An Inexpensive,Portable Device for Point‐of‐Need Generation of Silver‐Nanoparticle Doped Cellulose Acetate Nanofibers for Advanced Wound Dressing

This short communication describes the design and assembly of a new, miniaturized electrospinner to produce nanofibers at the site of need for drug delivery and wound dressing applications. The portable apparatus would eliminate the storage and transportation concerns with regards to the delicate nature of drug‐loaded nanofibers, thereby preserving product integrity at the site of use. Furthermore, the setup features a smaller size, a cheaper price, and components that are readily obtainable off‐the‐shelf, compared to those of available devices that are custom‐built and more expensive, making it desirable and accessible for other users in the field. As a proof‐of‐concept for wound care, the device is successfully used to electrospin three types of nanofibers comprised of pure cellulose acetate (CA), and CA respectively doped with 0.75 and 1.5 wt% silver nanoparticles. The miniaturized device is useful on account of the popularity of electrospinning as well as the potential to minimize wound infection due to the reduced manipulation of both the dressing and the wound from product generation to the point of need. Work is in progress to further develop the portable device and compare its product performance with traditional wound dressing materials for clinical translation.     

A Thermo‐ and Moisture‐Responsive Zwitterionic Shape Memory Polymer for Novel Self‐Healable Wound Dressing Applications

Developing wound dressings that have strong adhesion strength without causing any conglutination to the wound site is still challenging. Herein, is proposed that zwitterionic shape memory polymers can be applied as promising candidates for wound dressing. Sulfobetaine methacrylate (SBMA) is copolymerized with 2,3‐dihydroxypropyl methacrylate (DHMA) in the presence of boric acid as a cross‐linking agent. The prepared material exhibits multi‐stimuli responsive shape memory behaviors: it can rapidly return to its initial shape upon heating to 90 °C, and a gradual recovery is also observed by absorbing moisture in humid environments. The shape memory effect can be well adjusted via incorporation of sodium chloride to induce the dissociation of electrostatic interactions between PSBMA chains, leading to reduced transition temperature and faster shape recovery rate. Moreover, the dynamic nature of boron ester bonds and electrostatic interaction endows the material with effective and rapid self‐healing ability. It is also demonstrated that the deployment process of the dressing that a sample with an initially circular shape can perfectly fit and tightly bind to the wound site after moisture‐induced shape recovery. The proposed zwitterionic polymer can possibly extend the application scope of shape memory polymers and pave a new way for the design of wound dressings.     

Dual-Functional Nanofibrous Patches for Accelerating Wound Healing

Bacterial infections and inflammation are two main factors for delayed wound healing. Coaxial electrospinning nanofibrous patches, by co-loading and sequential co-delivering of anti-bacterial and anti-inflammation agents, are promising wound dressing for accelerating wound healing. Herein, curcumin (Cur) was loaded into the polycaprolactone (PCL) core, and broad-spectrum antibacterial tetracycline hydrochloride (TH) was loaded into gelatin (GEL) shell to prepare PCL-Cur/GEL-TH core-shell nanofiber membranes. The fibers showed a clear co-axial structure and good water absorption capacity, hydrophilicity and mechanical properties. In vitro drug release results showed sequential release of Cur and TH, in which the coaxial mat showed good antioxidant activity by DPPH test and excellent antibacterial activity was demonstrated by a disk diffusion method. The coaxial mats showed superior biocompatibility toward human immortalized keratinocytes. This study indicates a coaxial nanofiber membrane combining anti-bacterial and anti-inflammation agents has great potential as a wound dressing for promoting wound repair.     

In Situ Electrospinning Wound Healing Films Composed of Zein and Clove Essential Oil

Electrospun fibrous membranes have the potential to be effective wound dressings for promoting wound healing. However, the fabrication and application of the common electrospun fibrous wound dressings are usually complicated and separated. Here, electrospun zein/clove essential oil (CEO) fibrous membranes are fabricated and applied as a potential wound dressing through in situ electrospinning process by a portable electrospinning device. The in situ electrospinning process can directly electrospin zein/CEO membranes onto a wound site to cover the wound well and improve the convenience and comfort in use. The as‐spun zein/CEO membranes show a porous structure and exhibit higher gas permeability at 168.2 ± 43.3 mm s^?1, with superhydrophilicity to absorb the wound exudate and good biocompatibility as well as antibacterial effects to protect from infection. Moreover, the mice wound model study suggests that in situ electrospun zein/CEO promotes the wound healing process.     

