Wound Dressing Modifications for Accelerated Healing of Infected Wounds.

Infections that occur during wound healing involve the most frequent complications in the field of wound care which not only inhibit the whole process but also lead to non-healing wound formation. The diversity of the skin microbiota and the wound microenvironment can favor the occurrence of skin infections, contributing to an increased level of morbidity and even mortality. As a consequence, immediate effective treatment is required to prevent such pathological conditions. Antimicrobial agents loaded into wound dressings have turned out to be a great option to reduce wound colonization and improve the healing process. In this review paper, the influence of bacterial infections on the wound-healing phases and promising modifications of dressing materials for accelerated healing of infected wounds are discussed. The review paper mainly focuses on the novel findings on the use of antibiotics, nanoparticles, cationic organic agents, and plant-derived natural compounds (essential oils and their components, polyphenols, and curcumin) to develop antimicrobial wound dressings. The review article was prepared on the basis of scientific contributions retrieved from the PubMed database (supported with Google Scholar searching) over the last 5 years.

Passive Millimeter-Wave Imaging for Burns Diagnostics under Dressing Materials.

This paper presents a feasibility study of using a passive millimeter-wave imaging (PMMWI) system to assess burn wounds and the potential for monitoring the healing process under dressing materials, without their painful removal. Experimental images obtained from ex vivo porcine skin samples indicate that a ThruVision passive imager operating over the band 232-268 GHz can be used for diagnosing burns and for potentially monitoring the healing under dressing materials. Experimental images show that single and multiple burns are observed throughout dressing materials. As the interaction of millimeter-wave (MMW) radiation with the human body is almost exclusively with the skin, the major outcomes of the research are that PMMWI is capable of discriminating burn-damaged skin from unburned skin, and these measurements can be made through bandages without the imager making any physical contact with the skin or the bandage. This highlights the opportunity that the healing of burn wounds can be assessed and monitored without the removal of dressing materials. The key innovation in this work is in detecting single and multiple burns under dressing materials in noncontact with the skin and without exposing the skin to any type of manmade radiation (i.e., passive sensing technology). These images represent the first demonstration of burns wound under dressing materials using a passive sensing imager.

The Influence of Novel, Biocompatible, and Bioresorbable Poly(3-hydroxyoctanoate) Dressings on Wound Healing in Mice.

The human body's natural protective barrier, the skin, is exposed daily to minor or major mechanical trauma, which can compromise its integrity. Therefore, the search for new dressing materials that can offer new functionalisation is fully justified. In this work, the development of two new types of dressings based on poly(3-hydroxyoctanoate) (P(3HO)) is presented. One of the groups was supplemented with conjugates of an anti-inflammatory substance (diclofenac) that was covalently linked to oligomers of hydroxycarboxylic acids (Oli-dicP(3HO)). The novel dressings were prepared using the solvent casting/particulate leaching technique. To our knowledge, this is the first paper in which P(3HO)-based dressings were used in mice wound treatment. The results of our research confirm that dressings based on P(3HO) are safe, do not induce an inflammatory response, reduce the expression of pro-inflammatory cytokines, provide adequate wound moisture, support angiogenesis, and, thanks to their hydrophobic characteristics, provide an ideal protective barrier. Newly designed dressings containing Oli-dicP(3HO) can promote tissue regeneration by partially reducing the inflammation at the injury site. To conclude, the presented materials might be potential candidates as excellent dressings for wound treatment.

Synthetic Aperture Radar Imaging for Burn Wounds Diagnostics.

The need for technologies to monitor the wound healing under dressing materials has led us to investigate the feasibility of using microwave and millimetre wave radiations due to their sensitivity to water, non- ionising nature, and transparency to dressing materials and clothing. This paper presents synthetic aperture radar (SAR) images obtained from an active microwave and millimetre wave scanner operating over the band 15-40 GHz. Experimental images obtained from porcine skin samples with the presence of dressing materials and after the application of localised heat treatments reveal that SAR images can be used for diagnosing burns and for potentially monitoring the healing under dressing materials. The experimental images were extracted separately from the amplitude and phase measurements of the input reflection coefficient (S11). The acquired images indicate that skin and burns can be detected and observed through dressing materials as well as features of the skin such as edges, irregularities, bends, burns, and variation in the reflectance of the skin. These unique findings enable a microwave and millimetre-wave scanner to be used for evaluating the wound healing progress under dressing materials without their often-painful removal: a capability that will reduce the cost of healthcare, distress caused by long waiting hours, and the healthcare interventional time.

