Treatment Of Chronic Wounds Research Articles

Behaviour in Chronic Wounds of Vascular Origin

With an ageing population the number of people with chronic limb wounds of vascular origin is growing steadily. These wounds are managed conservatively, surgically and with hybrid approach. They have been treated by different specialists. The aim of the present study was to compare the results between the different methods of treatment – conservative, surgically and with hybrid approach, as well as to offer an approach to these wounds from vascular origin based on our experience in the clinic. For a period of 3 years 220 patients with venous wounds have been accepted in the department of vascular surgery in UHAT “St. Ekaterina”, Sofia. One hundred of them have been treated conservatively, the rest 120 – with complex approach – surgically, pharmaceutically, elastopia or with bandages. The rate of ageing ulcuses of venous origin did not differ significantly in 3 months in the two groups (55% to 66%), on account of recurrences at 12-month follow-up, which were significantly more common in the conservative therapy group (15% to 30%). We have followed-up the frequency of the healed wounds on the 1st, 3rd and 6th month. A significant difference in healing wounds of vascular origin with a complex approach (with open surgery and conservatively) even during the 1st month has been noticed. The complex approach applied as a treatment of chronic wounds with vascular origin is particularly important. The surgical or interventional correction of pathological changes of the vascular system are of great importance for the successful treatment of these ulcuses.

Nanosilver-Functionalized Hybrid Hydrogels of Carboxymethyl Cellulose/Poly(Vinyl Alcohol) with Antibacterial Activity for Prevention and Therapy of Infections of Diabetic Chronic Wounds.

Diabetic foot ulcers (DFUs) are considered one of the most severe chronic complications of diabetes and can lead to amputation in severe cases. In addition, bacterial infections in diabetic chronic wounds aggravate this scenario by threatening human health. Wound dressings made of polymer matrices with embedded metal nanoparticles can inhibit microorganism growth and promote wound healing, although the current clinical treatments for diabetic chronic wounds remain unsatisfactory. In this view, this research reports the synthesis and characterization of innovative hybrid hydrogels made of carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) chemically crosslinked by citric acid (CA) functionalized with silver nanoparticles (AgNPs) generated in situ using an eco-friendly aqueous process. The results assessed through comprehensive in vitro and in vivo assays demonstrated that these hybrid polymer hydrogels functionalized with AgNPs possess physicochemical properties, cytocompatibility, hemocompatibility, bioadhesion, antibacterial activity, and biocompatibility suitable for wound dressings to support chronic wound healing process as well as preventing and treating bacterial infections. Hence, it can be envisioned that, with further research and development, these polymer-based hybrid nanoplatforms hold great potential as an important tool for creating a new generation of smart dressings for treating chronic diabetic wounds and opportunistic bacterial infections.

Local personalised treatment of long-term non-healing wounds

Introduction. A significant number of nosologies can result in long-term non-healing wounds that mostly have similar principles of local treatment. However, positive clinical outcomes are not always obtained in the management of such wounds. The authors have developed a personalized technology for local treatment of chronic wounds depending on their etiology. Aim. Was to investigate the effectiveness of the proposed methods and personalized approaches for local treatment of long-term nonhealing wounds. Materials and methods. Innovative methods of cleaning and stimulating regeneration of non-healing wounds have been developed in the study; their effectiveness was tested in 3 blocks of the study. The first block of the study included patients with long-term non-healing wounds of venous etiology, the second and third blocks included patients with long-term non-healing arterial and neurotrophic wounds, respectively. Each block involved two series of tests studying the developed methods of cryodestruction and stimulation of regeneration, respectively. In the 1st block, the 3rd series of tests was additionally conducted; it included patients with wounds larger than 20 cm2 in size. Results. The developed methods of cryodestruction accelerate the course of phase I of the wound process by 12% in patients with longterm non-healing wounds of venous etiology, by 27% in patients with critical ischemia of the lower extremities, by 70% in patients with neurotrophic etiology (p ≥ 0.05). The use of the proposed methods of stimulating regeneration significantly reduced the average area of wounds in the study blocks. The main components of treatment stimulating regeneration in long-term non-healing wounds have been identified considering wound etiology. Conclusion. The use of the developed algorithm for local personalized treatment of long-term non-healing wounds considering underlying disorders contributes to an earlier cleaning of the wound surface, elimination of inflammation and an increased activity of regeneration processes when compared with conventional approaches.

