Active Wound Dressings Research Articles

Development of bacterial cellulose/alginate/chitosan composites incorporating copper (II) sulfate as an antibacterial wound dressing

Bacterial cellulose (BC) is a biopolymer having unique physical and mechanical properties that widen its usefulness in a diverse range of applications. To be used as a wound dressing however, it lacks natural ability to fight against bacterial infection. To widen its usage as an active wound dressing, BC was incorporated with sodium alginate (AG), chitosan (CS), and copper sulfate (Cu), with an aim of imparting a microstatic or an antimicrobial activity. The structure and properties of the obtained BC/AG/CS-Cu composites were systematically studied. These properties include weight fraction, tensile strength, swelling ratio, and release characteristics of Cu. The obtained BC/AG/CS-Cu composites exhibited antibacterial properties against both gram-positive Methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative bacteria Escherichia coli (E.coli). Moreover, an indirect cytotoxicity test was used to evaluate whether the obtained composites were safe to use in contact with living cells L929 mouse fibroblasts and human dermal fibroblasts. All the results obtained in this work showed that the obtained composites were promising materials to be used as an antimicrobial wound dressing.

Thermo‐mechanical and adhesive properties of polymeric films based on ZnAl‐hydrotalcite composites for active wound dressings

Composite films based on sodium carboxymethyl cellulose (Na‐CMC) loaded with a ZnAl(OH)2CO3·yH2O hydrotalcite (ZnAl‐HTlc), were developed and characterized. The composites were mechanically more stable than the matrix alone: the noticeable enhancement of elastic modulus, creep resistance and failure properties, all proportional to the filler content, came at the expenses of a certain embrittlement. The filler tended to aggregate in the composites and the size of the aggregates increased with ZnAl‐HTlc amount. Contact angle measurements highlighted how ZnAl‐HTlc introduction in the polymeric matrix could strongly modify the wettability conditions of the films increasing their hydrophilicity. Bioadhesion tests showed that the adhesion behavior of the composites decreased as ZnAl‐HTlc amount increases, testifying the influence of the filler on the ability of the film to bind skin surface. Therefore, the developed films may find application as active wound dressings since ZnAl‐HTlc can be easily intercalated with an active pharmaceutical ingredient to be progressively released on the wound. POLYM. ENG. SCI., 59:E112–E119, 2019. © 2018 Society of Plastics Engineers

A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing.

Functional active wound dressings are expected to provide a moist wound environment, offer protection from secondary infections, remove wound exudate and accelerate tissue regeneration, as well as to improve the efficiency of wound healing. Chitosan-based hydrogels are considered as ideal materials for enhancing wound healing owing to their biodegradable, biocompatible, non-toxic, antimicrobial, biologically adhesive, biological activity and hemostatic effects. Chitosan-based hydrogels have been demonstrated to promote wound healing at different wound healing stages, and also can alleviate the factors against wound healing (such as excessive inflammatory and chronic wound infection). The unique biological properties of a chitosan-based hydrogel enable it to serve as both a wound dressing and as a drug delivery system (DDS) to deliver antibacterial agents, growth factors, stem cells and so on, which could further accelerate wound healing. For various kinds of wounds, chitosan-based hydrogels are able to promote the effectiveness of wound healing by modifying or combining with other polymers, and carrying different types of active substances. In this review, we will take a close look at the application of chitosan-based hydrogels in wound dressings and DDS to enhance wound healing.

Risk Factors for Infection with Pseudomonas aeruginosa in Diabetic Foot Infections.