Assessment of Bandaged Burn Wounds Using Porcine Skin and Millimetric Radiometry.

This paper describes the experimental setup and measurements of the emissivity of porcine skin samples over the band of 80-100 GHz. Measurements were conducted on samples with and without dressing materials and before and after the application of localized heat treatments. Experimental measurements indicate that the differences in the mean emissivity values between unburned skin and burned damaged skin was up to ~0.28, with an experimental measurement uncertainty of ±0.005. Measured differences in the mean emissivity values between unburned and burn damaged skin increases with the depth of the burn, indicating a possible non-contact technique for assessing the degree of a burn. The mean emissivity of the dressed burned skin was found to be slightly higher than the undressed burned skin, typically ~0.01 to ~0.02 higher. This indicates that the signature of the burn caused by the application of localized heat treatments is observable through dressing materials. These findings reveal that radiometry, as a non-contact method, is capable of distinguishing between normal and burn-damaged skin under dressing materials without their often-painful removal. This indicates the potential of using millimeter wave (MMW) radiometry as a new type of medical diagnostic to monitor burn wounds.

Sustained release of herbal drugs using biodegradable scaffold for faster wound healing and better patient compliance.

Electrospun scaffold has been developed using biodegradable polymer and age old herbal drug for efficient wound healing patch with much better patient compliance. Positively charged smaller particle size (40 nm) of the drug has been prepared for greater penetration through epidermal barrier to enhance the wound healing activity of drug. Controlled drug release has been understood in terms of interactions between the components through spectroscopic techniques and calorimetric studies. In-vivo study using albino rats shows better wound healing efficiency of scaffold in terms of higher wound area contraction, minimum inflammation, faster epithelialization and vascularization. Cellular studies also endorse the scaffold as better biomaterial. Clinical studies also demonstrate fast healing of different type of wounds in presence of all three wound dressing materials with histological evidences. The complete biodegradation of the patch confirms its green nature of the developed patch.

Chitosan-Based Dressing Materials for Problematic Wound Management.

Wound healing is a complex mechanism involving a variety of factors and is a representative process of tissue growth and regeneration in our body. Surface-based interactions between the dressing material and the wound may significantly influence the healing phase. Advances in understanding the mechanism of wound healing have led to the development of numerous dressing materials that can accelerate the healing process. However, these materials have a passive role in wound healing. It is therefore necessary to develop novel wound dressing materials, especially effective for clinically problematic wounds. Chitosan-based dressing materials are considered suitable for clinically problematic wounds as they exhibit several characteristic features, such as facilitating hemostasis, enhanced wound healing during the inflammatory and proliferative phases, antimicrobial effect, etc. Here, we review the current status of clinically available dressing materials and studies on the biological characteristics of chitosan, and discuss the potential applications of chitosan in multi-functional dressing materials for accelarated wound healing.

Comparison of antimicrobial activity of selected, commercially available wound dressing materials.

