Site-Selective Photosynthesis of Ag-AgCl@Au Nanomushrooms for NIR-II Light-Driven O2- and O2•--Evolving Synergistic Photothermal Therapy against Deep Hypoxic Tumors.

Light-driven endogenous water oxidation has been considered as an attractive and desirable way to obtain O2 and reactive oxygen species (ROS) in the hypoxic tumor microenvironment. However, the use of a second near-infrared (NIR-II) light to achieve endogenous H2O oxidation to alleviate tumor hypoxia and realize deep hypoxic tumor phototherapy is still a challenge. Herein, novel plasmonic Ag-AgCl@Au core-shell nanomushrooms (NMs) were synthesized by the selective photodeposition of plasmonic Au at the bulge sites of the Ag-AgCl nanocubes (NCs) under visible light irradiation. Upon NIR-II light irradiation, the resulting Ag-AgCl@Au NMs could oxidize endogenous H2O to produce O2 to alleviate tumor hypoxia. Almost synchronously, O2 could react with electrons on the conduction band of the AgCl core to generate superoxide radicals (O2•-)for photodynamic therapy. Moreover, Ag-AgCl@Au NMs with an excellent photothermal performance could further promote the phototherapy effect. In vitro and in vivo experimental results show that the resulting Ag-AgCl@Au NMs could significantly improve tumor hypoxia and enhance phototherapy against a hypoxic tumor. The present study provides a new strategy to design H2O-activatable, O2- and ROS-evolving NIR II light-response nanoagents for the highly efficient and synergistic treatment of deep O2-deprived tumor tissue.

Ag2[Fe(CN)5NO]-Fabricated Hydrophobic Cotton as a Potential Wound Healing Dressing: An In Vivo Approach.

There have been reports of different types of wound dressings for various functions and purposes. Cotton being one of the most widely used wound dressing material due to its non-toxic, biodegradable, and other properties is used for fabrication as well as in the form of scaffolds for faster and effective wound closure. Our research team has already demonstrated the role of silver nitroprusside nanoparticles (SNPNPs) for wound healing and antibacterial activity. In the current study, we have developed cotton fabric impregnated with SNPNPs (SNPCFs) which remain photo inert and displayed long-term antimicrobial activity due to the surface modification with the silver nitroprusside complex. These SNPCFs were characterized by various analytical techniques (XRD, FTIR, UV spectroscopy, TGA, TEM, FESEM, EDAX, ICP-OES). The fabricated cotton dressings with nanoparticles showed an improved water contact angle (113-130°) than that of bare cotton gauze (60°) and exhibited more antibacterial property in case of both Gram-negative bacteria (Klebsiella aerogenes and Escherichia coli) and Gram-positive bacteria (Pseudomonas aeruginosa and Bacillus subtilis) even after several washings. The biocompatible nature of SNPCFs was assessed by in vivo chorioallantoic membrane assay that showed no obstruction in the formation of blood vessels. The SNPCFs exhibited better wound healing activity compared to the bare cotton and AgCFs as observed in the C57BL6/J mouse. The histopathological investigation reveals increase in re-epithelialization and deposition of connective tissue. The macrophage (M2) counts in SNPCF-treated skin tissues were supportive of more wound healing activity than mice treated with cotton fabric impregnated with chemically synthesized silver nanoparticles. Based on biodistribution analysis using ICP-OES, the data illustrated that a significant amount of silver is absorbed in the skin tissues of mice as compared to the blood and kidney. Furthermore, the absence of silver from the vital organs (heart, liver, and kidney) corroborates our hypothesis that the SNPCFs can act excellently in treating wounds when topically applied over skin. Thereafter, all these results highlight a strong possibility that SNPCFs exemplify the potential as a new antimicrobial and wound healing agent in future times.

AgBiS2 nanoparticles with synergistic photodynamic and bioimaging properties for enhanced malignant tumor phototherapy.

