Burn Wound Infection Research Articles

Engineered Superinfective Pf Phage Prevents Dissemination of Pseudomonas aeruginosa in a Mouse Burn Model.

Pf is a filamentous bacteriophage integrated in the chromosome of most clinical isolates of Pseudomonas aeruginosa. Under stress conditions, mutations occurring in the Pf genome result in the emergence of superinfective variants of Pf (SI-Pf) that are capable of circumventing phage immunity; therefore, SI-Pf can even infect Pf-lysogenized P. aeruginosa. Here, we identified specific mutations located between the repressor and the excisionase genes of Pf4 phage in the P. aeruginosa PAO1 strain that resulted in the emergence of SI-Pf. Based on these findings, we genetically engineered an SI-Pf (eSI-Pf) and tested it as a phage therapy tool for the treatment of life-threatening burn wound infections caused by PAO1. In validation experiments, eSI-Pf was able to infect PAO1 grown in a lawn as well as biofilms formed in vitro on polystyrene. eSI-Pf also infected PAO1 present in burned skin wounds on mice but was not capable of maintaining a sustained reduction in bacterial burden beyond 24 h. Despite not lowering bacterial burden in burned skin tissue, eSI-Pf treatment completely abolished the capability of P. aeruginosa to disseminate from the burn site to internal organs. Over the course of 10 days, this resulted in bacterial clearance and survival of all treated mice. We subsequently determined that eSI-Pf induced a small-colony variant of P. aeruginosa that was unable to disseminate systemically. This attenuated phenotype was due to profound changes in virulence determinant production and altered physiology. Our results suggest that eSI-Pf has potential as a phage therapy against highly recalcitrant antimicrobial-resistant P. aeruginosa infections of burn wounds. IMPORTANCE Pseudomonas aeruginosa is a major cause of burn-related infections. It is also the most likely bacterial infection to advance to sepsis and result in burn-linked death. Frequently, P. aeruginosa strains isolated from burn patients display a multidrug-resistant phenotype necessitating the development of new therapeutic strategies and prophylactic treatments. In this context, phage therapy using lytic phages has demonstrated exciting potential in the control P. aeruginosa infection. However, lytic phages can present a set of drawbacks during phage therapy, including the induction of bacterial resistance and limited bacteria-phage interactions in vivo. Here, we propose an alternative approach to interfere with P. aeruginosa pathogenesis in a burn infection model, i.e., by using an engineered superinfective filamentous phage. Our study demonstrates that treatment with the engineered Pf phage can prevent sepsis and death in a burn mouse model.

Antimicrobial photodynamic therapy: modern technology in the treatment of wound infections in patients with burns.

Staphylococcus aureus is one of the most frequently isolated microorganisms from burn wounds. Antimicrobial photodynamic therapy (aPDT) is a new strategy that may improve antimicrobial treatment. This study evaluated three meticillin-resistant Staphylococcus aureus (MRSA) and three meticillin-sensitive Staphylococcus aureus (MSSA) clinical isolates, which produced a biofilm with 0.1mg/ml Toluidine Blue O (TBO) (Sigma-Aldrich, Germany) with an energy density of 45J/cm2 and 90J/cm2, for MRSA and MSSA, respectively. The antibiofilm potential of aPDT with TBO was analysed using crystal violet assays and scanning electron microscopy. TBO-aPDT significantly degraded the biofilm formed by MRSA and MSSA clinical isolates (p<0.05). Our results indicated that aPDT is an effective approach to combat bacterial biofilms associated with burn wound infection. aPDT could provide a supplemental to the treatment of wound and tissue infection, and patients with burns may benefit from combined treatments.