OBJECTIVE: The aim of our study was to examine the antimicrobial potential of eight selected, commercially available wound dressings containing different antimicrobial agents: silver, chlorhexidine acetate, povidone-iodine, and manuka honey. METHOD: The materials were tested against four reference strains of bacteria: Staphylococcus aureus (PCM 2051), Staphylococcus epidermidis (PCM 2118), Pseudomonas aeruginosa (ATCC 27853), and Escherichia coli (K12), using the disc diffusion-like method and a time-killing assay. RESULTS: For both experiments, the highest activity against all four tested strains of bacteria was observed in the case of Mepilex Ag, which contains silver as an antibacterial agent. Incubation for four hours of a 10x10mm2 piece of this material in 10ml cells suspension (concentration: 109-1010CFU/ml) resulted in complete elimination of bacteria of all four strains tested. The same results were obtained for a povidone-iodine containing dressing, Inadine, though its activity was lower in the disc diffusion assay. Silvercel, Aquacel Ag and Melgisorb Ag, which also contain silver, also exhibited a satisfactory level of activity. In the case of Aquacel Ag, 24 hours' incubation resulted in complete elimination of the cells of both Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa.The Escherichia coli cells were killed after only four hours' treatment. High effectiveness against Escherichia coli was also demonstrated for Silvercel. However, 24 hours' includation was required for complete elimination of the cells of this bacteria strain. High activity against all tested bacteria, but only in the disc diffusion assay, was observed for Algivon, which contains manuka honey. The Medisorb Silver Pad, containing silver, and Bactigras, which contains chlorhexidine acetate, revealed much lower antimicrobial activity, particularly noticeable in the time-killing assay. In addition, we also tested the anti-staphylococcal activity of a biopolymer material impregnated with lysostaphin. Results revealed that its activity against Staphylococcus aureus was comparable to the most active wound dressings impregnated with silver or inadine. CONCLUSION: Some important differences in the antimicrobial potential of investigated materials have been found. The presented results could be of interest to clinicians managing wounds.

Timer switch to convert suction apparatus for negative pressure wound therapy application.

BACKGROUND: Negative pressure wound therapy (NPWT) is an established modality in the treatment of chronic wounds, open fractures, and post-operative wound problems. This method has not been widely used due to the high cost of equipment and consumables. This study demonstrates an indigenously developed apparatus which gives comparable results at a fraction of the cost. Readily available materials are used for the air-tight dressing. MATERIALS AND METHODS: Equipment consists of suction apparatus with adjustable pressure valve set to a pressure 125-150 mmHg. An electronic timer switch with a sequential working time of 5 min and a standby time of 3 min provides the required intermittent negative pressure. Readily available materials such as polyvinyl alcohol sponge, suction drains and steridrapes were used to provide an air tight wound cover. RESULTS: A total of 90 cases underwent 262 NPWT applications from 2009 to 2014. This series, comprised of 30 open fractures, 21 post-operative and 39 chronic wounds. The wound healing rate in our study was comparable to other published studies using NPWT. CONCLUSION: The addition of electronic timer switch will convert a suction apparatus into NPWT machine, and the results are equally effective compared to more expensive counter parts. The use of indigenous dressing materials reduces the cost significantly.

Photo-Responsive Hydrogel for Contactless Dressing Change to Attenuate Secondary Damage and Promote Diabetic Wound Healing.

Dressing change is a significant and inevitable process during wound healing. Possible secondary damage caused through dressing removal may impose a great threat on wound recovery, thus resulting in healing delays and ultimately a higher cost of hospitalization. Hence, a non-contact refreshable dressing with an ease of operation is of great desire, especially for chronic wounds where a long-term and repeated dressing change would be performed. Herein, an all-light-operated hydrogel dressing that would achieve a fast and remote-controllable dressing change (30 s for gelation/4 min for dissolution upon light irradiation) for chronic wounds is presented. In a diabetic murine model, substantially improved wound healing within 2-3 weeks is observed due to attenuated secondary damage during repeated dressing changes. Moreover, a promising facilitation of the healing processes of epithelialization, collagen deposition, cell proliferation, and inflammatory regulation is also detected, representing a synergistic effect of the photo-responsive hydrogel dressing for therapeutic efficiency.

Herbal-Based Dressings in Wound Management.

