Recently, biomaterials have been increasingly used for burn wound healing, but burn wound infections and biomaterial-associated infections still need to be addressed. As a novel inorganic antimicrobial, the antimicrobial effect of gallium nitrate was investigated, and the minimum inhibitory concentration (MIC) of gallium nitrate against bacteria that are common in infected burn wounds was determined with a Microbial Viability Assay Kit-WST. The results showed that the MIC of Ga(NO 3 ) 3 against E. coli and E.faecalis was 256 mg mL À1, and it was 512 mg mL À1 against P. aeruginosa, K. pneumonia, E. cloacae, A.baumannii, S. maltophilia, S. aureus and S. epidermidis. Meanwhile, transmission electron microscopy (TEM) found similar visual evidence of the mechanism by which the gallium ion attacks both Gramnegative and Gram-positive bacteria, which was in agreement with the MIC results. By TEM observation, it was found that detachment of the cell membrane and wall and the appearance of an electron-light region containing condensed substances occurred in both Ga 3+ -treated E. coli and Ga 3+ -treated S.aureus cells, with smaller morphological changes in Ga 3+ -treated S. aureus compared with E. coli. This research shows the effective and wide-spectrum antimicrobial properties of gallium nitrate against most bacteria encountered in burn wound infections. Gallium(III) could be a good choice when fighting an infected burn wound, and it is a promising candidate for modifying biomaterials or medical devices to prevent infection in burn wounds.
Improving the efficacy of existing antibiotics is a promising strategy for combating antibiotic-resistant/tolerant bacterial pathogens that have become a severe threat to human health. We previously reported that aminoglycoside antibiotics could be dramatically potentiated against stationary-phase Escherichia coli cells under hypoionic shock conditions (i.e., treatment with ion-free solutions), but the underlying molecular mechanism remains unknown. Here we show that mechanosensitive (MS) channels, a ubiquitous protein family sensing mechanical forces of cell membrane, mediate such hypoionic shock-induced aminoglycoside potentiation. Two-minute treatment under conditions of hypoionic shock (e.g., in pure water) greatly enhances the bactericidal effects of aminoglycosides against both spontaneous and triggered E. coli persisters, numerous strains of Gram-negative pathogens in vitro , and Pseudomonas aeruginosa in mice. Such potentiation is achieved by hypoionic shock-enhanced bacterial uptake of aminoglycosides and is linked to hypoionic shock-induced destabilization of the cytoplasmic membrane in E. coli . Genetic and biochemical analyses reveal that MscS-family channels directly and redundantly mediate aminoglycoside uptake upon hypoionic shock and thus potentiation, with MscL channel showing reduced effect. Molecular docking and site-directed mutagenesis analyses reveal a putative streptomycin-binding pocket in MscS, critical for streptomycin uptake and potentiation. These results suggest that hypoionic shock treatment destabilizes the cytoplasmic membrane and thus changes the membrane tension, which immediately activates MS channels that are able to effectively transport aminoglycosides into the cytoplasm for downstream killing. Our findings reveal the biological effects of hypoionic shock on bacteria and can help to develop novel adjuvants for aminoglycoside potentiation to combat bacterial pathogens via activating MS channels.
Effective coverage and protection is a priority in wound treatment. Collagen and chitosan have been widely used for wound dressings due to their excellent biological activity and biocompatibility. Silver nanoparticles (AgNPs) have a powerful antibacterial effect. In this study, a macromolecular and small-molecular collagen mixed solution, a macromolecular and small-molecular chitosan mixed solution were prepared, and a silver nanoparticle-loaded collagen-chitosan dressing (AgNP-CCD) has been proposed. First, the effects of a collagen-chitosan mixed solution on the proliferation of human umbilical vein endothelial cells and the secretion of cytokines were evaluated. Then, the characteristics and antibacterial effects of the AgNP-CCD were tested, and the effects on wound healing and the influence of wound cytokine expression were investigated via a deep second-degree burn wound model. The results showed that at the proper proportion and concentration, the collagen-chitosan mixed solution effectively promoted cell proliferation and regulated the levels of growth factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF], platelet-derived growth factor [PDGF], transforming growth factor [TGF-β1], basic fibroblastic growth factor [bFGF]) and inflammatory factors (TNF-α, IL-1β, IL-6, IL-8). Moreover, AgNP solutions at lower concentrations exerted limited inhibitory effects on cell proliferation and had no effect on cytokine secretion. The AgNP-CCD demonstrated satisfactory morphological and physical properties as well as efficient antibacterial activities. An in vivo evaluation indicated that AgNP-CCD could accelerate the healing process of deep second-degree burn wounds and played an important role in the regulation of growth and inflammatory factors, including VEGF, EGFL-7, TGF-β1, bFGF, TNF-α and IL-1β. This AgNP-CCD exerted excellent biological effects on wound healing promotion and cytokine expression regulation.
