The Wound-Healing Effect of Mango Peel Extract on Incision Wounds in a Murine Model.

Mangifera indica can generate up to 60% of polluting by-products, including peels. However, it has been shown that flavonoids and mangiferin are mainly responsible for the antioxidant, anti-inflammatory, and antibacterial activities closely related to the wound-healing process. The chemical composition of MEMI (methanolic extract of M. indica) was analyzed by HPLC-DAD, as well as concentrations of total phenol (TPC) and flavonoids (TFC) and antioxidant activity (SA50). Wound-healing efficacy was determined by measurements of wound contraction, histological analysis, and tensiometric method; moreover, anti-inflammatory, antibacterial, and acute dermal toxicity (OECD 402) were also evaluated. Phenol, resorcinol, conjugated resorcinol, and mangiferin were detected. TPC, TFC, and SA50 were 136 mg GAE/g, 101.66 mg QE/g, and 36.33 µg/mL, respectively. Tensile strength and wound contraction closure did not show significant differences between MEMI and dexpanthenol groups. Histological analysis (after 14 days) shows a similar architecture between MEMI treatment and normal skin. MEMI exhibits a reduction in edema. Staphylococcus epidermidis had an MIC of 2 mg/mL, while Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli reached 4 mg/mL. The MEMI showed no signs of toxicity. Therefore, this study demonstrates multiple targets that flavonoids and mangiferin of MEMI may present during the healing process.

Chitosan/Hyaluronic acid/Alginate and an assorted polymers loaded with honey, plant, and marine compounds for progressive wound healing-Know-how.

Biomaterials are being extensively used in regenerative medicine including tissue engineering applications, as these enhance tissue development, repair, and help in the process of angiogenesis. Wound healing is a crucial biological process of regeneration of ruptured tissue after getting injury to the skin and other soft tissue in humans and animals. Besides, the accumulation of microbial biofilms around the wound surface can increase the risk and physically obstruct the wound healing activity, and may even lead to amputation. Hence, in both acute and chronic wounds, prominent biomaterials are required for wound healing along with antimicrobial agents. This review comprehensively addresses the antimicrobial and wound healing effects of chitosan, chitin, cellulose acetate, hyaluronic acid, pullulan, bacterial cellulose, fibrin, alginate, etc. based wound dressing biomaterials fabricated with natural resources such as honey, plant bioactive compounds, and marine-based polymers. Due to their excellent biocompatibility and biodegradability, bioactive compounds derived from honey, plants, and marine resources are commonly used in biomedical and tissue engineering applications. Different types of polymer-based biomaterials including hydrogel, film, scaffold, nanofiber, and sponge dressings fabricated with bioactive agents including honey, curcumin, tannin, quercetin, andrographolide, gelatin, carrageenan, etc., can exhibit significant wound healing process in, diabetic wounds, diabetic ulcers, and burns, and help in cartilage repair along with good biocompatibility and antimicrobial effects. Among the reviewed biomaterials, carbohydrate polymers such as chitosan-based biomaterials are prominent and widely used for wound healing applications followed by hyaluronic acid and alginate-based biomaterials loaded with honey, plant, and marine compounds. This review first provides an overview of the vast natural resources used to formulate different biomaterials for the treatment of antimicrobial, acute, and chronic wound healing processes.

A New Look at the Purported Health Benefits of Commercial and Natural Clays.

Clays attributed to have medicinal properties have been used since prehistoric times and are still used today as complementary medicines, which has given rise to unregulated "bioceutical" clays to treat skin conditions. Recently, clays with antibacterial characteristics have been proposed as alternatives to antibiotics, potentially overcoming modern day antibiotic resistance. Clays with suggested antibacterial properties were examined to establish their effects on common wound-infecting bacteria. Geochemical, microscopical, and toxicological characterization of clay particulates, their suspensions and filtered leachates was performed on THP-1 and HaCaT cell lines. Cytoskeletal toxicity, cell proliferation/viability (MTT assays), and migration (scratch wounds) were further evaluated. Clays were assayed for antibacterial efficacy using minimum inhibitory concentration assays. All clays possessed a mineral content with antibacterial potential; however, clay leachates contained insufficient ions to have any antibacterial effects. All clay leachates displayed toxicity towards THP-1 monocytes, while clay suspensions showed less toxicity, suggesting immunogenicity. Reduced clay cytotoxicity on HaCaTs was shown, as many leachates stimulated wound-healing responses. The "Green" clay exhibited antibacterial effects and only in suspension, which was lost upon neutralization. pH and its interaction with clay particle surface charge is more significant than previously understood to emphasize dangers of unregulated marketing and unsubstantiated bioceutical claims.