Evaluation of Polymeric Matrix Loaded with Melatonin for Wound Dressing

The development of scaffolds mimicking the extracellular matrix containing bioactive substances has great potential in tissue engineering and wound healing applications. This study investigates melatonin—a methoxyindole present in almost all biological systems. Melatonin is a bioregulator in terms of its potential clinical importance for future therapies of cutaneous diseases. Mammalian skin is not only a prominent melatonin target, but also produces and rapidly metabolizes the multifunctional methoxyindole to biologically active metabolites. In our methodology, chitosan/collagen (CTS/Coll)-contained biomaterials are blended with melatonin at different doses to fabricate biomimetic hybrid scaffolds. We use rat tail tendon- and Salmo salar fish skin-derived collagens to assess biophysical and cellular properties by (i) Fourier transform infrared spectroscopy—attenuated total reflectance (FTIR–ATR), (ii) thermogravimetric analysis (TG), (iii) scanning electron microscope (SEM), and (iv) proliferation ratio of cutaneous cells in vitro. Our results indicate that melatonin itself does not negatively affect biophysical properties of melatonin-immobilized hybrid scaffolds, but it induces a pronounced elevation of cell viability within human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF), and reference melanoma cells. These results demonstrate that this indoleamine accelerates re-epithelialization. This delivery is a promising technique for additional explorations in future dermatotherapy and protective skin medicine.     

Development and Characterization of Gentamicin-Loaded Arabinoxylan-Sodium Alginate Films as Antibacterial Wound Dressing

Biopolymer-based antibacterial films are attractive materials for wound dressing application because they possess chemical, mechanical, exudate absorption, drug delivery, antibacterial, and biocompatible properties required to support wound healing. Herein, we fabricated and characterized films composed of arabinoxylan (AX) and sodium alginate (SA) loaded with gentamicin sulfate (GS) for application as a wound dressing. The FTIR, XRD, and thermal analyses show that AX, SA, and GS interacted through hydrogen bonding and were thermally stable. The AXSA film displays desirable wound dressing characteristics: transparency, uniform thickness, smooth surface morphology, tensile strength similar to human skin, mild water/exudate uptake capacity, water transmission rate suitable for wound dressing, and excellent cytocompatibility. In Franz diffusion release studies, >80% GS was released from AXSA films in two phases in 24 h following the Fickian diffusion mechanism. In disk diffusion assay, the AXSA films demonstrated excellent antibacterial effect against E.coli, S. aureus, and P. aeruginosa. Overall, the findings suggest that GS-loaded AXSA films hold potential for further development as antibacterial wound dressing material.     

Electrospun Nanofibers of Curdlan (β‐1,3 Glucan) Blend as a Potential Skin Scaffold Material

Curdlan (β‐1,3 glucan) (7 wt%) with polyvinyl alcohol (PVA) (10 wt%) is blended at 1:2 weight ratio and electrospun to get nanofibers and is crosslinked with glutaraldehyde vapor to make it insoluble in water. It has a fiber diameter of less than 100 nm and is hydrophilic (contact angle = 35°). It is biodegradable (10% in 14 d) and also has a good swelling behavior (≈170%). More than 100% of L6 cells are viable on this scaffold after 3 d. The scanning electron microscope images also reveal that cells are able to attach and spread in the nanofibrous scaffolds. In vitro scratch assay indicates that the wound closure rate of curdlan/PVA scaffold is better than PVA scaffold probably due to the immunomodulatory properties of the biopolymer. Thus our results indicate that curdlan/PVA scaffold can be an ideal material for wound healing applications.