Bismuth (Bi)-based nanoagents for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) are attracting attention and are highly desired for malignant tumor diagnosis and treatment, but producing these materials is still a challenge. Here, we designed theranostic nanoparticles (NPs) based on AgBiS2 for computed tomography (CT) imaging and phototherapy of malignant tumors. These AgBiS2 NPs could effectively convert light into heat (with a high photothermal conversion efficiency of 36.51%) and significantly increase the generation of intracellular reactive oxygen species (ROS) under near infrared (NIR) laser irradiation. Remarkably, the combined PTT/PDT successfully inhibited the growth of a highly malignant osteosarcoma in vivo. In addition, AgBiS2 NPs exhibited an enhanced CT contrast ability for tumor imaging and killed clinically derived Staphylococcus aureus (S. aureus) to prevent infection. In conclusion the ability of AgBiS2 NPs to be used in phototherapy and CT imaging and their antibacterial abilities indicate that they are promising candidates for malignant tumor theranostics.

A Comprehensive Review of Topical Odor-Controlling Treatment Options for Chronic Wounds.

The process of wound healing is often accompanied by bacterial infection or critical colonization, resulting in protracted inflammation, delayed reepithelization, and production of pungent odors. The malodor produced by these wounds may lower health-related quality of life and produce psychological discomfort and social isolation. Current management focuses on reducing bacterial activity within the wound site and absorbing malodorous gases. For example, charcoal-based materials have been incorporated into dressing for direct adsorption of the responsible gases. In addition, multiple topical agents, including silver, iodine, honey, sugar, and essential oils, have been suggested for incorporation into dressings in an attempt to control the underlying bacterial infection. This review describes options for controlling malodor in chronic wounds, the benefits and drawbacks of each topical agent, and their mode of action. We also discuss the use of subjective odor evaluation techniques to assess the efficacy of odor-controlling therapies. The perspectives of employing novel biomaterials and technologies for wound odor management are also presented.

Silver-Collagen Dressing and High-voltage, Pulsed-current Therapy for the Treatment of Chronic Full-thickness Wounds: A Case Series.

Research suggests high-voltage, pulsed-current electric therapy (HVPC) is safe and effective for treating chronic wounds, and some data suggest silver- and collagen-based dressings may facilitate healing. A combination therapy utilizing both HVPC and silver-collagen dressing may present clinical advantages. To explore the effect of the combined therapy for chronic full-thickness wounds, a prospective, consecutive case series study was conducted. All participants were adults with wounds of at least 6 weeks' duration. After obtaining informed consent, patient and wound characteristics were obtained, wounds were assessed and measured, and patients received 2 to 3 HVPC treatments per week followed by application of the silver- and collagen-based dressing for a period of 2 weeks. Data were analyzed descriptively, and changes in wound size and volume from baseline were analyzed using Wilcoxon Signed Rank Test. The dressings were saturated with normal saline, used simultaneously during the 45-minute HVPC treatment, and left on top of the wound after treatment. The HVPC electro pads (stainless steel electrodes with a sponge interface) also were moistened with normal saline and the cathode placed on top of the wound. If the patient had more than 1 wound on the same leg, the anode was placed on the additional wound (otherwise over the intact skin nearby). Secondary dressings (eg, foam and/ or gauze) were used as clinically appropriate, and a 4-layer compression wrap was used, if indicated, for patients with venous ulcers. Ten (10) patients (3 women, 7 men, 57.30 ± 9.70 years old with 14 wounds of 273.10 ± 292.03 days' duration before study) completed the study and were included in the final analyses. Average wound surface area decreased from 13.78 ± 21.35 cm(2) to 9.07 ± 16.81 cm(2) (42.52% ± 34.16% decrease, P = 0.002) and wound volume decreased from 3.39 ± 4.31 cm(3) to 1.28 ± 2.25 cm(3) (66.84% ± 25.07% decrease, P = 0.001). One (1) patient was discharged with complete wound closure. No serious adverse events were noted, but a diagnosis of osteomyelitis in 1 patient and increased pain in a patient with significant Reynaud's syndrome suggest clinicians should be cautious using HVPC in these instances. The combined intervention utilizing both HVPC and silver-collagen dressing was effective in the treatment of chronic fullthickness wounds in this patient population. Controlled clinical studies of longer duration are needed to further explore the safety, effectiveness, and efficacy of this treatment.

