morphology, and size. Nanofibers are generated by electrospinning method that utilizes high electric force. Electrospinning device composed of high voltage power source, syringe that contains polymer solution, needle, and collector to collect nanofibers. Many polymers can be used in nanofiber that can be from natural or from synthetic origin. As such, electrospun nanofibers are potential scaffolds for wound healing applications. This review discusses the advanced electrospun nanofiber morphologies used in wound healing that is prepared by modified electrospinning techniques.

Oxidant environment and inflammation are the leading cause of chronic wounds such as diabetic ulcers. A dressing containing antioxidants would ensure accelerated wound healing. In this study, electrospun gold nanoparticle (GNP)-embedded nanofibers were developed. GNPs (about 7 nm) were synthesized using saffron extract as a reducing and capping agent (GNP-EXT). For comparison, nanoparticles of the same size were also synthesized using citrate (GNP-CIT). Nanoparticle colloids showed a zeta potential of -27 mV. FTIR confirmed the presence of the extract molecules on the nanoparticles. DPPH assay demonstrated the significant radical scavenging properties of the GNP-EXT. The effect of nanoparticles on the viability of NIH3T3 mouse fibroblast cells was evaluated with an MTT assay that showed no significant toxicity of nanoparticles even in the highest concentration of 250 ppm. Then poly (ɛ-caprolactone) (PCL)- Collagen nanofibers containing GNPs were electrospun. By using SEM, TEM, ATR-FTIR, and contact angle measurement, the nanofibers were characterized. Proper cell adhesion and spreading was observed on nanofibers by SEM and Alamar blue assay illustrated appropriate cyto-compatibility on the obtained nanofibers after 5 days of cell seeding. Wound healing assay also confirmed the cell supporting properties and biocompatibility. The results suggest that saffron-synthesized GNP-loaded nanofibers would be considered as potential wound dressings.

Herbal extracts have been used in traditional remedies since the earliest myths. They have excellent antimicrobial, anti-inflammatory, and antioxidant activities owing to various bioactive components in their structure. However, due to their inability to reach a target and low biostability, their use with a delivery vehicle has come into prominence. For this purpose, electrospun nanofibrous scaffolds have been widely preferred for the delivery and release of antimicrobial herbal extracts due to the flexibility and operational versatility of the electrospinning technique. Herein, we briefly reviewed the electrospun nanofibrous scaffolds as delivery systems for herbal extracts with a particular focus on the preclinical studies for wound-healing applications that have been published in the last five years. We also discussed the indirect effects of herbal extracts on wound healing by altering the characteristics of electrospun mats.

Diabetic ulcers are the second largest complication caused by diabetes mellitus. A great number of factors, including hyperchromic inflammation, susceptible microbial infection, inferior vascularization, the large accumulation of free radicals, and other poor healing-promoting microenvironments hold back the healing process of chronic diabetic ulcer in clinics. With the increasing clinical cases of diabetic ulcers worldwide, the design and development of advanced wound dressings are urgently required to accelerate the treatment of skin wounds caused by diabetic complications. Electrospinning technology has been recognized as a simple, versatile, and cost-reasonable strategy to fabricate dressing materials composed of nanofibers, which possess excellent extracellular matrix (ECM)-mimicking morphology, structure, and biological functions. The electrospinning-based nanofibrous dressings have been widely demonstrated to promote the adhesion, migration, and proliferation of dermal fibroblasts, and further accelerate the wound healing process compared with some other dressing types like traditional cotton gauze and medical sponges, etc. Moreover, the electrospun nanofibers are commonly harvested in the structure of nonwoven-like mats, which possess small pore sizes but high porosity, resulting in great microbial barrier performance as well as excellent moisture and air permeable properties. They also serve as good carriers to load various bioactive agents and/or even living cells, which further impart the electrospinning-based dressings with predetermined biological functions and even multiple functions to significantly improve the healing outcomes of different chronic skin wounds while dramatically shortening the treatment procedure. All these outstanding characteristics have made electrospun nanofibrous dressings one of the most promising dressing candidates for the treatment of chronic diabetic ulcers. This review starts with a brief introduction to diabetic ulcer and the electrospinning process, and then provides a detailed introduction to recent advances in electrospinning-based strategies for the treatment of diabetic wounds. Importantly, the synergetic application of combining electrospinning with bioactive ingredients and/or cell therapy was highlighted. The review also discussed the advantages of hydrogel dressings by using electrospun nanofibers. At the end of the review, the challenge and prospects of electrospinning-based strategies for the treatment of diabetic wounds are discussed in depth.

Diabetic foot ulcer (DFU) is a serious health issue of diabetes mellitus that affects innumerable people worldwide. Management and treatment of this complication are challenging, especially for those whose immune system is weak.

To discuss the plants and their parts used to heal DFU, along with the mode of their administration in diabetic patients.

The original articles on "the plants for the treatment of DFU" studied in clinical cases only were obtained from various bibliographic databases using different keywords.

The search resulted in 22 clinical cases records with 20 medicinal plants belonging to 17 families on 1553 subjects. The fruits and leaves were the most preferentially used parts for DFU treatment, regardless of whether they were being administered orally or applied topically. Of the 20 medicinal plants, 19 reported their effectiveness in increasing angiogenesis, epithelialization, and granulation, thus hastening the wound-healing process. The efficacy of these botanicals might be attributed to their major bioactive compounds, such as actinidin and ascorbic acid (in Actinidia deliciosa), 7-O-(β-D-glucopyranosyl)-galactin (in Ageratina pichinchensis), omega-3-fatty acid (in Linum usitatissimum), isoquercetin (in Melilotus officinalis), anthocyanins (in Myrtus communis), and plantamajoside (in Plantago major).