     

Silver Loaded Nanofibrous Curdlan Mat for Diabetic Wound Healing: An In Vitro and In Vivo Study

A fibrous scaffold of curdlan/poly(vinyl alcohol) (PVA) blend is prepared by electrospinning technique and antimicrobial property is imparted to it by the addition of silver nitrate (1, 3, and 5 wt%). All the scaffolds except the PVA/curdlan with 5 wt% AgNO₃ show good viability of Swiss 3T3 fibroblast cells. Significant reductions in the growth of Staphylococcus aureus and Escherichia coli are also observed in all the scaffolds. In vitro scratch assay and cell adhesion studies indicate that the scaffold containing 1% AgNO₃ shows significant wound healing and better cell spreading. The in vivo results also show faster healing of excision wounds in diabetic rats treated with the same material when compared to the control and the commercial sample. Furthermore, downregulation of proinflammatory cytokines and upregulation of anti‐inflammatory cytokines on the skin of the treated animals confirm that PVA/curdlan/1% AgNO₃ electrospun mat could be a promising material for diabetic wound healing.     

Electrospinning of cellulose‐based nanofibers

Cellulose derivatives of carboxymethyl cellulose sodium salt (CMC), hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), and enzymatically treated cellulose have been electrospun, and the microstructure of the resulting nanofibers has been analyzed by scanning electron microscopy (SEM). Before electrospinning, the solutions were characterized by viscometry and surface tension measurements, and the results were correlated with spinnability. Four different CMC derivatives, varying in molecular weight (M_w), degree of substitution (DS), and substitution pattern, have been electrospun in mixtures with poly(ethylene oxide) (PEO), and nanofibers of various characteristics have formed. The CMC‐based nanostructures, i.e., the nonwoven sheet and individual nanofibers, proved to be independent of M_w and DS but largely dependent on the substitution pattern. The nonwoven sheets varied in homogeneity, and beads appeared on the individual fibers. Depending on the chemical nature of the CMC, the extraction of PEO resulted in pure CMC nanostructures of varying appearance, indicating that the distribution of PEO and CMC in the nanofibers also varied. Two different HPMC derivatives, varying in DS, were electrospun into nanofibers. Homogeneous nonwoven sheets based on nanofibers of similar appearance are formed, independent of the substitution content of the HPMC sample. Preliminary fibers were obtained from enzymatically treated cellulose in a solvent system based on lithium chloride dissolved in dimethyl acetamide (LiCl: DMAc). © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1473–1482, 2007     

Sustainable Approach to Superhydrophobic Surfaces Based on Water‐Born Electrospinning

Superhydrophobic surfaces are obtained by a sustainable approach by electrospinning of water‐based acrylate dispersion followed by mild silanization and removal of template polymer. The resulting nonwovens show very high superhydrophobicity and very low roll angle. In contrast to many other approaches, pores provide the required morphology to achieve superhydrophobicity. This new material provides a new approach to electrospun nonwoven coatings which can be of interest for textile applications.     

Multi‐Functional Polyurethane Hydrogel Foams with Tunable Mechanical Properties for Wound Dressing Applications

Polyurethane hydrogel foams synthesized through a facile one‐pot, solvent‐free process are described. The roles of polyethylene glycol (PEG) molecular weight, crosslinking density, and foam stabilizer concentration on polymer properties are evaluated for potential applications as wound dressing materials. Material characterization and wound dressing relevant performance evaluations are performed to understand effects of individual components and identify promising formulations. Surprisingly for a solvent‐free reaction, complete polymerization is confirmed by IR and gel fraction analyses. Foam stabilizing agent loading increases mechanical properties including Young's modulus, extensibility, and toughness while decreasing pore size and drug release rate. Mechanical properties are also dependent on the crystalline melting temperature of the PEG diol. Utilizing caffeine as a drug surrogate, high performance liquid chromatography (HPLC) drug‐release analysis identifies that polyurethane hydrogel foams exhibit initial burst release kinetics followed by sustained release over 24 h. Antibiotic compatibility and release is demonstrated for all formulations by zone of inhibition testing against gram‐positive and negative bacteria.