The effect of combined curcumin-mediated photodynamic therapy and artificial skin on Staphylococcus aureus-infected wounds in rats.

Healing wounds represent a major public health problem, mainly when it is infected. Besides that, the antibiotics misuse and overuse favor the development of bacterial resistance. This study evaluated the effects of antimicrobial photodynamic therapy (aPDT) combined with artificial skin on disinfection of infected skin wound in rats. Twenty-four Wistar rats were randomly distributed into 4 groups (n = 6): (i) control-untreated; (ii) aPDT-treated with curcumin-mediated aPDT (blue light); (iii) artificial skin-treated with artificial skin alcohol-based; and (iv) aPDT plus artificial skin-treated with aPDT associated with artificial skin alcohol-based. For the in vivo model, a full-thickness biopsy with 0.80 cm was performed in order to inoculate the microorganism Staphylococcus aureus (ATCC 25923). The aPDT was performed with a curcumin gel and a blue LED light (450 nm, 80 mW/cm2) at the dose of 60 J/cm2 and the treatment with alcohol-based artificial skin was done with the topical application of 250 µL. Additional animals were submitted to aPDT combined with the artificial skin. After treatments, the number of colony-forming units (CFU) and the damage area were determined. Data were analyzed by two-way repeated measures ANOVA and Tukey tests. The highest reduction of the bacterial viability was observed in the PDT plus artificial skin group (4.14 log10), followed by artificial skin (2.38 log10) and PDT (2.22 log10) groups. In addition, all treated groups showed higher relative area of wound contraction (36.21% for the PDT, 38.41% for artificial skin, and 35.02% for PDT plus artificial) in comparison with the control group. These findings provide evidence for the positive benefits of aPDT with blue light and curcumin associated with artificial skin to decontaminate and accelerate the wound contraction.

The bactericidal efficacy of femtosecond laser-based therapy on the most common infectious bacterial pathogens in chronic wounds: an in vitro study.

We investigated the influence of femtosecond laser irradiation on the growth of the two most common infectious bacterial pathogens in wounds; Staphylococcus aureus and Pseudomonas aeruginosa as an attempt to validate optimum parameters for a laser-based bactericidal modality to be used clinically. Bacterial cultures were exposed to femtosecond laser irradiation at different wavelengths, exposure times, and laser powers. The source of femtosecond laser was INSPIRE HF100 laser system, Spectra-Physics, which is pumped by a mode-locked femtosecond Ti: sapphire laser MAI TAI HP, Spectra-Physics. After irradiation, bacterial cells' survival was monitored by observing the clear zones of inhibition in cultured agar plates. Results for all strains indicated that the exposure to femtosecond laser irradiation with a wavelength ranging from ultraviolet (λ > 350 nm) to blue laser light (λ < 480 nm), for a period above 20 min and with a power density of ≈ 0.063 W/cm2, was enough to inhibit both bacterial pathogens with the results maintained for 1 week following irradiation.

Synergistic Effect and Antibiofilm Activity of a Skin and Wound Cleanser.

INTRODUCTION: Biofilm in chronic wounds impedes the wound healing process. Each biofilm has differing characteristics requiring a multifaceted approach for removal while maintaining a surrounding environment conducive to wound healing. OBJECTIVE: In this study, 3 of the components in a wound cleanser are tested to determine synergy in eradicating biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in vitro. MATERIALS AND METHODS: The 3 components assessed for synergy were ethylenediamine tetraacetic acid sodium salts (EDTA), vicinal diols (VD; ethylhexylglycerin and octane-1,2-diol), and polyhexamethylene biguanide (PHMB). Each component was assessed individually and in combination while dissolved in a base solution. The Calgary assay method was used for biofilm growth and treatment. Kull Equation analysis for synergy was conducted using viable count results. RESULTS: Synergy is defined as the interaction of components to produce a combined effect greater than the sum of their separate effects. The base solution containing all 3 components (EDTA, VD, and PHMB) reduced biofilm viability by more than 5 logs, demonstrating statistically significant synergy. The 3 components tested individually in the base solution resulted in the following: EDTA did not reduce bacteria viability; VD reduced viability by about 1 log; and PHMB reduced P aeruginosa viability by about 2.5 logs and MRSA viability by about 4 logs. Of importance, the MRSA biofilm failed to regrow in the recovery plates after combined treatment, indicating complete elimination of the biofilm bacteria. CONCLUSIONS: The experimental and calculated results indicate the 3 components (VD, EDTA, and PHMB) when used together act synergistically to eradicate MRSA and P aeruginosa biofilms in vitro.