A novel approach to antibiofilm susceptibility testing using a thermo-reversible matrix.

OBJECTIVE: Biofilm microorganisms are known to have a much higher tolerance to antimicrobials compared to their planktonic equivalents. Therefore, traditional antimicrobial susceptibility testing may not extrapolate to clinical treatment of infections of biofilm origin, and as a result, there is a need to not only develop antimicrobials with antibiofilm activity, but also suitable in vitro testing methods for their evaluation. In this study, we report on a novel method of antibiofilm testing using a thermo-reversible matrix (poloxamer 407), coupled with live/dead staining of bacteria cultured from the matrix. METHOD: Pseudomonas aeruginosa (NCIMB 8626) was cultured in medium containing poloxamer 407 at 37°C for 24 hours to generate biofilms. The preparation was cooled to liquefy the poloxamer and allow recovery of the biofilm cells, which were then stained with SYTO9 to determine viability following exposure to four antimicrobials: polyhexanide, octenadine dihydrochloride, povidone-iodine and silver carbonate. Over an 8-minute time period, fluorescence levels were spectrophotometrically measured and compared with bacterial controls, cultured in the absence of poloxamer and without antimicrobial. RESULTS: Untreated cells showed no reduction in viability over this period. Importantly, planktonic cells were more susceptible to test agents compared with those of a 'biofilm' phenotype cultured in poloxamer. Antibiofilm activity was evident for all of the test agents, with highest relative activity seen with octenadine dihydrochloride. CONCLUSION: In summary, a novel and relatively rapid approach to screen compounds for antibiofilm activity has been described. The method uses standard laboratory equipment and can be readily adapted to test a wide range of microorganisms and other antibiofilm compounds. DECLARATION OF INTEREST: This research was, in part, supported by Advanced Medical Solutions in the form of a Knowledge Transfer Project. Mr J. Nosworthy was employed by Advanced Medical Solutions. There are no other conflicts of interests to declare.

Combination of silver nanoparticles and Drosera binata extract as a possible alternative for antibiotic treatment of burn wound infections caused by resistant Staphylococcus aureus.

Staphylococcus aureus is the most common infectious agent involved in the development of skin infections that are associated with antibiotic resistance, such as burn wounds. As drug resistance is a growing problem it is essential to establish novel antimicrobials. Currently, antibiotic resistance in bacteria is successfully controlled by multi-drug therapies. Here we demonstrate that secondary metabolites present in the extract obtained from Drosera binata in vitro cultures are effective antibacterial agents against S. aureus grown in planktonic culture and in biofilm. Moreover, this is the first report demonstrating the synergistic interaction between the D. binata extract and silver nanoparticles (AgNPs), which results in the spectacular enhancement of the observed bactericidal activity, while having no cytotoxic effects on human keratinocytes. Simultaneous use of these two agents in significantly reduced quantities produces the same effect, i.e. by killing 99.9% of bacteria in inoculum or eradicating the staphylococcal biofilm, as higher amounts of the agents used individually. Our data indicates that combining AgNPs with either the D. binata extract or with its pure compound (3-chloroplumbagin) may provide a safe and highly effective alternative to commonly used antibiotics, which are ineffective towards the antibiotic-resistant S. aureus.

Extending the TIME concept: what have we learned in the past 10 years?(*).