Selecting empirical therapy for a diabetic foot infection (DFI) requires knowing how likely infection with Pseudomonas aeruginosa is in a particular patient. We designed this study to define the risk factors associated with P aeruginosa in DFI. We performed a preplanned microbiological subanalysis of data from a study assessing the effects of treatment with intralesional epidermal growth factor for diabetic foot wounds in patients in Turkey between January 1, 2012, and December 31, 2013. Patients were screened for risk factors, and the data of enrolled individuals were recorded in custom-designed patient data forms. Factors affecting P aeruginosa isolation were evaluated by univariate and multivariate logistic regression analyses, with statistical significance set at P < .05. There were 174 patients enrolled in the main study. Statistical analysis was performed in 90 evaluable patients for whom we had microbiological assessments. Cultures were sterile in 19 patients, and 89 bacterial isolates were found in the other 71. The most frequently isolated bacteria were P aeruginosa (n = 23, 25.8%) and Staphylococcus aureus (n = 12, 13.5%). Previous lower-extremity amputation and a history of using active wound dressings were the only statistically significant independent risk factors for the isolation of P aeruginosa in these DFIs. This retrospective study provides some information on risk factors for infection with this difficult pathogen in patients with DFI. We need prospective studies in various parts of the world to better define this issue.

Designing and fabrication of curcumin loaded PCL/PVA multi-layer nanofibrous electrospun structures as active wound dressing

Active wound dressings play a significant role in burn and chronic wound treatment. In this study, electrospinning process is used to fabricate a novel three-layer active wound dressing based on ε-polycaprolactone (PCL), polyvinylalcohol (PVA), and curcumin (CU) as a biologically active compound. The main purpose for developing such a system is to control wound exudates, which remains a challenge, as well as enjoying the anti-bacterial property. Electrospinning process parameters are optimized by response surface methodology to achieve appropriate nanofibrous electrospun mats, and then, a three-layer dressing has been designed in view of water absorbability, anti-bacterial, and biocompatibility characteristics of the final dressing. The results illustrate that a three-layer dressing based on PCL/curcumin containing PVA as a middle layer with optimized thickness which is placed over the incision, absorbs three times exudates in comparison with pristine dressing. Anti-bacterial tests reveal that the dressing containing 16% curcumin exhibits anti-bacterial activity without sacrificing the acceptable level of cell viability.

Selected physical medicine interventions in the treatment of diabetic foot syndrome

The diabetic foot syndrome (DFS) is among chronic complications of diabetes mellitus; it can affect individuals with both type 1 and type 2 diabetes. Diabetic patients have up to a 25% lifetime risk of developing DFS, which is both a medical and social problem. Several studies have indicated that, apart from pharmacotherapy and modern active wound dressings, physical medicine also has a role in prevention and management of diabetic foot ulcers. The paper presents physical medicine interventions most recognized in the conservative management of DFS.

Physicochemical characteristics of chitosan/Beetosan hydrogels modified with Aloe vera

Event Abstract Back to Event Physicochemical characteristics of chitosan/Beetosan hydrogels modified with Aloe vera Bożena Tyliszczak1, Katarzyna Bialik-Wąs1, Dorota Walczyk1, Sonia Kudłacik1, Anna Drabczyk1 and Agnieszka Sobczak-Kupiec2 1 Department of Chemistry and Technology of Polymers, Cracow University of Technology, Poland 2 Institute of Inorganic Chemistry and Technology, Cracow University of Technology, Poland Chitin is the second most abundant polysaccharide, next to cellulose. Currently, chitin is isolated mainly from main source marine invertebrates like crab, krill, shrimp, lobster and fungi. Alternatively, chitosan can be extracted from naturally died honeybees after wintering. Innovativeness of performed synthesis of active hydrogel matrices was application of beetosan derived from multistage purification of naturally died honeybees. Structure of extracted beetosan was evaluated by means of FT-IR (see Figure 1) and XRD diffractometry (Figure 2). Figure 1. FT-IR spectra of Beetosan and commercial chitosan. Fig. 2 XRD diffractograms of Beetosan and commercial chitosan. Synthesis of chitosan based hydrogels was performed applying UV light, PEGDA (700) as cross linking agent and 2-hydroxy-2-methylpropiophenone as photoinitiator. Prior to exposure to UV light, the mixtures of chitosan and beetosan were modified with addition of Aloe vera juice (5-35% wt), which allowed to receive hydrogel materials with enhanced therapeutic activity. Interestingly, Aloe vera juice is commonly determined as "natural therapeutics" and possesses wide spectrum of biomedical applications. Due to the presence of variable active substances with significant pharmacological activity, Aloe vera juice possesses valuable antibacterial, antioxidant, antifungal, antiseptic, antiviral and immunological properties. Moreover, due to antibacterial and antiseptic activity and ability to simulate growth of fibroblasts, Aloe vera juice constitutes an promising component of hydrogel matrices that can be applied to form active wound dressings[1]-[3]. The received hydrogel matrices that contain the Aloe vera juice were physicochemically analyzed by means of FT-IR. The influence of added Aloe vera juice on the three dimensional structure and surface morphology of received hydrogels was evaluated applying SEM. In addition, the swelling degree in water and solutions of salts with variable pH and the incubation studies in both distilled water and simulated body fluids were evaluated. In addition, the release of active substances form hydrogel matrix was performed in phosphate buffer saline at pH equal 7.4 and 4.0. The authors would like to thank the The National Centre for Research and Development (Grant no: LIDER/033/697/L-5/13/NCBR/2014) for providing financial support to this project