Quinine Enhances Photo-Inactivation of Gram-Negative Bacteria.

BACKGROUND: Antimicrobial resistance is a significant concern to public health, and there is a pressing need to develop novel antimicrobial therapeutic modalities. METHODS: In this study, we investigated the capacity for quinine hydrochloride (Q-HCL) to enhance the antimicrobial effects of antimicrobial blue light ([aBL] 405 nm wavelength) against multidrug-resistant (MDR) Gram-negative bacteria in vitro and in vivo. RESULTS: Our findings demonstrated the significant improvement in the inactivation of MDR Pseudomonas aeruginosa and Acinetobacter baumannii (planktonic cells and biofilms) when aBL was illuminated during Q-HCL exposure. Furthermore, the addition of Q-HCL significantly potentiated the antimicrobial effects of aBL in a mouse skin abrasion infection model. In addition, combined exposure of aBL and Q-HCL did not result in any significant apoptosis when exposed to uninfected mouse skin. CONCLUSIONS: In conclusion, aBL in combination with Q-HCL may offer a novel approach for the treatment of infections caused by MDR bacteria.

Polyurethane-biomacromolecule combined foam dressing containing asiaticoside: fabrication, characterization and clinical efficacy for traumatic dermal wound treatment.

Polyurethane combined (PUC) foam dressings with various biomacromolecules were fabricated with the adsorption of asiaticoside and silver nanoparticles for traumatic wound treatment. Biomacromolecules had varying effects on physicochemical and mechanical properties of PU foam. With 2% incorporation, starches, high molecular weight chitosan and gelatin provided stiffer and more porous foams while carboxymethylcellulose had the highest compression strength but the lowest water vapor transmission. High water absorption was from foams with carboxymethylcellulose, alginate, hydroxypropyl methylcellulose and low molecular weight chitosan. Increasing the concentrations up to 12% had more prominent effect. However, powdery surface was noticed with poorer tensile properties that 6% incorporation was selected. FTIR spectra and DSC thermograms suggested interaction of PU formulation with biomacromolecules. EDS analysis confirmed existence of active compounds while acceptable stability was from sterilized PUC foam with alginate. On healthy volunteers, this selected foam dressing caused no skin irritation and retained moisture comparable to commercial product. In patients with traumatic dermal wounds, healing improvement with shorter wound closure time, higher reepithelialization and less pain score were from the selected foam dressing compared to standard gauze soaked with chlorhexidine. This PU-alginate combined foam dressing adsorbed with asiaticoside and silver nanoparticles proved advantages for traumatic dermal wound management.

Nitrogen-doped carbon quantum dots as an antimicrobial agent against Staphylococcus for the treatment of infected wounds.

Antimicrobial resistance is becoming more and more serious and has become a potential hazard to human life and health. The fabrication of some new antibacterial substances against resistant bacteria is demanded. With the wide application and research of carbon nanomaterials, nitrogen-doped carbon quantum dots (NCQDs) were synthesized by a one-step chemical route herein. The particle size of NCQDs in the range of 2-5 nm were characterized by transmission electron microscopy (TEM), atomic force microscopy, and dynamic light scattering. The functional groups and optical properties of NCQDs were investigated by UV-vis absorption spectroscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Disk-diffusion tests showed that the NCQDs had specific antibacterial activity against Staphylococcus. TEM showed that the NCQDs could destroy the cell structure of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) but could not combat Escherichia coli. The antibacterial mechanism may be that positively charged NCQDs firstly interacted with the negatively charged bacteria, and then specifically anchored on some specific sites on the surface of Staphylococcus. The NCQDs were applied to treat wounds infected with MRSA and showed the same therapeutic effect as vancomycin. Photomicrographs of hematoxylin-eosin-stained histological sections showed that the NCQDs at concentrations effectively killing S. aureus and MRSA caused negligible toxicity to the main rat organs, including heart, liver, spleen, lung, and kidney. Thus, the NCQDs can be developed as a promising antibacterial agent for Staphylococcus. And the NCQDs are likely to treat local infections caused by Staphylococcus clinically, especially S. aureus and MRSA.