The Use of Negative Pressure Wound Therapy in Infected Burn Wounds: Bridging the Gap

The Use of Negative Pressure Wound Therapy in Infected Burn Wounds: Bridging the Gap

Патогенез инфицированной ожоговой раны у крыс

Burns are a severe and widespread type of injury and are accompanied by local and systemic complications, leading to disability and death. Infection is a major complication of burn injury because thermal burns can cause disturbances of humoral and cellular immunity, and necrotized tissue ceases to perform its normal barrier function, which leads to the development of infection caused by environmental opportunistic microorganisms and commensals, which limits the ability of the skin to heal. In addition, the scab of a burn wound is a nutrient-rich environment that is easily colonized by microorganisms. Gram-positive bacteria are the first colonizers of the wound bed because they make up the microflora of the skin microbiome. Burn wounds are most commonly associated with Staphylococcus aureus, which is capable of producing virulence factors that slow wound healing. The frequency of thermal injuries and their subsequent infection necessitates the creation of new therapeutic agents as well as the development and adaptation of relevant model systems for preclinical studies. A sufficient number of in vivo models have been developed to study the pathogenesis of burn injuries, as well as to conduct specific studies as part of preclinical studies of potential therapeutic agents. Rats are an adaptable model for reproducing infected burn wounds and evaluating their course. The aim of the study was to evaluate the pathogenesis of infected burns, allowing further use of this model pathology in the study of a wide range of potential antiseptic and anti-burn agents. The study successfully generated a model of infected skin burn in Wistar rats. Creation of burn wounds was carried out by contact method, the inducing damage temperature was 100 °C, Staphylococcus aureus ATCC 25923 was used as an infectious agent. Evaluation of the dynamics of the course of an infected burn wound was carried out according to the results of planimetric, microbiological, cytological and histological studies. The developed model of an infected skin burn in rats is relevant to study the pharmacological activity of antiseptic agents and local anti-burn agents with an antimicrobial component of the mechanism of action.

A Bacteriological study on burn wound infections with implementation of the available infection control measures at the Burn Unit, Tanta University Hospital

A Bacteriological study on burn wound infections with implementation of the available infection control measures at the Burn Unit, Tanta University Hospital

Suprathel® or Mepilex® Ag for treatment of partial thickness burns in children: A case control study

AimThe study aim was to investigate if Suprathel® can be an adequate alternative to Mepilex® Ag for the treatment of partial-thickness scalds in children. MethodsA retrospective study including 58 children admitted to The Burn Centre in Linköping, Sweden between year 2015 and 2022. Of the 58 children, 30 were dressed with Suprathel ® and 28 with Mepilex ® Ag. Outcomes investigated were healing time, burn wound infection (BWI), need for operations and number of dressing changes. ResultsWe found no significant differences in any of the outcomes. In the Suprathel ® group 17 children and in the Mepilex ® Ag group 15 children were healed within 14 days. Ten children from each group received antibiotics for suspected BWI and two from each group underwent an operation with skin grafting. Each group had on median four dressing changes. ConclusionsTwo different treatments were compared for children with partial-thickness scalds, and the data indicates that similar results are received with both dressings.

Flagellar motility mediates biofilm formation in Aeromonas dhakensis

Aeromonas dhakensis possesses dual flagellar systems for motility under different environments. Flagella-mediated motility is necessary for biofilm formation through an initial attachment of bacteria to the surface, but this has not been elucidated in A. dhakensis. This study investigates the role of polar (flaH, maf1) and lateral (lafB, lafK and lafS) flagellar genes in the biofilm formation of a clinical A. dhakensis strain WT187 isolated from burn wound infection. Five deletion mutants and corresponding complemented strains were constructed using pDM4 and pBAD33 vectors, respectively, and analyzed for motility and biofilm formation using crystal violet staining and real-time impedance-based assays. All mutants were significantly reduced in swimming (p < 0.0001), swarming (p < 0.0001) and biofilm formation using crystal violet assay (p < 0.05). Real-time impedance-based analysis revealed WT187 biofilm was formed between 6 to 21 h, consisting of early (6–10 h), middle (11–18 h), and late (19–21 h) stages. The highest cell index of 0.0746 was recorded at 22–23 h and biofilms began to disperse starting from 24 h. Mutants Δmaf1, ΔlafB, ΔlafK and ΔlafS exhibited reduced cell index values at 6–48 h when compared to WT187 which indicates less biofilm formation. Two complemented strains cmaf1 and clafB exhibited full restoration to wild-type level in swimming, swarming, and biofilm formation using crystal violet assay, hence suggesting that both maf1 and lafB genes are involved in biofilm formation through flagella-mediated motility and surface attachment. Our study shows the role of flagella in A. dhakensis biofilm formation warrants further investigations.