Combined nitric oxide-releasing poly(vinyl alcohol) film/F127 hydrogel for accelerating wound healing

Nitric oxide (NO) releasing biomaterials represent a potential strategy for use as active wound dressings capable of accelerating wound healing. Topical NO-releasing poly(vinyl alcohol) (PVA) films and Pluronic F127 hydrogels (F127) have already exhibited effective skin vasodilation and wound healing actions. In this study, we functionalized PVA films with SNO groups via esterification with a mixture of mercaptosucinic acid (MSA) and thiolactic acid (TLA) followed by S-nitrosation of the SH moieties. These films were combined with an underlying layer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), i.e., PEO-PPO-PEO (Pluronic F127) hydrogel and used for the topical treatment of skin lesions in an animal model. The mixed esterification of PVA with MSA and TLA led to chemically crosslinked PVA-SNO films with a high swelling capacity capable of spontaneously releasing NO. Real time NO-release measurements revealed that the hydrogel layer reduces the initial NO burst from the PVA-SNO films. We demonstrate that the combination of PVA-SNO films with F127 hydrogel accelerates wound contraction, decreases wound gap and cellular density and accelerates the inflammatory phase of the lesion. These results were reflected in an increase in myofibroblastic differentiation and collagen type III expression in the cicatricial tissue. Therefore, PVA-SNO films combined with F127 hydrogel may represent a new approach for active wound dressings capable of accelerating wound healing.

Feasibility study of an active wound dressing based on hollow fiber membranes in a porcine wound model

InvestigationA novel active wound dressing (AWD) concept based on a microporous hollow fiber membrane network was investigated in an animal model. It provides a local solution-perfused environment for regenerative cell nutrition, wound irrigation, debris removal, electrolyte balancing, pH regulation, and topical antibiosis. The device is capable of supplying soluble factors, as tested experimentally for the recombinant human growth and differentiation factor-5 (rhGDF-5). MethodsFollowing in vitro studies for rhGDF-5 using primary human keratinocytes and dermal fibroblasts, we employed a porcine partial thickness wound model with five distinct wounds on each back of n=8 pigs. Four wound groups were perfused differently over 9 days and compared with a negative control wound without perfusion: (1) 1% trehalose solution, pH 5.5; (2) rhGDF-5 (150ng/ml) in 1% trehalose solution, pH 5.5; (3) nutrition solution; and (4) rhGDF-5 (150ng/ml) in nutrition solution with 1% trehalose, pH 5.5. ResultsPromoted wound healing was observed within group 1 and more pronounced within group 2. Groups 3 and 4, with nutrition solution, showed significant adverse effects on wound healing (p<0.05). ConclusionsThe investigated AWD concept appears to be an interesting therapeutic tool to study further wound healing support. Additionally, topical application of rhGDF-5 could be promising.

Active wound dressings based on bacterial nanocellulose as drug delivery system for octenidine.