     

Electrospinning formaldehyde‐crosslinked zein solutions

In order to develop zein fibers with improved physical properties and solvent resistance, formaldehyde was used as a crosslinking reagent before spinning. The crosslinking reaction was carried out in either acetic acid or ethanolic HCl where the amount of crosslinking reagent was between 1 and 6%. Reactions were carried out at various times and temperatures. When carried out in acetic acid, the maximum amount of formaldehyde that could be used was 1.5% as gelation occurred at higher levels. In ethanolic HCl, 6% formaldehyde could be incorporated into zein. All solutions were successfully electrospun, producing predominantly ribbon and round fibers; the morphology was strongly dependent on solvent and spinning solids. The formaldehyde‐crosslinked zein fabrics had double the tensile strength of control fabrics. SDS‐PAGE analysis clearly showed crosslinking had occurred. Electrospun fabrics from all formaldehyde‐treated zein solutions required an additional heating step in order to be resistant to dissolution in acetic acid, a known very good solvent for zein. Copyright © 2011 Society of Chemical Industry     

Electrospinning of high‐molecule PEO solution

Electrospinning is a simple but powerful method for making nanofibers that can then be collected to create porous mats. We expand the range of this technique by making nanofibers from macromolecules with a molecular weight of 3,000,000, namely poly(ethylene oxide) (PEO). Gelation of PEO blocks its spinning by traditional electrospinning. PEO was mixed with pure alcohol, and in specific concentration 10 wt % and under vibration condition, the mixed solution behaves like polymers for electrospinning, the average diameter of the obtained nanofibers is about 100 nm. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3840–3843, 2007     

Electrospinning of Cellulose‐Based Fibers From NaOH/Urea Aqueous System

Cellulose‐based fibers were prepared by electrospinning from cellulose dissolved in NaOH/urea in the presence of a small amount of polyol binders. The as‐spun products were examined with SEM. Pure cellulose solution did not produce fibrous materials, because it often formed spherical nanoparticles with diameters ranging from 100 to 300 nm. However, bicomponent fibrous materials were obtained successfully from mixtures of cellulose and HMPEG or PVA by electrospinning. The cellulose/HMPEG electrospun fibers had average diameters of 400 nm. The content of NaOH and urea as well as the stiffness of cellulose chains were found to have significant effect on the electrospinning process.

     

Wound Healing Impairment in Type 2 Diabetes Model of Leptin-Deficient Mice—A Mechanistic Systematic Review

Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the world, associated with diabetic foot ulcers and impaired wound healing. There is an ongoing need for interventions effective in treating these two problems. Pre-clinical studies in this field rely on adequate animal models. However, producing such a model is near-impossible given the complex and multifactorial pathogenesis of T2DM. A leptin-deficient murine model was developed in 1959 and relies on either dysfunctional leptin (ob/ob) or a leptin receptor (db/db). Though monogenic, this model has been used in hundreds of studies, including diabetic wound healing research. In this study, we systematically summarize data from over one hundred studies, which described the mechanisms underlying wound healing impairment in this model. We briefly review the wound healing dynamics, growth factors’ dysregulation, angiogenesis, inflammation, the function of leptin and insulin, the role of advanced glycation end-products, extracellular matrix abnormalities, stem cells’ dysregulation, and the role of non-coding RNAs. Some studies investigated novel chronic diabetes wound models, based on a leptin-deficient murine model, which was also described. We also discussed the interventions studied in vivo, which passed into human clinical trials. It is our hope that this review will help plan future research.     

Preparation and Characterization of Polyvinyl Alcohol Based Copolymers as Wound Dressing Fibers

Biocompatible polyvinyl alcohol/polyethylene glycol and polyvinyl alcohol/polypropylene glycol copolymer mats were prepared by electrospinning. The composite fiber mats were subjected to detailed physical analysis complemented by scanning electron microscopy and Fourier transformations infrared spectroscopy. Scanning electron microscopy images showed that the morphology and diameters of the fibers were mainly affected by the types of polymers and their copolymer compositions. Microbial culture results showed that among the tested fibrous mats polyvinyl alcohol/50% polyethylene glycol gave the best results in preventing the cell attachment and proliferation. This novel electrospun matrix would be used as potential wound dressing material for skin regeneration.     