Novel recombinant endolysin ointment with broad antimicrobial activity against methicillin-resistant Staphylococcus aureus isolated from wounds and burns.

The major problem in the management of burn wounds is infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of infection in burn wounds. Antibiotic-resistant bacteria around the world have become a major therapeutic challenge. Bacteriophages and their lysin are suggested as an antimicrobial alternative agent. The approach of this study was to evaluate the potential of recombinant phage lysin ointment efficacy in MRSA burn wound infection invitro. Whole genome sequencing was performed to the three isolated bacteriophages by ABM, USA using Illumina next-generation sequencing (NGS) technology. De novo assembly and genetic analysis carried out. Expression of lysin genes was performed by cloning using Escherichia coli JM109. Lysin protein extraction and purification was performed before and after cloning using precipitation by ammonium sulfate, dialysis, and gel filtration chromatography. Dose-dependent assay and time-kill curve experiment was performed for 2 lysins showed that recombinant lysin 2 functions more than its non-recombinant lysins 2 with the same concentration of 0.5µg/mL. Both lysins' ointment was prepared and compared with commercial ointments. 62 (78.4%) out of 79 wounds a burns swabs were detected as S. aureus and S methicillin-resistant S. aureus (MRSA) rate was determined to be 29 (46.8%) in total, while 33 isolates (53.2%) determined as methicillin-sensitive S. aureus (MSSA). According to the antibiotic susceptibility test results, all S. aureus isolates were identified as sensitive against vancomycin, ceftaroline, and linezolid. Results shows one lysogenic bacteriophage and three distinct lyticspecific S. aureus bacteriophage were isolated from sewage. For each of the three samples, a single contig was possible to be obtained. Sample BP-SA2 had the best coverage, and the contig was slightly longer than the other bacteriophages. In addition, BLAST search identified Staphylococcus bacteriophage vB-SscM-1 (accession KX171212.1) as the closest match to the public database. Finally, the gene annotation was checked, and two potential lysin genes were identified. Besides the two ends, there are only 4 SNPs between the three genomes. It should be noted that the two lysin genes from the genomes have no SNPs, and are identical across the three genomes. It can be seen that the three bacteriophages (BP-SA1), (BP-SA 2), and (BP-SA3) form their own tight cluster. It can be seen that (BP-SA 2) is more closely related to Staphylococcus bacteriophage vB-SscM-1 genome and most noticeable 5' region of S5 and vB-SscM-1 are now located at 3' end of vB-Sau-Clo6. The investigation of the two lysin genes in (BP-SA 2) by whole genome sequencing showed that there is some homology with vB-SscM-1; although the first gene is annotated as hypothetical protein, the second gene is annotated as amidase. The same two lysin genes are identified in all three bacteriophage genomes by the RAST. The putative protein sequences of the discovered phage lysin was analyzed using protein search with UniProt/Swiss-Prot database, and all matches suggest that the putative protein of the discovered phage lysin is a real endolysin. The three samples of bacteriophage were harboring both (Lysin 1 and lysin 2) genes were amplified. Afterward, 2-lysin genes were cloned successfully; for the dose-dependent assay, the same incubation time of recombinant lysins and its two non-recombinant lysins with the bacteria for 30min. It is found that the bactericidal activity of these groups increased in correlation with their concentrations. For the time-kill curve experiment, it showed that Recombinant lysin 2 functions more than its non-recombinant lysins 2 with the same concentration of 0.5µg/mL. Both lysins' ointments have potential activity against S. aureus isolates more than mupirocin and have a similar activity with Fusidic acid through applying 10µL from lysin 1 ointment, lysin 2 ointment, mupirocin ointment 2%, and Fusidic acid cream 2%. In vitro lytic spectrum analysis revealed that 100% (29/29) tested S. aureus were sensitive. One dose of lysin ointment resulted in a reduction of 3.3 log units in the number of bacteria (from an initial count of 2×105CFU/mg) at 18hours compared with one dose of mupirocin, PBS, or Aquaphor. Specifically, this study provides evidence that the application of lysin ointment has significant potential as an alternative strategy for MRSA infections.