Wound management is one of the major global challenges in recent times, and woundassociated infection has a significant impact on the healthcare economy worldwide. Wounds can be acute or chronic type, also diabetic, trauma, accidental, burn wounds and minor cuts, bruises, and rashes, etc. One of the primary treatment options available in these conditions are the use of suitable dressing materials to cover the wound and accelerate the healing process. Since ancient times, according to archaeological theories, medicinal plants and oils have been employed for the treatment of wounds. Today researchers across the globe are focusing their efforts on fabrication of novel dressing materials that can provide the most effective treatment, easy exchange of nutrients, and absorb exudate from the wounds. Very lately, various research groups are also concentrating on the design and development of herb-loaded wound dressings, as herbal preparations contain numerous phytoconstituents with a broad spectrum of pharmacological properties when compared to synthetic drugs and also due to the perceived notion that herbal products are generally safe, even when administered over prolonged periods. They contain numerous bioactive that can act on the various phases of the wound healing process, providing an ideal environment for the healing process. The present review discusses the numerous approaches that are employed for the preparation of dressing materials incorporated with plant-derived phytoconstituents/extracts. This review also provides an insight into the healing process and wound healing agents derived from medicinal plants and oils. The review can serve as a database for researchers working in this field and can help them to select the most appropriate dressing material for the effective delivery of herbal preparations in the management of wounds.

Recent Tissue Engineering Approaches to Mimicking the Extracellular Matrix Structure for Skin Regeneration.

Inducing tissue regeneration in many skin defects, such as large traumatic wounds, burns, other physicochemical wounds, bedsores, and chronic diabetic ulcers, has become an important clinical issue in recent years. Cultured cell sheets and scaffolds containing growth factors are already in use but have yet to restore normal skin tissue structure and function. Many tissue engineering materials that focus on the regeneration process of living tissues have been developed for the more versatile and rapid initiation of treatment. Since the discovery that cells recognize the chemical-physical properties of their surrounding environment, there has been a great deal of work on mimicking the composition of the extracellular matrix (ECM) and its three-dimensional network structure. Approaches have used ECM constituent proteins as well as morphological processing methods, such as fiber sheets, sponges, and meshes. This review summarizes material design strategies in tissue engineering fields, ranging from the morphology of existing dressings and ECM structures to cellular-level microstructure mimicry, and explores directions for future approaches to precision skin tissue regeneration.

Simple and Efficient Pressure Ulcer Reconstruction via Primary Closure Combined with Closed-Incision Negative Pressure Wound Therapy (CiNPWT)-Experience of a Single Surgeon.

BACKGROUND: In this study, we aimed to analyze the clinical efficacy of closed-incision negative pressure wound therapy (CiNPWT) when combined with primary closure (PC) in a patient with pressure ulcers, based on one single surgeon's experience at our medical center. METHODS: We retrospectively reviewed the data of patients with stage III or IV pressure ulcers who underwent reconstruction surgery. Patient characteristics, including age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, application of CiNPWT to reconstructed wounds, duration of hospital stay, and wound complications were analyzed. RESULTS: Operation time (38.16 ± 14.02 vs. 84.73 ± 48.55 min) and duration of hospitalization (36.78 ± 26.92 vs. 56.70 ± 58.43 days) were shorter in the PC + CiNPWT group than in the traditional group. The frequency of debridement (2.13 ± 0.98 vs. 2.76 ± 2.20 times) was also lower in the PC + CiNPWT group than in the traditional group. The average reconstructed wound size did not significantly differ between the groups (63.47 ± 42.70 vs. 62.85 ± 49.94 cm2), and there were no significant differences in wound healing (81.25% vs. 75.38%), minor complications (18.75% vs. 21.54%), major complications (0% vs. 3.85%), or mortality (6.25% vs. 10.00%) between the groups. CONCLUSIONS: Our findings indicate that PC combined with CiNPWT represents an alternative reconstruction option for patients with pressure ulcers, especially in those for whom prolonged anesthesia is unsuitable.

Silk sericin/fibroin electrospinning dressings: a method for preparing a dressing material with high moisture vapor transmission rate.