Wound healing potential of oil extracted from Parrotiopsis jacquemontiana (Decne) Rehder.

ETHNOPHARMACOLOGICAL RELEVANCE: Oil extracted from Parrotiopsis jacquemontiana stem traditionally used for wound healing, body aches and dermatitis. In this study we have evaluated oil for its phytoconstituents, antioxidant, antimicrobial and wound healing activities. METHODS: Phytochemical characterization of oil was determined by standard qualitative procedures, gas chromatography mass spectrometry technique (GC-MS) and Fourier transform infra-red spectroscopy (FT-IR). The in vitro antioxidant aptitude was determined by scavenging of DPPH radical, hydroxyl ion, nitric oxide, inhibition of ß-carotene bleaching assay and iron chelation power assay. The antimicrobial potential of oil was investigated by disc diffusion method against multidrug resistant (MDR) bacterial isolates and fungal strains. Wound healing was performed in vivo with determination of wound contraction rates, histopathology, hemostatic potential and hydroxyproline estimation. RESULTS: GC-MS analysis indicated that oil was constituted mainly of 2, 6-dimethyl-8-oxoocta-2, 6-dienoic acid, methyl ester (18.2%), syringol (17.8%), catechol (12.4%), guaiacol (5.2%), p-cresol (5.4%) and phenol, 2-propyl- (3.7%). FT-IR analysis revealed several important functional groups in its chemical composition especially phenolic O-H compound stretching. Scavenging of DPPH radical, hydroxyl ion, nitric oxide, inhibition of ß-carotene oxidation and iron chelation power assays indicated strong antioxidant activities of oil. Further it efficiently inhibited growth of multidrug resistant isolates of Staphylococcus aureus, S. lugdenesis, Klebsiella pneumoniae, Escherichia coli, Coagulase -ve staphylococci and Pseudomonas aeruginosa. The minimum inhibitory concentrations ranged between (32-256) (µg/mL) of oil. The oil also strongly inhibited the growth of various fungal isolates with low level of minimum inhibitory concentrations (64-256) µg/mL. Remarkable rate for wound closure and epithelization, hemostatic potential and marked increase (p < 0.05) in hydroxyproline content was observed for oil during wound healing in rat. CONCLUSION: The results suggested that oil can be used as a potential source of wound healing therapeutics.

The impact of ethanol extract of propolis on biofilm forming by Proteus Mirabilis strains isolated from chronic wounds infections.

Alcoholic propolis extracts may be used to eliminate microbes in mucous membranes and skin inflammations and in wound infections. The aim of this study was an assessment of the ethanol extract of propolis (EEP) activity against biofilm formation by P. mirabilis. Six clinical strains of P. mirabilis isolated from patients with chronic wound infection, and one reference strain of P. mirabilis ATCC 29906 were used. Biofilm was formed in 96-well plate. In order to evaluate the effect of EEP at a concentration range of 1.56-100 mg/mL on the forming and mature biofilm, P. mirabilis cells were released by sonication. In this study the effectiveness of 25-100 mg/mL of EEP on the forming P. mirabilis biofilm and concentrations of 25-50 mg/mL of EEP on formed biofilm has been demonstrated. Our results suggest the possibility of using the EEP in treatment of chronic wound infection caused by P. mirabilis.

Anti-Pathogenic Efficacy and Molecular Targets of a Polyherbal Wound- Care Formulation (Herboheal) Against Staphylococcus aureus.

BACKGROUND: A polyherbal formulation (Herboheal) traditionally indicated for woundcare was investigated for its anti-virulence potential against the notorious pathogen Staphylococcus aureus. OBJECTIVE: This study aimed at evaluating anti-virulence potential of Herboheal formulation against S. aureus in vitro as well as in vivo, followed by studying its effect on target bacterium's gene expression at the whole transcriptome level. METHODS: In vitro efficacy of the test formulation was evaluated using broth dilution assay, whereas in vivo efficacy was assayed employing the nematode Caenorhabditis elegans as the model host. Molecular targets of the test formulation in S. aureus were elucidated through whole transcriptome analysis. RESULTS: This formulation could exert inhibitory effect on bacterial growth and quorum sensingregulated pigment (staphyloxanthin) production at ≥ 0.025% v/v. It not only could inhibit S. aureus biofilm formation, but also eradicated pre-formed biofilm effectively. This formulation could modulate antibiotic susceptibility of S. aureus, enhanced its susceptibility to human serum heavily, while compromising its haemolytic potential. Herboheal-treated bacteria expressed notably lesser virulence towards the nematode worm Caenorhabditis elegans. Even repeated exposure of S. aureus to this polyherbal formulation did not give rise to resistant phenotype. Whole transcriptome analysis revealed genes associated with hemolysis, virulence, enzyme activity, transport, basic cellular processes, quorum sensing, and transcriptional regulators as the major targets of Herboheal in S. aureus. CONCLUSION: This study validates the traditional use of Herboheal formulation in wound-care by demonstrating its efficacy against one of the pathogenic bacteria most commonly involved in wound infections.