Aptamers as Novel Binding Molecules on an Antimicrobial Peptide-Armored Composite Hydrogel Wound Dressing for Specific Removal and Efficient Eradication of Pseudomonas aeruginosa

Here we present for the first time a potential wound dressing material implementing aptamers as binding entities to remove pathogenic cells from newly contaminated surfaces of wound matrix-mimicking collagen gels. The model pathogen in this study was the Gram-negative opportunistic bacterium Pseudomonas aeruginosa, which represents a considerable health threat in hospital environments as a cause of severe infections of burn or post-surgery wounds. A two-layered hydrogel composite material was constructed based on an established eight-membered focused anti-P. aeruginosa polyclonal aptamer library, which was chemically crosslinked to the material surface to form a trapping zone for efficient binding of the pathogen. A drug-loaded zone of the composite released the C14R antimicrobial peptide to deliver it directly to the bound pathogenic cells. We demonstrate that this material combining aptamer-mediated affinity and peptide-dependent pathogen eradication can quantitatively remove bacterial cells from the "wound" surface, and we show that the surface-trapped bacteria are completely killed. The drug delivery function of the composite thus represents an extra safeguarding property and thus probably one of the most important additional advances of a next-generation or smart wound dressing ensuring the complete removal and/or eradication of the pathogen of a freshly infected wound.

Microbiological Findings and Clinical Outcomes in Ugandan Patients with Infected Burn Wounds

Nosocomial wound infections are a dreaded complication in patients with burns. However, access to the necessary microbiological diagnostics is impaired in low-resource settings. This prospective observational cohort study aimed to describe the bacterial pathogens, resistance profiles and clinical outcomes of patients with wound infections admitted to the largest specialized unit for burns and plastic surgery in Uganda. Blood and wound swab cultures were taken for bacterial species identification and antibiotic susceptibility testing. A total of 140 patients (female: n = 62, 44.3%) with a median age of 26 (IQR 7–35) years were included between October 2020 and April 2022, of which the majority (n = 101, 72.2%) had burn wounds (72.3% Grade 2b, 14.9% Grade 3). Gram-negative Enterobacterales, Pseudomonas spp. and Acinetobacter spp. were most commonly isolated from wound swabs and nearly all isolates were multidrug resistant with very limited treatment options. While the clinical outcome was favorable in 21 (15%) study participants, the majority were left with disabilities (minor: n = 41, 29.3%, moderate: n = 52, 37%, major: n = 14 (10%)). Twelve (8.6%) study participants died, mostly of Gram-negative sepsis. Our findings highlight the urgent need for routine access to microbiological diagnostics to improve patient care and local surveillance efforts on antimicrobial resistance.

Molecular characterizations of antibiotic resistance, biofilm formation, and virulence determinants of Pseudomonas aeruginosa isolated from burn wound infection.

Burn injuries result in disruption of the skin barrier against opportunistic infections. Pseudomonas aeruginosa is one of the main infectious agents colonizing burn wounds and making severe infections. Biofilm production and other virulence factors along with antibiotic resistance limit appropriate treatment options and time. Wound samples were collected from hospitalized burn patients. P.aeruginosa isolates and related virulence factors identified by the standard biochemical and molecular methods. Antibiotic resistance patterns were determined by the disc diffusion method and β-lactamase genes were detected by polymerase chain reaction (PCR) assay. To determine the genetic relatedness amongst the isolates, enterobacterial repetitive intergenic consensus (ERIC)-PCR was also performed. Forty P.aeruginosa isolates were identified. All of these isolates were biofilm producers. Carbapenem resistance was detected in 40% of the isolates, and blaTEM (37/5%), blaVIM (30%), and blaCTX-M (20%) were the most common β-lactamase genes. The highest resistance was detected to cefotaxime, ceftazidime, meropenem, imipenem and piperacillin, and 16 (40%) isolates were resistant to these antibiotics. The minimum inhibitory concentrations (MIC) of colistin was lower than 2μg/mL and no resistance was observed. Isolates were categorized to 17 MDR, 13 mono-drug resistance, and 10 susceptible isolates. High genetic diversity was also observed among the isolates (28 ERIC types) and most carbapenem-resistant isolates were classified into four main types. Antibiotic resistance, particularly carbapenem resistance was considerable among the P.aeruginosa isolates colonizing burn wounds. Combining carbapenem resistance with biofilm production and virulence factors would result in severe and difficult-to-treat infections.