A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox)is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

Metal-Organic Frameworks and Their Composites for Chronic Wound Healing: From Bench to Bedside.

Chronic wounds are characterized by delayed and dysregulated healing processes. As such, they have emerged as an increasingly significant threat. The associated morbidity and socioeconomic toll are clinically and financially challenging, necessitating novel approaches in the management of chronic wounds. Metal-organic frameworks (MOFs) are an innovative type of porous coordination polymers, with low toxicity and high eco-friendliness. Documented anti-bacterial effects and pro-angiogenic activity predestine these nanomaterials as promising systems for the treatment of chronic wounds. In this context, the therapeutic applicability and efficacy of MOFs remain to be elucidated. It is, therefore, reviewed the structural-functional properties of MOFs and their composite materials and discusses how their multifunctionality and customizability can be leveraged as a clinical therapy for chronic wounds.

Digital Twin in Healthcare: A Study for Chronic Wound Management.

Although the concept of digital twin technology has been in existence for nearly half a century, its application in healthcare is a relatively recent development. In healthcare, the utilization of digital twin and data-driven models has proven to enhance clinical decision support, particularly in the treatment and assessment of chronic wounds, leading to improved clinical outcomes. This paper proposes the implementation of a digital twin in the domain of healthcare, specifically in the management of chronic wounds, by leveraging artificial intelligence techniques. The digital twin is composed of data collection, data processing, and AI models dedicated to wound healing. A novel AI pipeline is utilized to track the healing of chronic wounds. The digital twin, serving as a virtual representation of the actual wound, simulates and replicates the healing process. Furthermore, the proposed wound-healing prediction model effectively guides the treatment of chronic wounds. Additionally, by comparing the actual wound with its digital twin, the system enables early identification of non-healing wounds, facilitating timely adjustments and modifications to the treatment plan. By incorporating a digital twin in healthcare, the proposed system enables personalized and tailored treatments, potentially playing a crucial role in proactive problem identification.

Sprayable ciprofloxacin-loaded poloxamer hydrogels for wound infection treatment.

Topical antimicrobial treatments for severe burns and chronic wounds provide effective treatment against infections, but cause pain and discomfort with application. This study aimed to develop an antimicrobial topical formulation comprising thermoreversible poloxamers (Pluronic F127 and F68) and a broad-spectrum antimicrobial agent (ciprofloxacin hydrochloride, CH), that could be sprayed to eliminate application pain while maintaining antimicrobial activity. Formulations were characterized to determine their sprayability under cold conditions, gelation temperature, final storage modulus at skin temperature, drug release profile, ex vivo permeation through impaired porcine skin, and inhibition against common bacterial pathogens that colonize wounds. All cold formulations were sprayable from simple hand-held, pump-action sprayers due to their low viscosity. Upon heating, 17 and 20% Pluronic F127 formulations produced hydrogels eight to ten degrees below skin temperature, independent of ciprofloxacin loading. Increasing concentrations of Pluronic F127 increased the final storage modulus and viscosity of the gels, while inclusion of Pluronic F68 reduced these properties, showing that hydrogel rheological properties at skin temperature can be tuned via choice of formulation. Drug release was directly correlated to the rheological properties, with stiffer gels resulting in a decrease in drug release rate. Overall, gels released about 65-90% of their load within 12 hours. Ex vivo skin permeation demonstrated that drug was well retained in impaired porcine skin, which is desired to continuously treat bacteria localized to the wound. A well-diffusion assay indicated that the hydrogels had greater bacterial inhibition against Pseudomonas aeruginosa, Escherichia coli, and two strains of Staphylococcus aureus when compared to commercial controls. Overall, the results show the potential of CH-loaded poloxamer formulations as suitable sprayable topical dressings to deliver antimicrobials directly to wounds.

Metal-Phenolic Networks for Chronic Wounds Therapy.