Although bacterial nanocellulose (BNC) may serve as an ideal wound dressing, it exhibits no antibacterial properties by itself. Therefore, in the present study BNC was functionalized with the antiseptic drug octenidine. Drug loading and release, mechanical characteristics, biocompatibility, and antimicrobial efficacy were investigated. Octenidine release was based on diffusion and swelling according to the Ritger-Peppas equation and characterized by a time dependent biphasic release profile, with a rapid release in the first 8h, followed by a slower release rate up to 96 h. The comparison between lab-scale and up-scale BNC identified thickness, water content, and the surface area to volume ratio as parameters which have an impact on the control of the release characteristics. Compression and tensile strength remained unchanged upon incorporation of octenidine in BNC. In biological assays, drug-loaded BNC demonstrated high biocompatibility in human keratinocytes and antimicrobial activity against Staphylococcus aureus. In a long-term storage test, the octenidine loaded in BNC was found to be stable, releasable, and biologically active over a period of 6 months without changes. In conclusion, octenidine loaded BNC presents a ready-to-use wound dressing for the treatment of infected wounds that can be stored over 6 months without losing its antibacterial activity.

Collagen coated electrospun polycaprolactone (PCL) with titanium dioxide (TiO2) from an environmentally benign solvent: preliminary physico-chemical studies for skin substitute

Fabrication of nanofibers with some biomaterials based on natural materials (collagen) through electrospinning is an important area for research. The effect of collagen coating on polycaprolactone (PCL) nanofiber surfaces was studied here. In this work, PCL nanofibers with titanium dioxide (TiO2) nanopowder were used for the development of active wound dressings. We used glacial acetic acid as an environmentally benign solvent. The prepared nanofibers were coated with collagen by soaking the scaffold in 10 mg/mL and 20 mg/ml collagen solution overnight. The samples produced were subjected to contact angle measurements, SEM, FTIR, and XRD, and mechanical strength was determined. Nanofibers in the range of 200–800 nm were produced. The other study confirmed the physical interaction between collagen and PCL. The hydrophilicity of PCL nanofibers was increased; this was confirmed by observing contact angle values. A hydrophilic surface on the scaffold is necessary for biomedical applications. FTIR have proved the presence of an amide group on the PCL structure that facilitates cell adhesion and proliferation. SEM images have clearly proved the formation of nanofibers as well as the attachment of collagen to PCL nanofibers. XRD has shown the crystalline nature of the PCL polymer. PCL can impart more mechanical strength, although incorporation of collagen has decreased the tensile strength to some extent.

Morphology, drug release, antibacterial, cell proliferation, and histology studies of chamomile‐loaded wound dressing mats based on electrospun nanofibrous poly(ɛ‐caprolactone)/polystyrene blends

For the first time, it has been tried to achieve optimum conditions for electrospun poly(ε-caprolactone)/polystyrene (PCL/PS) nanofibrous samples as active wound dressings containing chamomile via D-optimal design approach. In this work, systematic in vitro and in vivo studies were carried out by drug release rate, antibacterial and antifungal evaluations, cell culture, and rat wound model along with histology observation. The optimized samples were prepared under the following electrospinning conditions: PCL/PS ratio (65/35), PCL concentration 9%(w/v), PS concentration 14%(w/v), distance between the syringe needle tip and the collector 15.5 cm, applied voltage 18 kV, and solution flow rate 0.46 mL h(-1) . The FE-SEM micrographs showed electrospun PCL/PS (65/35) nanofibrous sample containing 15% chamomile had a minimum average diameter (∼175 nm) compared to the neat samples (∼268 nm). The drug released resulted in a gradual and high amount of chamomile from the optimized PCL/PS nanofibrous sample (∼70%) in respect to PCL and PS nanofibers after 48 h. This claim was also confirmed by antibacterial and antifungal evaluations in which an inhibitory zone with a diameter of about 7.6 mm was formed. The rat wound model results also indicated that the samples loaded with 15% chamomile extract were remarkably capable to heal the wounds up to 99 ± 0.5% after 14 days post-treatment periods. The adhesion of mesenchymal stem cells and their viability on the optimized samples were confirmed by MTT analysis. Also, the electrospun nanofibrous mats based on PCL/PS (65/35) showed a high efficiency in the wound closure and healing process compared to the reference sample, PCL/PS nanofibers without chamomile. Finally, the histology analysis revealed that the formation of epithelial tissues, the lack of necrosis and collagen fibers accumulation in the dermis tissues for the above optimized samples.