Treatment Strategies for Infected Wounds.

The treatment of skin wounds is a key research domain owing to the important functional and aesthetic role of this tissue. When the skin is impaired, bacteria can soon infiltrate into underlying tissues which can lead to life-threatening infections. Consequently, effective treatments are necessary to deal with such pathological conditions. Recently, wound dressings loaded with antimicrobial agents have emerged as viable options to reduce wound bacterial colonization and infection, in order to improve the healing process. In this paper, we present an overview of the most prominent antibiotic-embedded wound dressings, as well as the limitations of their use. A promising, but still an underrated group of potential antibacterial agents that can be integrated into wound dressings are natural products, especially essential oils. Some of the most commonly used essential oils against multidrug-resistant microorganisms, such as tea tree, St. John's Wort, lavender and oregano, together with their incorporation into wound dressings are presented. In addition, another natural product that exhibits encouraging antibacterial activity is honey. We highlight recent results of several studies carried out by researchers from different regions of the world on wound dressings impregnated with honey, with a special emphasis on Manuka honey. Finally, we highlight recent advances in using nanoparticles as platforms to increase the effect of pharmaceutical formulations aimed at wound healing. Silver, gold, and zinc nanoparticles alone or functionalized with diverse antimicrobial compounds have been integrated into wound dressings and demonstrated therapeutic effects on wounds.

Bioelectric Dressing Supports Complex Wound Healing in Small Animal Patients.

It is well documented that physiological electric fields provide the earliest signals necessary to initiate cell proliferation, migration, and ultimately reepithelialization of wounds. Additionally, electricity is known to exert an antimicrobial effect. An electric field-generating wound dressing designed to mimic physiological electric fields has not been described in the small animal clinic. This article retrospectively reviews the use of a microcell battery-impregnated bioelectric dressing (BED) in 5 small animal patients with complex wounds. For each patient, product application and wound healing progress was monitored and documented over several weeks. Despite the severity of the wounds and being at high risk for infection, all presenting wounds treated with BED achieved complete closure within 4 weeks without becoming infected or requiring grafting. These cases provide early evidence that the use of the BED is feasible in a small animal clinic and may support healing while providing topical, nonantibiotic activity against wound pathogens.

Antibacterial activity of 3, 3', 4'-Trihydroxyflavone from Justicia wynaadensis against diabetic wound and urinary tract infection

ABSTRACT The present investigation was designed to study the effect of an active compound isolated from Justicia wynaadensis against multi drug resistant organisms (MDRO's) associated with diabetic patients. The drug resistant pathogens implicated in wound and urinary tract infection of diabetic patients were isolated and identified by molecular sequencing. Solvent-solvent fractionation of crude methanol extract produced hexane, chloroform, ethyl acetate and methanol-water fraction, among which chloroform fraction was found to be potent when compared with other three fractions. Further, chloroform fraction was subjected to preparatory HPLC (High-Performance Liquid Chromatography), that produced four sub-fractions; chloroform HPLC fraction 1 (CHF1) through CHF4. Among the sub-fractions, CHF1 inhibited the pathogens effectively in comparison to other three sub-fractions. The purity of CHF1 was found to be >95%. Therefore, CHF1 was further characterized by NMR and FTIR analysis and based on the structure elucidated, the compound was found to be 3,3',4'-Trihydroxyflavone. The effective dose of this bioactive compound ranged from 32 µg/mL to 1.2 mg/mL. Thus, the present study shows that 3,3',4'-Trihydroxyflavone isolated from J. wynaadensis is an interesting biopharmaceutical agent and could be considered as a source of antimicrobial agent for the treatment of various infections and used as a template molecule for future drug development.