The validation of mechanisms of action underlying these phytocompounds contributing to the management of DFU can aid in our better understanding of creating efficient treatment options for DFU and its associated problems.

Biomaterial-based therapies have been receiving attention for treating microbial infections mainly to overcome the increasing number of drug-resistant bacterial strains and off-target impacts of therapeutic agents by conventional strategies. A fibrous, non-soluble protein, collagen, is one of the most studied biopolymers for the development of antimicrobial biomaterials owing to its superior physicochemical, biomechanical, and biological properties. In this study, we reviewed the different approaches used to develop collagen-based antimicrobial devices, such as non-pharmacological, antibiotic, metal oxide, antimicrobial peptide, herbal extract-based, and combination approaches, with a particular focus on preclinical studies that have been published in the last decade.

Diabetic foot ulcers (DFUs) are one of the main complications of diabetes and are characterized by their complexity and severity, which are frequently aggravated by overexpressed inflammatory factors and polymicrobial infections. Most dressing systems offer a passive action in the treatment of DFUs, being frequently combined with antibiotic or immunomodulatory therapies. However, in many instances due to these combined therapies' inability to properly fight microbial presence, and provide a suitable, breathable and moist environment that is also capable of protecting the site from secondary microbial invasions or further harm, aggravation of the wound state is unavoidable and lower limb amputations are necessary. Considering these limitations and knowing of the urgent demand for new and more effective therapeutic systems for DFU care that will guarantee the quality of life for patients, research in this field has boomed in the last few years. In this review, the emerging innovations in DFU dressing systems via fiber-based scaffolds modified with bioactive compounds have been compiled; data focused on the innovations introduced in the last five years (2017-2022). A generalized overview of the classifications and constraints associated with DFUs healing and the bioactive agents, both antimicrobial and immunomodulatory, that can contribute actively to surpass such issues, has also been provided.

Chronic diabetic wounds are one of the main complications of diabetes, manifested by persistent inflammation, decreased epithelialization motility, and impaired wound healing. This will not only lead to the repeated hospitalization of patients, but also bear expensive hospitalization costs. In severe cases, it can lead to amputation, sepsis or death. Electrospun nanofibers membranes have the characteristics of high porosity, high specific surface area, and easy functionalization of structure, so they can be used as a safe and effective platform in the treatment of diabetic wounds and have great application potential. This article briefly reviewed the pathogenesis of chronic diabetic wounds and the types of dressings commonly used, and then reviewed the development of electrospinning technology in recent years and the advantages of electrospun nanofibers in the treatment of diabetic wounds. Finally, the reports of different types of nanofiber dressings on diabetic wounds are summarized, and the method of using multi-drug combination therapy in diabetic wounds is emphasized, which provides new ideas for the effective treatment of diabetic wounds.

Nanofibrous wound dressing is one of the most prominent stratagems for wound caring/management. This research is an approach for designing an electrospun wound dressing based on poly(ε-caprolactone)/hydroxypropyl cellulose/zinc oxide nanoparticles (PCL/HPC/n-ZnO), in which response surface methodology (RSM) was utilized to ascertain the optimum sample. It was observed that the addition of n-ZnO and Melilotus Officinalis (MO) extract could increase the fibers mean diameter, pore size, and crystallinity of mats. The mentioned quantities for a sample with the highest MO content (PHZM10) were equal to 469±105 nm, 544±370 nm, and 49.67%, respectively. Moreover, enhancing the amount of MO led to an increase in mechanical properties. In this respect, the PHZM10 sample had the modulus, strength, and toughness of 82.41±0.61, 20.45±0.30 MPa, and 4194.86 mJ, respectively. Also, according to the MTT assay, no cytotoxicity was reported from any of the manufactured samples. Besides, it was concluded that the antibacterial activity and nanofibrous structure of mats, and also their potential for release of MO extract could accelerate the wound healing. Hence, the wound closure index for the PHZM10 group was 99.3±1.1%. Based on all noted results, the PCL/HPC/n-ZnO/MO electrospun mats can be proposed as reassuring wound dressing candidates.

Multichannel structures in the design of nerve conduits offer potential advantages for regeneration of damaged nerves. However, lack of biochemical cues and electrical stimulation could hamper satisfactory nerve regeneration. The aim of this study was to simultaneously evaluate the effects of topographical, biological, and electrical cues on sciatic nerve regeneration. Accordingly, a series of multichannel nerve conduit was made using longitudinally-aligned laminin-coated poly (lactic-co-glycolic acid) (PLGA)/carbon nanotubes (CNT) nanofibers (NF, mean diameter: 455 ± 362 nm) in the lumen and randomly-oriented polycaprolactone (PCL) NF (mean diameter: 340 ± 200 nm) on the outer surface. In vitro studies revealed that the materials were nontoxic and able to promote cell attachment and proliferation on nanofibers and on fibrin gel. To determine the influence of laminin as biological and CNT as electrical cues on nerve regeneration, either of hollow PCL conduits, PLGA NF-embedded, PLGA/CNT NF-embedded or laminin-coated PLGA/CNT NF-embedded PCL conduits were implanted in rats. A new surgery method was utilized and results were compared with an autograft. The results of motor and sensory tests in addition to histopathological examination of the regenerated nerves demonstrated the formation of nerve fibers in laminin-coated PLGA/CNT NF-embedded PCL conduits. Results suggested that these conduits have the potential to improve sciatic nerve regeneration. Graphical abstract.