In Situ Viscosity‐Controlled Electrospinning with a Low Threshold Voltage

In the present study, a novel electrospinning method is proposed,where jet formation is aided by shearing the solution in situ. With a generalpolymer solution, viscosity decreases by shearing, that is, the solution isshear‐thinning. Poly(ethylene‐oxide) is used as a model polymer andthe effects of rotation speed, solution concentration, and gap size (the widthof the annular orifice) on the process and the morphology of the obtainedfibers are investigated. It is found that the threshold voltage for generatingmultiple jets decreased from 35 to 12 kV when rotation speed is higher than60 rpm (or shear rate more than 310 s^?1). Additionally, the results show thatfiber diameter increases as the concentration of the solution increases. Thechi‐square two‐sample test is used to compare the distribution of fibersproduced by the capillary method and the novel electrospinning process. Inthe authors' method, the viscosity of the solution can be changed by applyingmechanical forces on it during the electrospinning process, which results inthe initiation of the electrospinning jet at a low threshold voltage. It is alsofound that gap size has a similar effect on fiber diameter as needle diameter in classical electrospinning.     

The Gut-Skin Microbiota Axis and Its Role in Diabetic Wound Healing—A Review Based on Current Literature

Diabetic foot ulcers (DFU) are a growing concern worldwide as they pose complications in routine clinical practices such as diagnosis and management. Bacterial interactions on the skin surface are vital to the pathophysiology of DFU and may control delayed wound healing. The microbiota from our skin directly regulates cutaneous health and disease by interacting with the numerous cells involved in the wound healing mechanism. Commensal microbiota, in particular, interact with wound-repairing skin cells to enhance barrier regeneration. The observed microbes in DFU include Staphylococcus, Streptococcus, Corynebacterium, Pseudomonas, and several anaerobes. Skin commensal microbes, namely S. epidermidis, can regulate the gamma delta T cells and induce Perforin-2 expression. The increased expression of Perforin-2 by skin cells destroyed S. aureus within the cells, facilitating wound healing. Possible crosstalk between the human commensal microbiome and different cell types involved in cutaneous wound healing promotes the immune response and helps to maintain the barrier function in humans. Wound healing is a highly well-coordinated, complex mechanism; it can be devastating if interrupted. Skin microbiomes are being studied in relation to the gut-skin axis along with their effects on dermatologic conditions. The gut-skin axis illustrates the connection wherein the gut can impact skin health due to its immunological and metabolic properties. The precise mechanism underlying gut-skin microbial interactions is still unidentified, but the immune and endocrine systems are likely to be involved. Next-generation sequencing and the development of bioinformatics pipelines may considerably improve the understanding of the microbiome-skin axis involved in diabetic wound healing in a much more sophisticated way. We endeavor to shed light on the importance of these pathways in the pathomechanisms of the most prevalent inflammatory conditions including the diabetes wound healing, as well as how probiotics may intervene in the gut-skin axis.     

Electrospinning of plant oil‐based,non‐isocyanate polyurethanes for biomedical applications

Non‐isocyanate polyurethanes (NIPU) have rapidly emerged as a sustainable, less toxic, and environmentally friendly alternative to traditional isocyanate‐based thermoplastic polyurethane (TPU) synthesis. TPU is widely used in the medical industry due to its excellent mechanical properties and elasticity. However, little work has been done to synthesize and electrospin NIPU into fibrous mats for biomedical applications. In this work, melt polymerization of a plant oil‐based cyclic carbonate monomer with polyether soft segments and various diamines yielded isocyanate‐free, segmented poly(amide hydroxyurethane)s (PAHUs). Electrospinning of segmented PAHUs afforded ductile, free‐standing fibrous mats with Young's modulus values between 7 and 8 MPa, suitable for tissue scaffold applications. PAHU fiber mats exhibited 3–4 times greater water uptake than the electrospun TPU control, demonstrating potential utility in drug delivery. Fibroblasts adhered to electrospun PAHU fibrous mats with viability values over 90% after 72‐h, validating its biocompatibility. The results highlight the high performance and potential of electrospun isocyanate‐free polyurethanes mats for biomedical application. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46464.