Xanthan hydrogel films: Molecular conformation, charge density and protein carriers

In this article the molecular conformation of xanthan chains in hydrogel films was investigated by means of circular dichroism, showing substantial differences between xanthan hydrogel prepared in the absence (XNT) and in the presence of citric acid (XCA). The xanthan chains in XNT hydrogels films presented ordered conformation (helixes), while in XCA they were in the disordered conformation (coils), exposing a larger number of carboxylate groups than XNT. The large charge density in XCA hydrogels was evidenced by their behavior under variable ionic strength. Studies about the application of XNT and XCA for loading and delivering of bovine serum albumin (BSA) and lysozyme (LYZ) showed that both events are controlled by hydrogels and proteins net charge, which can be triggered by pH. The preservation of LYZ native conformation after hydrogel loading explained the substantial bactericidal activity of LYZ loaded hydrogels and enables their use as active wound dressings.

Amphiphilic Block Copolymer Vesicles for Active Wound Dressings: Synthesis of Model Systems and Studies of Encapsulation and Release

SummaryPolystyrene‐block‐poly(acrylic acid) (PS‐b‐PAA) diblock copolymers were synthesized via atom transfer radical polymerization (ATRP). Self‐assembly of these block copolymers into polymeric vesicles, so‐called polymersomes, was performed by addition of water to a solution of the block copolymers in tetrahydrofuran (THF). Various antimicrobial compounds and dyes were incorporated in the polymersomes and in addition to the corresponding size distributions, as determined by dynamic light scattering (DLS), the maximum attainable loading concentrations were determined. Using the release of incorporated calcein, which is a pH responsive dye, the principle of a light up probe approach for advanced in situ diagnostics was demonstrated. The release from PS‐b‐PAA vesicles via a vesicle‐to‐micelle transition was triggered by heating a vesicle suspension after addition of the plasticizer THF to 50 °C. Furthermore, a biocompatible and degradable block copolymer system, which contains degradable ester bonds in the main chain, was synthesized and investigated. In particular, poly(ethylene glycol)‐block‐polycaprolactone (PEG‐b‐PCL) copolymers were synthesized via ring‐opening polymerization (ROP). These copolymers were shown to form polymersomes as well and represent a promising family of degradable amphiphilic block copolymers for active wound dressings and related applications.

In vitro and in vivo evaluations of phenytoin sodium-loaded electrospun PVA, PCL, and their hybrid nanofibrous mats for use as active wound dressings

In this work, polyvinyl alcohol (PVA), poly(e-caprolactone) (PCL), and their electrospun PVA/PCL (80/20) hybrid nanofibrous mats were used for the development of active wound dressings. The biocompatibility and therapeutic effects of the developed products were studied by in vitro cell culture and in vivo experimental rat wound model. The release rate measurements by HPLC showed that the PVA nanofibrous sample containing phenytoin sodium (PHT-Na) has a higher level of the drug release compared to the hybrid PVA/PCL (80/20) and PCL nanofibrous mats. A mesenchymal stem cell was seeded on neat as well as drug-loaded PVA nanofibrous mats. The results represented that the mats provide a suitable environment for cell growth and viability. PVA nanofibers containing PHT-Na have a unique performance for fibroblasts and myofibroblasts cells formation and consequently reaching to the remodeling phase and faster healing of the wounds. Also, PHT-Na-loaded electrospun PVA nanofibrous mats showed a remarkable efficiency in wound closure compared with the treatments results from gauze, commercial wound dressing Comfeel®Plus, and 2 % PHT-Na ointment. Histology analysis showed the formation of epidermis, the lack of necrosis, and accumulation of collagen fibers in dermis for PVA nanofibrous mats containing PHT-Na.