The current study focuses on the preparation of sericin and silk fibroin blend electrostatic spinning fiber film dressing. The surface morphology of the fiber films was observed by scanning electron microscope, and the hydrophilicity and swelling property of the fiber membrane dressing were analyzed. The biocompatibility of the four dressings was verified by the CCK-8 method and confocal laser microscopy. This experiment showed that the dressing group with the ratio of sericin to silk fibroin of 3:7 had better performance, offering fine and uniform fiber structure, good surface hydrophilicity, high water vapor transmission rate. The swelling rate of it was 822.77 ± 62.78%, and the tensile properties reached the requirements of dressing materials and had an excellent ability to promote cell adhesion and proliferation. This paper provides a possible method for producing of dressing materials with good hydrophilicity and high moisture vapor transmission rate.

Nanoparticle-driven self-assembling injectable hydrogels provide a multi-factorial approach for chronic wound treatment.

Chronic wounds represent a major health burden and drain on medical system. Efficient wound repair is only possible if the dressing materials target simultaneously multiple factors involved in wound chronicity, such as deleterious proteolytic and oxidative enzymes and high bacterial load. Here we develop multifunctional hydrogels for chronic wound management through self-assembling of thiolated hyaluronic acid (HA-SH) and bioactive silver-lignin nanoparticles (Ag@Lig NPs). Dynamic and reversible interactions between the polymer and Ag@Lig NPs yield hybrid nanocomposite hydrogels with shear-thinning and self-healing properties, coupled to zero-order kinetics release of antimicrobial silver in response to infection-related hyalurodinase. The hydrogels inhibit the major enzymes myeloperoxidase and matrix metalloproteinases responsible for wound chronicity in a patient's wound exudate. Furthermore, the lignin-capped AgNPs provide the hydrogel with antioxidant properties and strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The nanocomposite hydrogels are not toxic to human keratinocytes after 7 days of direct contact. Complete tissue remodeling and restoration of skin integrity is demonstrated in vivo in a diabetic mouse model. Hematological analysis reveals lack of wound inflammation due to bacterial infection or toxicity, confirming the potential of HA-SH/Ag@Lig NPs hydrogels for chronic wound management. STATEMENT OF SIGNIFICANCE: Multifunctional hydrogels are promising materials to promote healing of complex wounds. Herein, we report simple and versatile route to prepare biocompatible and multifunctional self-assembled hydrogels for efficient chronic wound treatment utilizing polymer-nanoparticle interactions. Hybrid silver-lignin nanoparticles (Ag@Lig NPs) played both: i) structural role, acting as crosslinking nodes in the hydrogel and endowing it with shear-thinning (ability to flow under applied shear stress) and self-healing properties, and ii) functional role, imparting strong antibacterial and antioxidant activity. Remarkably, the in situ self-assembling of thiolated hyaluronic acid and Ag@Lig NPs yields nanocomposite hydrogels able to simultaneously inhibits the major factors involved in wound chronicity, namely the overexpressed deleterious proteolytic and oxidative enzymes, and high bacterial load.

Emerging Role of Hydrogels in Drug Delivery Systems, Tissue Engineering and Wound Management.

The popularity of hydrogels as biomaterials lies in their tunable physical properties, ability to encapsulate small molecules and macromolecular drugs, water holding capacity, flexibility, and controllable degradability. Functionalization strategies to overcome the deficiencies of conventional hydrogels and expand the role of advanced hydrogels such as DNA hydrogels are extensively discussed in this review. Different types of cross-linking techniques, materials utilized, procedures, advantages, and disadvantages covering hydrogels are tabulated. The application of hydrogels, particularly in buccal, oral, vaginal, and transdermal drug delivery systems, are described. The review also focuses on composite hydrogels with enhanced properties that are being developed to meet the diverse demand of wound dressing materials. The unique advantages of hydrogel nanoparticles in targeted and intracellular delivery of various therapeutic agents are explained. Furthermore, different types of hydrogel-based materials utilized for tissue engineering applications and fabrication of contact lens are discussed. The article also provides an overview of selected examples of commercial products launched particularly in the area of oral and ocular drug delivery systems and wound dressing materials. Hydrogels can be prepared with a wide variety of properties, achieving biostable, bioresorbable, and biodegradable polymer matrices, whose mechanical properties and degree of swelling are tailored with a specific application. These unique features give them a promising future in the fields of drug delivery systems and applied biomedicine.