Combined Silver Sulfadiazine Nanosuspension with Thermosensitive Hydrogel: An Effective Antibacterial Treatment for Wound Healing in an Animal Model.

Silver sulfadiazine (AgSD) is widely used in burn wound treatment due to its broad-spectrum antibacterial activity. However, its application in wound healing is greatly hindered by the low solubility of AgSD particles and their cellular cytotoxicity. Herein, we studied the safety and in vivo efficacy of nano-sized silver sulfadiazine loaded in poloxamer thermosensitive hydrogel (NS/Gel). In NS/Gel, silver sulfadiazine was prepared into silver sulfadiazine nanosuspension (NS) to improve the solubility and enhance its antibacterial activity, whereas the poloxamer thermosensitive hydrogel was selected as a drug carrier of NS to achieve slow drug release and reduced cytotoxicity. The acute toxicity of silver sulfadiazine nanosuspension was first evaluated in healthy mice, and its median lethal dose (LD50) was calculated by the modified Karber method. Furthermore, in vivo antibacterial effect and wound healing property of NS/Gel were evaluated on the infected deep second-degree burn wound mice model. The mortality ratio of mice was concentration-dependent, and the LD50 for silver sulfadiazine nanosuspension was estimated to be 252.1 mg/kg (230.8 to 275.4 mg/kg, 95% confidence limit). The in vivo dosages used for burn wound treatment (40-50 mg/kg) were far below LD50 (252.1 mg/kg). NS/Gel significantly accelerated wound healing in the deep second wound infection mice model, achieving > 85% wound contraction on day 14. Staphylococcus aureus in the wound region was eradicated after 7 days in NS/Gel group, while the bacterial colony count was still measurable in the control group. Histological analysis and cytokines measurement confirmed that the mice treated with NS/Gel exhibited well-organized epithelium and multiple keratinized cell layers compared to control groups with the modulated expression of IL-6, VEGF, and TGF-β. The combination of silver sulfadiazine nanosuspension and thermo-responsive hydrogel has great potential in clinical burn wound treatment.

Effect of silver-containing hydrofiber dressing on burn wound healing: A meta-analysis and systematic review.

Silver sulfadiazine is commonly used to treat local burn wounds. Aquacel-Ag is a hydrogen fiber dressing containing ionic silver that reduces burn wound infection and promotes antimicrobial activity. It is necessary to compare the efficacy of the two in the healing of burns. The aim of this study was to systematically evaluate the effect of Aquacel-Ag on burn wound healing. A computerized search of CNKI, VIP, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase, Science Direct, Web of Science, Wiley Online Library, and Open Access Library databases was performed from January 1, 2000 to December 31, 2021 for randomized controlled clinical trials. The trials on Aquacel-Ag dressing and silver sulfadiazine in the treatment of burns were selected. Meta-analysis was performed using Review Manager 5.0 software. Eleven articles were finally included, with 794 burn patients. Meta-analysis results showed that compared with patients treated with silver sulfadiazine, burn patients treated with Aquacel-Ag dressing had shorter wound healing time [MD=-2.49, 95% CI (-5.64-0.65), p=0.12], significantly lower tumor necrosis factor-α (TNF-α) level [MD=-0.52, 95% CI (-0.82-0.22), p=0.0008], higher wound healing rate [MD=8.41, 95% CI (3.39-13.43), p=0.001], fewer dressing changes [MD=-3.27, 95% CI (-4.90-1.63), p < 0.0001]. Aquacel-Ag dressing can shorten wound healing time and effectively reduce inflammatory reactions in burn patients compared with silver sulfadiazine, but their safety still needs further exploration and analysis.