Antibacterial activity of 3,3',4'-Trihydroxyflavone from Justicia wynaadensis against diabetic wound and urinary tract infection.

The present investigation was designed to study the effect of an active compound isolated from Justicia wynaadensis against multi drug resistant organisms (MDRO's) associated with diabetic patients. The drug resistant pathogens implicated in wound and urinary tract infection of diabetic patients were isolated and identified by molecular sequencing. Solvent-solvent fractionation of crude methanol extract produced hexane, chloroform, ethyl acetate and methanol-water fraction, among which chloroform fraction was found to be potent when compared with other three fractions. Further, chloroform fraction was subjected to preparatory HPLC (High-Performance Liquid Chromatography), that produced four sub-fractions; chloroform HPLC fraction 1 (CHF1) through CHF4. Among the sub-fractions, CHF1 inhibited the pathogens effectively in comparison to other three sub-fractions. The purity of CHF1 was found to be >95%. Therefore, CHF1 was further characterized by NMR and FTIR analysis and based on the structure elucidated, the compound was found to be 3,3',4'-Trihydroxyflavone. The effective dose of this bioactive compound ranged from 32µg/mL to 1.2mg/mL. Thus, the present study shows that 3,3',4'-Trihydroxyflavone isolated from J. wynaadensis is an interesting biopharmaceutical agent and could be considered as a source of antimicrobial agent for the treatment of various infections and used as a template molecule for future drug development.

Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential.

The present paper investigated the efficiency of Urtica dioica (U. dioica) on hemostatic and wound healing activities. U. dioica leaf extracts were evaluated for their antibacterial and antioxidant effects as well as their flavonoid and polyphenol content. The hydroethanolic extract (EtOH-H2OE), showing the most potent antibacterial and antioxidant activities in vitro, thanks to its flavonoid and polyphenol richness, was selected for hemostatic and wound healing evaluation. Twenty-four rats completing full-thickness wounds were split into four groups. The wounds were topically treated with saline solution, glycerol, "CICAFLORA," and U. dioica EtOH-H2OE (50 µL/mm2) until day 11. The wound healing effect was assessed by macroscopic, histological, and biochemical parameters. Rats treated with EtOH-H2OE showed fast wound closure (92.39%) compared to the control animals (60.91%) on the 11th day of wounding (P < 0.01). Histopathological and biochemical explorations showed full epidermal regeneration and an improvement of the hydroxyproline content in the U. dioica EtOH-H2OE treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of unsaturated fatty acids and a high concentration of lupeol known for their involvement in reepithelialization. These results prove the efficiency of U. dioica EtOH-H2OE in wound healing and supported its traditional use.

On-demand Antimicrobial Treatment with Antibiotic-Loaded Porous Silicon Capped with a pH-Responsive Dual Plasma Polymer Barrier.

Chronic wounds are a major socio-economic problem. Bacterial infections in such wounds are a major contributor to lack of wound healing. An early indicator of wound infection is an increase in pH of the wound fluid. Herein, we describe the development of a pH-responsive drug delivery device that can potentially be used for wound decontamination in situ and on-demand in response to an increase in the pH of the wound environment. The device is based on a porous silicon film that provides a reservoir for encapsulation of an antibiotic within the pores. Loaded porous silicon is capped with dual plasma polymer layers of poly(1,7-octadiene) and poly(acrylic acid), which provide a pH-responsive barrier for on-demand release of the antibiotic. We demonstrate that release of the antibiotic is inhibited in aqueous buffer at pH 5, whereas the drug is released in a sustainable manner at pH 8. Importantly, the released drug was bacteriostatic against the Pseudomonas aeruginosa wound pathogen. In the future, incorporation of the delivery device into wound dressings could potentially be utilized for non-invasive decontamination of wounds.

Bacterial flora of combat wounds from eastern Ukraine and time-specified changes of bacterial recovery during treatment in Ukrainian military hospital.