Chronic wounds are recalcitrant complications of a variety of diseases, with pathologic features including bacterial infection, persistent inflammation, and proliferation of reactive oxygen species (ROS) levels in the wound microenvironment. Currently, the use of antimicrobial drugs, debridement, hyperbaric oxygen therapy, and other methods in clinical for chronic wound treatment is prone to problems such as bacterial resistance, wound expansion, and even exacerbation. In recent years, researchers have proposed many novel materials for the treatment of chronic wounds targeting the disease characteristics, among which metal-phenolic networks (MPNs) are supramolecular network structures that utilize multivalent metal ions and natural polyphenols complexed through ligand bonds. They have a flexible and versatile combination of structural forms and a variety of formations (nanoparticles, coatings, hydrogels, etc.) that can be constructed. Functionally, MPNs combine the chemocatalytic and bactericidal properties of metal ions as well as the anti-inflammatory and antioxidant properties of polyphenol compounds. Together with the excellent properties of rapid synthesis and negligible cytotoxicity, MPNs have attracted researchers' great attention in biomedical fields such as anti-tumor, anti-bacterial, and anti-inflammatory. This paper will focus on the composition of MPNs, the mechanisms of MPNs for the treatment of chronic wounds, and the application of MPNs in novel chronic wound therapies.

Evaluation of factors affecting the healing process of venous ulcers: A 12-week longitudinal study.

The process of healing venous ulcers is complex and influenced by many factors. By identifying the risk factors that influence a slower healing process, it is possible to predict impending delays and plan an individualised care plan. We analysed our database of patients with venous ulcers and identified clinical and demographic factors that delay the healing process. The research analysed the medical records of 754 patients with VLUs at Chronic Wound Treatment Unit of the University Hospital treated between 2001 and 2019. In study, the majority (64.3%) were women, the mean age was 65.7 years. The median duration of Chronic Venous Insufficiency was 24 years, 52% patients had had the disease >20 years, and 296 (39.3%) had experienced ulceration >12 months. Most of the patients (85.8%) had comorbidities, 84% were obese. At 12-week follow-up, 432 of the 754 ulcers had healed. Identified independent predictors of slower ulcer healing rates: wound area greater than 8.25 cm2 , location of the ulceration other than the medial ankle area, underlying disease >20 years, the presence of multiple comorbidities, depth of the ulcer, the presence of an unpleasant smell and alert pathogens. The presence of redness resulted in faster healing of VLUc. Many factors influence the healing process of venous ulceration. The results of the study can help in planning patient care and implementing appropriate early strategies to promote healing.

Antiseptic pyolytics and warming wet compresses improve the prospect of healing chronic wounds

Infection and suppuration of chronic wounds reduce the effectiveness of their treatment with a course of antibiotics and antiseptics combined with frequently renewed dressings. Therefore, daily short-term procedures of cleaning wounds from purulent-necrotic masses by mechanical methods, including the use of cleansing solutions and necrophage fly larvae, are also part of the general practice of chronic wound treatment. But even they do not always provide rapid healing of chronic wounds. In this connection, it is suggested to supplement the treatment of chronic wounds with preparations dissolving dense pus and wound dressings made in the form of warm moist compresses creating a local greenhouse effect in the wounds. Solutions of 3% hydrogen peroxide and 2–10% sodium bicarbonate heated to a temperature of 37°–45°С, possessing alkaline activity at рН 8.4–8.5 and enriched with dissolved carbon dioxide or oxygen gas (due to overpressure of 0.2 atm were suggested as pyolytic drugs. The first results of the use of pyolytics and warm moist dressings-compresses in the treatment of chronic wounds demonstrate a wound-healing effect. It is suggested to consider sanitizing therapy with pyolytics and warm moist wound dressings-compresses as an alternative to the use of modern cleansing solutions and artificial introduction of larvae of the necrophage fly into the purulent masses of chronic wounds to dissolve dense pus and accelerate the healing process.

Hydrogel Dressings: Multifunctional Solutions for Chronic Wound Healing; Focusing on In-Vivo Studies