Potential antibacterial activity and healing effect of topical administration of bone marrow and adipose mesenchymal stem cells encapsulated in collagen-fibrin hydrogel scaffold on full-thickness burn wound infection caused by Pseudomonas aeruginosa

Burns injuries are prone to hospital-acquired infections, and Pseudomonas aeruginosa is one of the most common causes of mortality and morbidity in patients with burn injuries. Thus, this study aimed to analyze the effects of topical treatment with bone marrow (BM-MSC) and adipose mesenchymal stem cells (AD-MSC) encapsulated in collagen and fibrin scaffolds in a Balb/c model of burn wound infection. Extraction of stem cells from adipose and bone marrow tissue of rats was performed and cells were characterized using standard methods. Then, collagen, fibrin and collagen-fibrin scaffolds were constructed and the extracted cells were encapsulated in all three scaffolds. Then, 3rd degree burn was induced in mice and 1.5 × 108 (CFU/ml) of P. aeruginosa was introduced to the burn wound. Subsequently, after 24 h of inducing wound infection, encapsulated MSCs were introduced as dressings to burn wound infection and microbial load as well as rate of wound infection healing was measured. The results of this study showed that the use of BM-MSC and AD-MSC encapsulated in collagen-fibrin scaffold reduced the bacteria load down to 54 and 21 CFU/gr, respectively (P < 0.05). Moreover, BM-MSC and AD-MSC encapsulated in collagen-fibrin showed 80% and 75% wound healing, respectively (P < 0.05). Also, we found no significant between cell origin and healing. Encapsulation of MSCs into collagen-fibrin scaffolds could be effective not only against P. aeruginosa infection, but also healing and regeneration of burn wound.

3D Printed Chitosan/Alginate Hydrogels for the Controlled Release of Silver Sulfadiazine in Wound Healing Applications: Design, Characterization and Antimicrobial Activity.

The growing demand for personalized medicine requires innovation in drug manufacturing to combine versatility with automation. Here, three-dimensional (3D) printing was explored for the production of chitosan (CH)/alginate (ALG)-based hydrogels intended as active dressings for wound healing. ALG hydrogels were loaded with 0.75% w/v silver sulfadiazine (SSD), selected as a drug model commonly used for the therapeutic treatment of infected burn wounds, and four different 3D CH/ALG architectures were designed to modulate the release of this active compound. CH/ALG constructs were characterized by their water content, elasticity and porosity. ALG hydrogels (Young's modulus 0.582 ± 0.019 Mpa) were statistically different in terms of elasticity compared to CH (Young's modulus 0.365 ± 0.015 Mpa) but very similar in terms of swelling properties (water content in ALG: 93.18 ± 0.88% and in CH: 92.76 ± 1.17%). In vitro SSD release tests were performed by using vertical diffusion Franz cells, and statistically significant different behaviors in terms of the amount and kinetics of drugs released were observed as a function of the construct. Moreover, strong antimicrobial potency (100% of growth inhibition) against Staphylococcus aureus and Pseudomonas aeruginosa was demonstrated depending on the type of construct, offering a proof of concept that 3D printing techniques could be efficiently applied to the production of hydrogels for controlled drug delivery.

The Use of Negative Pressure Wound Therapy in Infected Burn Wounds: Bridging the Gap

The Use of Negative Pressure Wound Therapy in Infected Burn Wounds: Bridging the Gap

Retracted: Nanosilver Dressing in Treating Deep II Degree Burn Wound Infection in Patients with Clinical Studies.

[This retracts the article DOI: 10.1155/2021/3171547.].