BACKGROUND: Microbiology of modern war wounds is unique for each military conflict. Climatic and geographical features of the theater of war, contemporary warfare as well as wound management affect the microbial flora of wounds. This study was designed to determine time-specific microbial flora of combat wounds of upper and lower extremities obtained during the war in eastern Ukraine. METHODS: The patients enrolled in study had combat wounds of upper or lower extremities which were treated in the Military Medical Clinical Center of Central Region. The wounds were swab-cultured and measured at each surgical debridement. The recovered microorganisms were identified and their antimicrobial resistance profiles were evaluated by disc diffusion method. RESULTS: Forty-nine patients with battle-field wounds were enrolled in the study from July to November 2014; all patients were male with a mean Injury Severity Score and arrival APACHE II scores of 16.2 ± 10.7 and 7.4 ± 4.2 respectively. Among 128 swab cultures, 100 swab cultures were positive. Swab cultures were obtained from 57 wounds of 49 patients. The results of the test showed that 87.7% of all positive swab cultures contained a single-organism while the rest of the swab-culture results showed polymicrobial growth. Among the isolated microorganisms 65% (76 strains) were Gram-negative rods, 22.2% (26 strains) of Gram-positive cocci, followed by Gram-positive rods (12.8%, 15 strains). We found that epidemiology of wound infection changes with the time after injury. The most common bacterial isolates cultured during the first week were Gram-positive microbes with low pathogenicity. The number of Gram-negative rods increased during the wound healing process. The incidence of Gram-positive microorganisms' growth fell after the first week and increased after third week. During wound healing, bacterial microflora of wounds changes with increasing number of Gram-negative rods with predominance of Acinetobacter species. Predominant microorganisms in positive swab-cultures after first week were nonfermentative Gram-negative bacilli (68% of swab-cultures), which in 53% of the swab-cultures belonged to the genus Acinetobacter, and in 15% to the genus Pseudomonas. The incidence of polymicrobial wound cultures increased from first week to second post-injury week. The most frequent microbial mixture were Acinetobacter baumannii with Enterobacteriaceae or other nonfermentative Gram negative rods with Enterococcus spp. We observed bacteria recovery from wounds during proliferation phase. These wounds had no pure inflammation signs and were free of devitalized tissues. CONCLUSIONS: Any wound is at some risk of becoming infected. In the event of infection, a wound fails to heal, treatment costs rise, and general wound management practices become more resource demanding. Determining the microorganisms which colonize battle wounds and cause wound infection is paramount. This information can help to treat battle wound infections or even changes infection control strategies. The fact of shifting in wound microbiology in the favor of bacteria responsible for healthcare-associated infections support to the proposition that these changes are nosocomially related [4, 14]. For Ukrainian military medicine this study is the first time-specified assessment of battle wound colonization from the World War II.

Hyperosmotic Agents and Antibiotics Affect Dissolved Oxygen and pH Concentration Gradients in Staphylococcus aureus Biofilms.

Biofilms on wound surfaces are treated topically with hyperosmotic agents, such as medical-grade honey and cadexomer iodine; in some cases, these treatments are combined with antibiotics. Tissue repair requires oxygen, and a low pH is conducive to oxygen release from red blood cells and epithelialization. We investigated the variation of dissolved oxygen concentration and pH with biofilm depth and the variation in oxygen consumption rates when biofilms are challenged with medical-grade honey or cadexomer iodine combined with vancomycin or ciprofloxacin. Dissolved oxygen and pH depth profiles in Staphylococcus aureus biofilms were measured using microelectrodes. The presence of cadexomer iodine with vancomycin or ciprofloxacin on the surface of the biofilm permitted a measurable concentration of oxygen at greater biofilm depths (101.6 ± 27.3 µm, P = 0.02; and 155.5 ± 27.9 µm, P = 0.016, respectively) than in untreated controls (30.1 µm). Decreases in pH of ∼0.6 and ∼0.4 units were observed in biofilms challenged with medical-grade honey alone and combined with ciprofloxacin, respectively (P < 0.001 and 0.01, respectively); the number of bacteria recovered from biofilms was significantly reduced (1.26 log) by treatment with cadexomer iodine and ciprofloxacin (P = 0.002) compared to the untreated control. Combining cadexomer iodine and ciprofloxacin improved dissolved oxygen concentration and penetration depth into the biofilm, while medical-grade honey was associated with a lower pH; not all treatments established a bactericidal effect in the time frame used in the experiments.IMPORTANCE Reports about using hyperosmotic agents and antibiotics against wound biofilms focus mostly on killing bacteria, but the results of these treatments should additionally be considered in the context of how they affect physiologically important parameters, such as oxygen concentration and pH. We confirmed that the combination of a hyperosmotic agent and an antibiotic results in greater dissolved oxygen and reduced pH within an S. aureus biofilm.