Approximately, 1 to 2% of the population in developed countries suffer from chronic wounds. Nearly 6.5 million Americans have suffered at least one chronic wound. Chronic wound treatment is critical for patients to maintain their mental and physical well-being and improve their life quality. Chronic wounds can be treated in various ways, including hyperbaric oxygen therapy, debridement, ultrasound, skin grafts, negative pressure wound therapy, electromagnetic therapies, and hydrogel dressings. Hydrogels are among the most viable and promising options since their tunable characteristics, such as adhesiveness, antimicrobial and biodegradability, pre-angiogenic bioactivities, and anti-inflammatory, are beneficial to healing chronic wounds. In in vivo studies utilizing animal models, hydrogel dressings emerged as multifunctional solutions for chronic wound healing. These investigations consistently demonstrated that hydrogel dressings accelerated wound healing rates compared to traditional methods and maintained an optimal moist wound environment, which fostered tissue regeneration while minimizing scarring. Moreover, the remarkable biocompatibility of hydrogel dressings became evident in these animal model experiments, as they showed minimal adverse reactions in chronic wound patients. The results of these in vivo studies collectively highlight the promising potential of hydrogel dressings as a versatile therapeutic option for effectively managing chronic wounds. This review discusses dressings made of hydrogel in animal models for their multifunctional properties and potential benefits in treating chronic wounds. The efficacy of hydrogel dressings over other kinds of dressings is also demonstrated by providing examples of commercially available hydrogel dressings.

Adipose-derived Mesenchymal Stem Cells are Ideal for the Cell-based Treatment of Refractory Wounds: Strong Potential for Angiogenesis.

Although Mesenchymal Stem Cells (MSCs)-based therapy has been proposed as a promising strategy for the treatment of chronic lower-extremity ulcers, their optimal sources, amounts, and delivery methods are urgently needed to be determined. In this study, we compared the heterogeneity of the human MSCs derived from bone marrow (BMSCs), umbilical cord (UCMSCs), and adipose tissue (ADSCs) in accelerating wound healing and promoting angiogenesis and explored the underlying mechanism. Briefly, a diabetic rat model with a full-thickness cutaneous wound on the dorsal foot was developed. The wound was topically administered with three types of MSCs. Additionally, we carried out in vitro and in vivo analysis of the angiogenic properties of the MSCs. Moreover, the molecular mechanism of the heterogeneity of the MSCs derived from the three tissues was explored by transcriptome sequencing. When compared with the BMSCs- and UCMSCs-treated groups, the ADSCs-treated group exhibited markedly accelerated healing efficiency, characterized by increased wound closure rates, enhanced angiogenesis, and collagen deposition at the wound site. The three types of MSCs formed three-dimensional capillary-like structures and promoted angiogenesis in vitro and in vivo, with ADSCs exhibiting the highest capacity for tube formation and pro-angiogenesis. Furthermore, transcriptome sequencing revealed that ADSCs had higher expression levels of angiogenesis-associated genes. Our findings indicate that MSCs-based therapy accelerates the healing of ischemia- and diabetes-induced lower-extremity ulcers and that adipose tissue-derived MSCs might be ideal for therapeutic angiogenesis and treatment of chronic ischemic wounds.

Antimicrobial Activity of Silver Nanoparticles Stabilized by Liposoluble Extract of Artemisia terrae-albae

The global spread of multi-resistant pathogenic microorganisms has significantly complicated the treatment of chronic wounds. The development of novel drugs requires a substantial time investment. Hybrid materials such as nanoparticles stabilized by plant extracts are considered the best for creating efficient antiseptic substances. This paper is the first to discuss quantitative and qualitative analyses of the phytochemical constituents of the medicinal plant Artemisia terrae-albae, collected in Kazakhstan. The antimicrobial activity of the extracts, as well as of silver nanoparticles (AgNPs) stabilized by Artemisia terrae-albae extract, were evaluated. AgNPs were characterized by an average size of 82 nm or larger with a negative surface charge. TEM analysis of the obtained suspension showed a nonuniform structure of particles synthesized at a low concentration of ethyl acetate solvent in water. The SPR peak of AgNPs@Art aq. extract was detected at 420 nm, while any clear SPR peak was observed for AgNPs@Art ethylacetate extract. Diluted Artemisia terrae-albae extracts did not exhibit pronounced antimicrobial activity due to the poor solubility of compounds in water. Nevertheless, the AgNPs@Art aq. and AgNPs@Art EtAc. extracts possessed antimicrobial activity against the Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 6538, Escherichia coli (ATCC 8739), and Candida albicans ATCC 10231 strains.

The Preparation and Clinical Efficacy of Amnion-Derived Membranes: A Review.