Potential Biomolecules and Current Treatment Technologies for Diabetic Foot Ulcer: An Overview.

BACKGROUND: Diabetic foot ulceration remains a major challenge and is one of the most expensive and leading causes of major and minor amputations among patients with diabetic foot ulcer. Hence the purpose of this review is to emphasize on potential molecular markers involved in diabetic foot ulcer physiology, the efficacy of different types of dressing materials, adjunct therapy and newer therapeutic approach like nanoparticles for the treatment of diabetic foot ulcer. METHODS: We conducted a systematic literature review search by using Pubmed and other web searches. The quality evidence of diabetic foot ulcer biomolecules and treatments was collected, summarized and compared with other studies. RESULTS: The present investigation suggested that impaired wound healing in diabetic patients is an influence of several factors. All the advanced therapies and foot ulcer dressing materials are not suitable for all types of diabetic foot ulcers, however more prospective follow ups and in vivo and in vitro studies are needed to draw certain conclusion. Several critical wound biomolecules have been identified and are in need to be investigated in diabetic foot ulcers. The application of biocompatible nanoparticles holds a promising approach for designing dressing materials for the treatment of diabetic foot ulcer. CONCLUSION: Understanding the cellular and molecular events and identifying the appropriate treatment strategies for different foot ulcer grades will reduce recurrence of foot ulcer and lower limb amputation.

The accelerating effect of chitosan-silica hybrid dressing materials on the early phase of wound healing.

Commercialized dressing materials with or without silver have played a passive role in early-phase wound healing, protecting the skin defects from infections, absorbing exudate, and preventing dehydration. Chitosan (CTS)-based sponges have been developed in pure or hybrid forms for accelerating wound healing, but their wound-healing capabilities have not been extensively compared with widely used commercial dressing materials, providing limited information in a practical aspect. In this study, we have developed CTS-silica (CTS-Si) hybrid sponges with water absorption, flexibility, and mechanical behavior similar to those of CTS sponges. In vitro and in vivo tests were performed to compare the CTS-Si sponges with three commercial dressing materials [gauze, polyurethane (PU), and silver-containing hydrofiber (HF-Ag)] in addition to CTS sponges. Both in vitro and in vivo tests showed that CTS-Si sponges promoted fibroblast proliferation, leading to accelerated collagen synthesis, whereas the CTS sponges did not exhibit significant differences in fibroblast proliferation and collagen synthesis from gauze, PU, and HF-Ag sponges. In case of CTS-Si, the inflammatory cells were actively recruited to the wound by the influence of the released silicon ions from CTS-Si sponges, which, in return, led to an enhanced secretion of growth factors, particularly TGF-ß during the early stage. The higher level of TGF-ß likely improved the proliferation of fibroblasts, and as a result, collagen synthesis by fibroblasts became remarkably productive, thereby increasing collagen density at the wound site. Therefore, the CTS-Si hybrid sponges have considerable potential as a wound-dressing material for accelerating wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1828-1839, 2017.

Novel cellulose based materials for safe and efficient wound treatment.

The present study aims at achieving effects of improved hydrophilicity and microorganism inhibition, which are rarely simultaneously present in wound dressings. Viscose fibers in their non-woven form were modified using two different pathways. Effects of a two-step procedure, i.e. alkaline or oxygen plasma treatment followed by the attachment of silver chloride nanoparticles were compared to a one-step procedure, i.e. ammonium plasma treatment, which results in both desired material characteristics simultaneously. The surface properties of untreated and differently modified cellulose samples were analyzed by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), in vitro silver release, and hydrophilicity measurements. The treatment effect on antimicrobial activity was determined by the AATCC 100-1999 standard test. In light of the introduced wound dressing preparation procedures and the desired wound dressing characteristics, the effectiveness of the used procedures was evaluated. Antimicrobial activity was proven against all Gram negative bacteria, while the Gram positive bacteria survive the as-prepared samples. Hydrophilicity was proven to be excellent using both preparation procedures. The mentioned results prove the potential of the used procedures and encourage future developments toward the clinical proof of concept.