The TIME acronym (tissue, infection/inflammation, moisture balance and edge of wound) was first developed more than 10 years ago, by an international group of wound healing experts, to provide a framework for a structured approach to wound bed preparation; a basis for optimising the management of open chronic wounds healing by secondary intention. However, it should be recognised that the TIME principles are only a part of the systematic and holistic evaluation of each patient at every wound assessment. This review, prepared by the International Wound Infection Institute, examines how new data and evidence generated in the intervening decade affects the original concepts of TIME, and how it is translated into current best practice. Four developments stand out: recognition of the importance of biofilms (and the need for a simple diagnostic), use of negative pressure wound therapy (NPWT), evolution of topical antiseptic therapy as dressings and for wound lavage (notably, silver and polyhexamethylene biguanide) and expanded insight of the role of molecular biological processes in chronic wounds (with emerging diagnostics and theranostics). Tissue: a major advance has been the recognition of the value of repetitive and maintenance debridement and wound cleansing, both in time-honoured and novel methods (notably using NPWT and hydrosurgery). Infection/inflammation: clinical recognition of infection (and non infective causes of persisting inflammation) is critical. The concept of a bacterial continuum through contamination, colonisation and infection is now widely accepted, together with the understanding of biofilm presence. There has been a return to topical antiseptics to control bioburden in wounds, emphasised by the awareness of increasing antibiotic resistance. Moisture: the relevance of excessive or insufficient wound exudate and its molecular components has led to the development and use of a wide range of dressings to regulate moisture balance, and to protect peri-wound skin, and optimise healing. Edge of wound: several treatment modalities are being investigated and introduced to improve epithelial advancement, which can be regarded as the clearest sign of wound healing. The TIME principle remains relevant 10 years on, with continuing important developments that incorporate new evidence for wound care.

Silver coated bioactive glass particles for wound healing applications.

Bioactive glass particles (0.42SiO(2)-0.15CaO-0.23Na(2)O-0.20ZnO) of varying size (<90 µm and 425-850 µm) were synthesized and coated with silver (Ag) to produce Ag coated particles (PAg). These were compared against the uncoated analogous particles (Pcon.). Surface area analysis determined that Ag coating of the glass particles resulted in increased the surface area from 2.90 to 9.12 m(2)/g (90 µm) and 1.09-7.71 m(2)/g (425-850 µm). Scanning electron microscopy determined that the Ag coating remained at the surface and there was little diffusion through the bulk. Antibacterial (Escherichia coli--13 mm and Staphylococcus epidermidis--12 mm) and antifungal testing (Candida albicans--7.7 mm) determined that small Ag-coated glass particles exhibited the largest inhibition zones compared to uncoated particles. pH analysis determined an overall higher pH consider in the smaller particles, where after 24 h the large uncoated and Ag coated particles were 8.27 and 8.74 respectively, while the smaller uncoated and Ag coated particles attained pH values of 9.63 and 9.35 respectively.

Evaluating antimicrobial efficacy and cost of 3 dressings containing silver versus a novel antimicrobial hydrogel impregnated gauze dressing containing Oakin, an oak extract.

PURPOSE: Antimicrobial wound dressings are becoming more popular and are routinely used in the treatment of chronic and problematic wounds. Despite the ever-growing number and types of these antimicrobial products, many practitioners often do not report significant clinical differences between various common antimicrobial wound dressings despite wide variations in cost. Although these dressings use different active ingredients or different presentations of a particular active ingredient, all attempt to protect the wound from bacterial colonization and promote wound repair. With so many topical antimicrobial dressings to choose from in the clinical setting (many having already fallen into disfavor due to their cytotoxic characteristics) it was of prime interest to determine if there was a substantial difference between some of the more commonly used antimicrobial dressings, with silver versus an antimicrobial wound dressing using Oakin (oak extract [Amerx Health Care Corporation, Clearwater, Florida]) as the active ingredient. METHODS: This article compares the antimicrobial efficacy of 4 commonly used wound dressings in vitro, utilizing a corrected zone of inhibition test followed by a cost analysis. RESULTS: In vitro testing demonstrated that there were no substantial differences in the corrected zone of inhibition measurements between the silver wound dressings and the less expensive Oakin-impregnated gauze dressing. CONCLUSION: Despite obvious limitations of this study, these results suggest that the biggest differences between many antimicrobial dressings on the market may be more in cost than in antimicrobial efficacy. The differences in cost are due to variances in cost per application and frequency of applications per week.