Biological tissues from various anatomical sources have been utilized for tissue transplantation and have developed into an important source of extracellular scaffolding material for regenerative medicine applications. Tissue scaffolds ideally integrate with host tissue and provide a homeostatic environment for cellular infiltration, growth, differentiation, and tissue resolution. The human amniotic membrane is considered an important source of scaffolding material due to its 3D structural architecture and function and as a source of growth factors and cytokines. This tissue source has been widely studied and used in various areas of tissue repair including intraoral reconstruction, corneal repair, tendon repair, microvascular reconstruction, nerve procedures, burns, and chronic wound treatment. The production of amniotic membrane allografts has not been standardized, resulting in a wide array of amniotic membrane products, including single, dual, and tri-layered products, such as amnion, chorion, amnion-chorion, amnion-amnion, and amnion-chorion-amnion allografts. Since these allografts are not processed using the same methods, they do not necessarily produce the same clinical responses. The aim of this review is to highlight the properties of different human allograft membranes, present the different processing and preservation methods, and discuss their use in tissue engineering and regenerative applications.

Electrospun skin dressings for diabetic wound treatment: a systematic review.

Diabetes mellitus is a metabolic disease characterized by persistent hyperglycemia associated with a lack of insulin production or insulin resistance. In diabetic patients, the capacity for healing is generally decreased, leading to chronic wounds. One of the most common treatments for chronic wounds is skin dressings, which serve as protection from infection, reduce pain levels, and stimulate tissue healing. Furthermore, electrospinning is one of the most effective techniques used for manufacturing skin dressings. The purpose of this study was to perform a systematic review of the literature to examine the effects of electrospun skin dressings from different sources in the process of healing skin wounds using in vivo experiments in diabetic rats. The search was carried out according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Medical Subject Headings (MeSH) descriptors were defined as "wound dressing," "diabetes," "in vivo," and "electrospun." A total of 14 articles were retrieved from PubMed and Scopus databases. The results were based mainly on histological analysis and macroscopic evaluation, demonstrating moderate evidence synthesis for all experimental studies, showing a positive effect of electrospun skin dressings for diabetic wound treatment. This review confirms the significant benefits of using electrospun skin dressings for skin repair and regeneration. All the inks used were demonstrated to be suitable for dressing manufacturing. Moreover, in vivo findings showed full wound closure in most of the studies, with well-organized dermal and epidermal layers.

FastSkin® Concept: A Novel Treatment for Complex Acute and Chronic Wound Management.

Successful treatments for acute and chronic skin wounds remain challenging. The goal of this proof-of-concept study was to assess the technical feasibility and safety of a novel wound treatment solution, FastSkin®, in a pig model. FastSkin® was prepared from skin micrografts patterned in blood using acoustic waves. Upon coagulation, the graft was transferred on a silicone sheet and placed on wounds. Six full-thickness wounds were created at the back of two pigs and treated with either FastSkin®, split-thickness skin graft (positive control), a gauze coverage (negative control, NC1), or blood patterned without micrografts (negative control, NC2). Silicone sheets were removed after 7, 14, and 21 days. Wound healing was monitored for six weeks and evaluated macroscopically for re-epithelialization and morphometrically for residual wound area and wound contraction. Tissue regeneration was assessed with histology after six weeks. Re-epithelialization was faster in wounds covered with FastSkin® treatments compared to NC2 and in NC2 compared to NC1. Importantly, an enhanced collagen organization was observed in FastSkin® in contrast to NC treatments. In summary, two clinically approved skin wound treatments, namely micrografting and blood clot graft, were successfully merged with sound-induced patterning of micrografts to produce an autologous, simple, and biologically active wound treatment concept.

Wireless and Closed-Loop Smart Dressing for Exudate Management and On-Demand Treatment of Chronic Wounds.

Chronic wounds have become a significant threat to people's physical and mental health and have increased the burden of social medical care. Intelligent wound dressing (IWD) with wound condition monitoring and closed-loop on-demand drug therapy can shorten the healing process and alleviate patient suffering. However, single-function wound dressings cannot meet the current needs of chronic wound treatment. Here, a wearable IWD consisting of wound exudate management, sensor monitoring, closed-loop therapy, and flexible circuit modules is reported, which can achieve effective synergy between wound exudate management and on-demand wound therapy. The dressing is attached to the wound site, and the wound exudate is spontaneously pumped into the microfluidic channel for storage. Meanwhile, the IWD can detect the state of the wound through the temperature and humidity sensor, and use this as feedback to control the liquid metal (LM) heater through a smartphone, thereby realizing the on-demand drug release from the hydrogel. In a mouse model of infected wounds, IWD accelerates wound healing by reducing inflammatory responses, promoting angiogenesis and collagen deposition.