Preparation and performance evaluation of tetracycline hydrochloride loaded wound dressing mats based on electrospun nanofibrous poly(lactic acid)/poly(ϵ‐caprolactone) blends

AbstractIn this article, we present the drug‐release rate, water uptake, water permeability, morphology, and mechanical properties of a series of active wound dressing nanofibrous mats prepared via an electrospinning process of poly(lactic acid) (PLA), poly(ϵ‐caprolactone) (PCL), and their (50/50) blends loaded with different doses of tetracycline hydrochloride antibiotic. The performance of these active wound dressings in terms of a sustained and suitable drug‐release rate, adequate water uptake and water permeability, and antibacterial activities were compared with those of a commercial wound dressing (Comfeel Plus). The results show that the dressings made from PCL and PLA/PCL blends showed better performance compared with the commercial wound dressing sample as far as these properties were concerned. The improved performance could be explained on the basis of the nanofibrous structure of the mats and the hydrophilicity of PCL and PLA. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Polymer–xerogel composites for controlled release wound dressings

Many polymers and composites have been used to prepare active wound dressings. These materials have typically exhibited potentially toxic burst release of the drugs within the first few hours followed by a much slower, potentially ineffective drug release rate thereafter. Many of these materials also degraded to produce inflammatory and cytotoxic products. To overcome these limitations, composite active wound dressings were prepared here from two fully biodegradable and tissue compatible components, silicon oxide sol–gel (xerogel) microparticles that were embedded in tyrosine-poly(ethylene glycol)-derived poly(ether carbonate) copolymer matrices. Sustained, controlled release of drugs from these composites was demonstrated in vitro using bupivacaine and mepivacaine, two water-soluble local anesthetics commonly used in clinical applications. By systematically varying independent compositional parameters of the composites, including the hydrophilic:hydrophobic balance of the tyrosine-derived monomers and poly(ethylene glycol) in the copolymers and the porosity, weight ratio and drug content of the xerogels, drug release kinetics approaching zero-order were obtained. Composites with xerogel mass fractions up to 75% and drug payloads as high as 13% by weight in the final material were fabricated without compromising the physical integrity or the controlled release kinetics. The copolymer–xerogel composites thus provided a unique solution for the sustained delivery of therapeutic agents from tissue compatible wound dressings.

A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages

AbstractWound dressings have experienced continuous and significant changes since the ancient times. The development starts with the use of natural materials to simply cover the wounds to the materials of the present time that could be specially made to exhibit various extraordinary functions. The modern bandage materials made of electrospun biopolymers contain various active compounds that are beneficial to the healing of wounds. These materials are fibrous in nature, with the size of fibers segments ranging from tens of nanometers to micrometers. With the right choices of biopolymers used for these fibrous materials, they could enhance the healing of wounds significantly compared with the conventional fibrous dressing materials, such as gauze. These bandages could be made such that they contain bioactive ingredients, such as antimicrobial, antibacterial, and anti‐inflammatory agents, which could be released to the wounds enhancing their healing. In an active wound dressing (AWD), the main purpose is to control the biochemical states of a wound in order to aid its healing process. This review provides an overview of different types of wounds, effective parameters in wound healing and different types of wound dressing materials with a special emphasis paid to those prepared by electrospinning. Copyright © 2009 John Wiley &amp; Sons, Ltd.

Characterization of anisotropic poly(vinyl alcohol) hydrogel by small- and ultra-small-angle neutron scattering

Poly(vinyl alcohol) (PVA) hydrogels are formed from PVA solution when physical cross-links form during freeze/thaw cycling. By applying a stress during the freeze/thaw process, PVA hydrogels with anisotropic mechanical properties are produced. We have used small- and ultra-small-angle neutron scattering to study the structure at length scales of 2 nm to 10 mum. By supplementing the neutron data with data from atomic force microscopy, we have probed a large range of length scales within which structural changes responsible for bulk anisotropy occur. We model the gel as interconnected PVA blobs of size 20-50 nm arranged in fractal aggregates extending to micrometers or tens of micrometers. Bulk mechanical anisotropy appears to be due to the alignment of blobs and connections between blobs. This information is essential for tailoring mechanical properties for applications where anisotropy is desirable such as to match the properties of natural tissue in coronary grafts and to control diffusive properties in active wound dressings.

Possibilities of molecular modeling of cellulose in fabrication of therapeutically active textile materials

Highly effective means of stopping capillary-parenchymatous bleeding — one of the main causes of death in people from 1 to 34 years of age in traffic accidents — were developed. Biologically active wound dressings that reduce purulent-necrotic wound cleansing time by 3 times, healing time by 2.5 times, and hospital stays by 6 times were developed.