[Dressings for local treatment of leg ulcers]. / Pansements utilisés dans le traitement local des ulcères de jambe.

The beneficial effect of a moist wound environment has been well established for healing rate of acute wounds, pain relief and debridement of chronic wounds. Modern dressings are occlusive or semi occlusive, classified according to their physical composition and to their performances such as absorbent capacity, hydrating ability, adhesive components and debridement capacity. They are used to control the exudates and to maintain the wound in a moist environment. Published systematic reviews of the value of different types of dressings in the management of chronic wounds provide only weak levels of evidence of their clinical efficacy, in terms of healing rate. Nevertheless, the indications of modern dressings were recently determined according to a systematic review of the literature and to a formal consensus process. Despite the lack of appropriate studies, modern dressings remains a part of the standard of care and are widely used according to the experience of the clinicians, in larger indications than what may be recommended by evidence-based medicine.

Evaluating antimicrobial efficacy of new commercially available silver dressings.

Prevention and treatment of bacterial colonised/infected wounds are critical. Many commercially available silver dressings claim broad-spectrum bactericidal activity over days and are indicated for serious conditions including burns and ulcers. However, there is no peer-reviewed literature available for many newer dressings. This study compared the activity of some of these dressings. Six silver-containing dressings were compared using log reduction, silver release and corrected zone of inhibition assays. Only the nanocrystalline silver dressing was bactericidal against Staphylococcus aureus, and the only other dressing that produced any log reduction was a silver collagen matrix dressing. These two dressings and a silver alginate dressing produced zones of inhibition, although the collagen matrix and alginate dressings had decreasing zone sizes over time, and the latter liquefied after five transfers. The remaining dressings (two ionic silver foam dressings and a silver sulphate dressing) did not produce zones of inhibition. For the foam, alginate and collagen matrix dressings, antimicrobial activity was related to silver release. The silver sulphate dressing released large quantities of silver, but only through the dressing edges, as the wound-contacting surface appeared to be hydrophobic. The results of this study emphasise the importance of confirming product claims regarding silver dressing efficacy.

In vitro comparison of antimicrobial activity of iodine and silver dressings against biofilms.

OBJECTIVE: To compare the antimicrobial effectiveness of silver- and iodine-containing wound dressings against preformed mature biofilms of pathogenic wound bacteria grown in vitro. METHOD: Biofilms of Pseudomonas aeruginosa and Staphylococcus aureus were grown within an in vitro flat bed perfusion biofilm model. Mature biofilms were removed and exposed to wound dressings containing either silver or iodine (Aquacel Ag and Iodozyme) within a static diffusion method, for up to 24 hours. This method was designed to reflect certain key features that determine antimicrobial activity within the wound. The numbers of viable bacteria surviving in the biofilms were determined at set time intervals over the test period. RESULTS: Both test dressings exerted an antimicrobial effect against the target species biofilms, although the iodine dressing was more efficacious under the experimental conditions employed. CONCLUSION: There are large and potentially significant differences (as measured in vitro) in the effectiveness of wound dressings containing broad-spectrum antimicrobial agents such as silver and iodine against specific types of bacterial biofilms.

Evaluation of an antimicrobial silver foam dressing for use with V.A.C. therapy: morphological, mechanical, and antimicrobial properties.