Sequential Anti-Infection and Proangiogenesis of DMOG@ZIF-8/Gelatin-PCL Electrospinning Dressing for Chronic Wound Healing.

Bacterial infection and insufficient neovascularization are two major obstacles to the healing of chronic wounds. Here, we present an antibacterial and proangiogenic dressing by encapsulating dimethyloxalylglycine (DMOG) in zeolitic imidazolate framework-8 (ZIF-8) and electrospinning it with gelatin-polycaprolactone (Gel-PCL). As Gel-PCL nanofibers degrade, ZIF-8 nanoparticles decompose, sequentially releasing bactericidal zinc ions and angiogenic DMOG molecules. This cascade process matches the wound-healing stages, ensuring suitable bioavailability and an effective duration of the active components while minimizing their side effects. In vitro, zinc ions released from the dressing (2.5% DMOG@ZIF-8) can eliminate over 90% of Escherichia coli and Staphylococcus aureus without compromising fibroblast cell proliferation and adhesion. In vivo, the dressing can heal skin wounds in Staphylococcus aureus-infected diabetic rats within 2 weeks, facilitated by the DMOG molecules discharged from ZIF-8 (loading rate 21.3%). Immunohistochemical analysis confirmed the regulated expression of factors by zinc ions and DMOG molecules. This work provides new insights into the design of multifunctional dressings for the treatment of chronic wounds.

Combining Alginate/PVPI-Based Film with Frequency Rhythmic Electrical Modulation System (FREMS) Technology as an Advanced Strategy for Diabetic Wounds.

Diabetes is rising as one of the most diffused diseases of the century with the related urgent necessity to face its systemic and local effects on the patients, such as cardiovascular problems, degeneration of limbs, and dysfunction of the wound healing process. The diffusion of leg ulcers has been estimated to be 1.51 for 1000 population, and these non-resolved wounds can produce several social, economic, and mental health issues in diabetic patients. At the same time, these people experience neuropathic pain that causes morbidity and a further decrease in their quality of life. Here, a new study is presented where asodium alginate/Polyvinylpyrrolidone-Iodine complex (PVPI)-based wound dressing is combined with the Frequency Rhythmic Electrical Modulation System (FREMS) technology, an established medical device for the treatment of neuropathic pain and diabetic ulcers. The produced Alginate/PVPI-based films are characterized in terms of morphology, chemistry, wettability, bio-/hemo-compatibility, and clotting capacity. Next, the Alginate/PVPI-based films are used together with FREMS technology in diabetic mice models, and synergism of their action in the wound closure rate and anti-inflammatory properties is found. Hence, how the combination of electrical neurostimulation devices and advanced wound dressings can be a new approach to improve chronic wound treatment is demonstrated.

Combinatorial wound dressings loaded with synergistic antibiotics in the treatment of chronic infected wounds

Advanced medicated wound dressings fabricated by electrospinning and electrospraying were prepared for the eradication of topical bacterial infections potentially applied in the management of infected acute and chronic non-healing wounds. Two different antibiotics (ciprofloxacin and rifampicin), with different aqueous solubilities and different mechanisms of antimicrobial action, were loaded within electrosprayed polymer microparticles and within electrospun nanofibers, respectively, to provide the resulting wound dressing with dually controlled antibiotic release kinetics. Due to the large surface area per volume ratio of the electrosprayed microparticles containing ciprofloxacin, an initial burst release was obtained. Simultaneously, the reduced surface area per volume ratio for the electrospun nanofibers together with the reduced aqueous solubility of rifampicin produced an extended rifampicin release over time. More importantly, a synergistic antimicrobial effect against Gram-positive and Gram-negative bacteria was observed when both antibiotics were combined. Biofilm formation prevention and the elimination of already formed mature bacterial biofilms were also successfully achieved using our advanced dressings. The lack of cytotoxicity of the advanced wound dressings here reported against eukaryotic cells at antimicrobial doses was also demonstrated using three different mammalian cell lines. Moreover, the advanced wound dressings successfully eliminated a Staphylococcus aureus mediated experimental infection in a chronic wound murine model showing their efficacy for the treatment of these complicated non-healing wounds. The strategy of advanced medicated wound dressings developed here may be used as a potential methodology for the fabrication of functional combinatorial materials that offer the ability to eradicate bacterial infections.