ОЦЕНКА ЭФФЕКТИВНОСТИ ЛЕЧЕНИЯ ЭКСПЕРИМЕНТАЛЬНЫХ ОЖОГОВЫХ РАН ПО РЕЗУЛЬТАТАМ ЛАБОРАТОРНЫХ И МОРФОЛОГИЧЕСКИХ ИССЛЕДОВАНИЙ

Purpose of the study: to study the dynamics of laboratory blood parameters, as well as the morphological characteristics of the healing of experimental burn wounds when using bacterial cellulose (BC) wound dressings compared to traditional treatment. Materials and methods. 60 rats of both sexes of the Wistar breed were studied, in which skin burn of the third degree was simulated in the experiment. The animals were divided into 3 groups, of which group 1 included individuals who used BC-based wound dressing (n = 20) in the treatment of burn wounds, in group 2 (n=20) BC plates were used after exposure to a 1% chlorhexidine solution, and in group 3 (comparisons, n=20) treatment was carried out using the traditional method (daily dressings with Levomekol ointment). On the fifth, 10th, 15th, 20th, and 28th days, blood was taken from 5 animals to determine the detailed analysis, the main biochemical constants, and the wound tissue was excised for morphological and morphometric evaluation according to the developed criteria. Results. When analyzing laboratory blood parameters, an increase in hemoglobin level was noted, more pronounced in group 3, which is associated with blood clotting due to experimental burn injury. There is a more significant decrease in platelets in group 3 by the end of the study, which characterizes the process of consumption in the open management of an infected burn wound. In groups 1 and 2, compared with traditional treatment in group 3, differences were noted, consisting in a more effective restoration of hemoglobin levels, a decrease in the level of leukocytes, alanine transaminase, and a decrease in azotemia (p&lt;0,05). According to the morphological and morphometric criteria for the healing of burn wounds on days 20 and 28, in 18 (90%) out of 20 rats of groups 1 and 2, the wounds were at the stage of almost complete epithelialization (criterion 4), while in the comparison group this was noted only in 4 (40 %) out of 10 individuals (p&lt;0,01), and in 60% the wounds were in the stage of initial or moderate epithelialization (criteria 2 and 3).

A multifunctional black phosphorus-based adhesive patch intrinsically induces partial EMT for effective burn wound healing.

The ultimate goal of cutaneous wound healing is to reform a stratified epithelium to restore the normal epidermal barrier, which involves the epithelial-to-mesenchymal transition (EMT) process. However, healing strategies based on EMT induction are immature and ambiguous to date. Excessive induction of EMT may cause fibrosis, hypertrophic scarring, and increased risk of malignancy. Here, we present a new EMT-inducing strategy for eliciting partial EMT to facilitate proper epithelial cell migration. The new EMT-inducing system integrates black phosphorus nanosheets (BPNSs), catechol-modified chitosan (CA-CS), and oxidized dextran (Odex) to engineer an adhesive hydrogel patch (C&BP-Patch) with remarkable efficacy on infectious burn wound healing. The C&BP-Patch can orchestrate key early skin wound healing processes including hemostasis, inflammation, and proliferation, which enable fast partial EMT induction to restore an intact epithelial barrier. The C&BP-Patch acts initially as a high-performance bio-sealant to create a moist and stable microenvironment for EMT. Moreover, the photothermal effects of the C&BP-Patch can eliminate bacteria, accelerate microcirculation and reduce inflammation to maintain a proper EMT. Most importantly, the BPNSs can intrinsically induce partial EMT of epithelial cells via a Snail1-mediated signaling pathway. Therefore, our study proposes a new strategy for effective infectious burn wound healing based on inducing partial EMT.

Pseudomonas aeruginosa PAO1 outer membrane vesicles-diphtheria toxoid conjugate as a vaccine candidate in a murine burn model

Pseudomonas aeruginosa is an opportunistic pathogen considered a common cause of nosocomial infection with high morbidity and mortality in burn patients. Immunoprophylaxis techniques may lower the mortality rate of patients with burn wounds infected by P. aeruginosa; consequently, this may be an efficient strategy to manage infections caused by this bacterium. Several pathogenic Gram-negative bacteria like P. aeruginosa release outer membrane vesicles (OMVs), and structurally OMV consists of several antigenic components capable of generating a wide range of immune responses. Here, we evaluated the immunogenicity and efficacy of P. aeruginosa PA-OMVs (PA-OMVs) conjugated with the diphtheria toxoid (DT) formulated with alum adjuvant (PA-OMVs-DT + adj) in a mice model of burn wound infection. ELISA results showed that in the group of mice immunized with PA-OMVs-DT + adj conjugated, there was a significant increase in specific antibodies titer compared to non-conjugated PA-OMVs or control groups. In addition, the vaccination of mice with PA-OMVs-DT + adj conjugated generated greater protective effectiveness, as seen by lower bacterial loads, and eightfold decreased inflammatory cell infiltration with less tissue damage in the mice burn model compared to the control group. The opsonophagocytic killing results confirmed that humoral immune response might be critical for PA-OMVs mediated protection. These findings suggest that PA-OMV-DT conjugated might be used as a new vaccine against P. aeruginosa in burn wound infection.