The V.A.C. Therapy System (KCI, San Antonio, TX) is an integrated wound management system that creates an environment that promotes wound healing. V.A.C. GranuFoam Silver dressing (S-ROCF) is a reticulated, open-celled polyurethane foam having a pore size range of 400-600 microm. The foam is coated with silver to impart antimicrobial properties throughout the dressing. The morphological and key mechanical properties including tensile strength, ultimate elongation, tear strength, and compression resistance of this dressing were compared to the original V.A.C. GranuFoam dressing (ROCF), which is also a reticulated, open-celled polyurethane foam, and were found to be comparable. Furthermore, the antimicrobial property of S-ROCF was evaluated in vitro for efficacy against pathogens commonly found in clinical settings, including Staphylococcus aureus and Pseudomonas aeruginosa. S-ROCF was found to be effective during antimicrobial testing with a 99.99% reduction in colony forming units, and remained effective after 72 h of simulated V.A.C. Therapy. The antimicrobial and mechanical characteristics of the foam were unaffected by aging as demonstrated through an accelerated aging process. The V.A.C. GranuFoam Silver dressing is a specialized antimicrobial dressing for use with the V.A.C. Therapy System that exhibits morphological and mechanical properties comparable to the V.A.C. GranuFoam dressing and provides the added benefit of antimicrobial efficacy.

Acoustic pressure wound therapy in the treatment of stage II pressure ulcers.

Pressure ulcers are localized skin injuries secondary to unrelieved pressure or friction. Patients with immobility issues are at increased risk for developing pressure ulcers. In 2004, stricter federal regulations for prevention and treatment of pressure ulcers in institutional settings--eg, long-term care facilities--were introduced. Effective, low-cost treatments for pressure ulcers are needed; acoustic pressure wound therapy (APWT), a noncontact, low-frequency, therapeutic ultrasound system, is one option. A retrospective case series of six long-term care patients (two men and one woman, age range 61 to 92 years), each with one Stage II pressure ulcer, is presented. Acoustic pressure wound therapy was provided as an adjunct to standard treatment that included balsam of Peru/castor oil/trypsin ointment, hydrogel, hydrocolloid dressings, silver dressings, and offloading. Outcomes (days to healing) were determined through changes in wound dimensions. Study participants each received APWT for 3 to 4 minutes three to four times weekly. In four of the six wounds, the average number of days to healing was 22. One of the two remaining patients discontinued treatment at 95% healed; treatment for the sixth patient was ongoing due to hospitalization that delayed APWT. In a long-term care setting, APWT added to standard of care may accelerate healing of Stage II pressure ulcers.

A systematic review of wound cleansing for pressure ulcers.

AIM: The aim of this study was to use a Cochrane systematic review process to explore the effect of wound cleansing solutions and techniques on pressure ulcer healing. BACKGROUND: Pressure ulcers impose a significant financial burden on health care systems and negatively affect the quality of life. Wound cleansing is an important component of pressure ulcer care; however, there is uncertainty regarding best practice. DESIGN: Systematic review. METHODS: The Specialised Trials Register of the Cochrane Wounds Group, the Cochrane Central Register of Controlled Trials and bibliographies of relevant publications were searched. Drug companies and experts in the field were also contacted. Randomized controlled trials (RCTs) comparing wound cleansing with no wound cleansing, or different wound cleansing solutions, or different cleansing techniques, were eligible for inclusion. For dichotomous outcomes, relative risk (RR) plus 95% confidence intervals (CI) were calculated; for continuous outcomes, weighted mean difference plus 95% CI were calculated. Meta analysis was not conducted because of the small number of diverse RCTs identified. RESULTS: No studies compared cleansing with no cleansing. A statistically significant improvement in healing occurred for wounds cleansed with saline spray containing Aloe vera, silver chloride and decyl glucoside (Vulnopur) compared with isotonic saline (p = 0.025). No statistically significant change in healing was seen when water was compared with saline (RR 3.00, 95% CI 0.21, 41.89). No statistically significant change in healing was seen for ulcers cleansed with, or without, a whirlpool (RR 2.10, 95% CI 0.93-4.76). CONCLUSION: There is little trial evidence to support the use of any particular wound cleansing solution or technique for pressure ulcers. Relevance to clinical practice. No firm recommendations for ways of cleansing pressure ulcers in clinical practice can be made, the lack of RCT evidence should be a concern for health care providers.