Background: Hyperfibrinolysis and pro/anti-inflammatory imbalance usually occur in the early stage of severe burns. Soluble urokinase-type plasminogen activator receptor (suPAR) is involved in fibrinolysis and inflammation. To date, the levels of circulating suPAR in non-survivors with severe burns remain unknown. This study aimed to investigate the early association between circulating suPAR levels and biomarkers of fibrinolysis, pro/anti-inflammatory, and prognosis. Methods: Sixty-four consecutive Chinese patients with severe burns and 26 healthy volunteers were enrolled in a prospective observational cohort. Clinical characteristics and laboratory data were collected prospectively. Blood samples were collected at 48 h post-burn, and suPAR and biomarkers of pro/anti-inflammatory and fibrinolysis were detected by enzyme-linked immunosorbent assays. Important indicators between non-survivors and survivors were compared. Linear regression analysis was performed to screen variables associated with suPAR. Logistic regression analysis and receiver operating characteristic curve (ROC) analysis were performed to evaluate the prognostic value of suPAR. Result: Compared with the control group, the circulating suPAR levels in the survivors (P < 0.001) and non-survivors (P ¼ 0.017) were higher. Compared with survivors, non-survivors had lower circulating suPAR levels at 48 h post-burn, and they showed a higher degree of fibrinolysis (higher D-dimer) and a lower TNF-a/IL-10 ratio. According to linear regression analysis, the variables independently associated with a lower suPAR level were lower platelet factor 4 (PF-4), urokinase-type plasminogen activator (uPA), and TNF-a/IL-10 levels and a higher D-dimer level. Logistic regression and ROC analyses indicated that a suPAR level 4.70 mg/L was independently associated with 30-day mortality. Conclusion: Low circulating suPAR levels at 48 h post-burn in severe burn patients may reflect decreased TNF-a/IL-10 ratio and increased hyperfibrinolysis. suPAR can predict 30-day mortality in patients with severe burn. KEYWORDS-Burn, hyperfibrinolysis, IL-10, pro/anti-inflammatory imbalance, suPAR ABBREVIATIONS-ABSI score-abbreviated burn severity index score; APTT-activated partial prothrombin time; AUCarea under the curve; CRP-C-reactive protein; IFN-g-interferon g; IL-interleukin; INR-international standardized ratio; ns-no significance; PAI-1-plasminogen activator inhibitor-1; PF-4-platelet factor 4; PT-prothrombin time; ROCreceiver operating characteristic curve; SOFA-sequential organ failure assessment; sP-selectin-soluble P-selectin; suPAR-soluble urokinase-type plasminogen activator receptor; TBSA-total burn surface area; TNF-a-tumor necrosis factor a; TT-thrombin time; uPA-urokinase-type plasminogen activator
Negative pressure wound therapy with instillation (NPWTi) has the dual function of negative pressure sealing drainage and irrigation, which overcomes the disadvantages of NPWT, such as tube obstruction, inability to apply topical medicine, and poor anti-infection ability. NPWTi has been researched extensively and widely used in various types of wounds, and certain effects have been achieved. A series of parameters for NPWTi have not been unified at present, including the flushing fluid option, flushing mode, and treatment period. This paper reviews the research progress of these parameters for NPWTi and their application in the treatment of orthopaedic wounds.instillation, negative pressure wound therapy, orthopaedic wounds, treatment parameters Key Messages• NPWTi has the dual function of negative pressure sealing drainage and irrigation • setting of treatment parameters for NPWTi has not been unified yet: further research studies are required • although there are multiple choices of instillation solutions, normal saline is recommended as the first choice; the recommended setting is the intermittent instillation mode and À125 to 150 mmHg, the duration time depends on the type of wound • NPWTi has been widely used in all kinds of wounds in orthopaedics, such as acute or chronic infected wounds, osteomyelitis, soft tissue injuries, and surgical wound management
ObjectiveThis study aims to explore the clinical effect of early rehabilitation training combined with negative pressure wound therapy (NPWT) for treating deep partial-thickness hand burns.MethodsTwenty patients with deep partial-thickness hand burns were randomly divided into an experimental group (n = 10) and a control group (n = 10). In the experimental group, early rehabilitation training combined with NPWT was performed, including the proper sealing of the negative pressure device, intraoperative plastic brace, early postoperative exercise therapy during negative pressure treatment, and intraoperative and postoperative body positioning. Routine NPWT was conducted in the control group. Both groups received 4 weeks of rehabilitation after wounds healed by NPWT with or without skin grafts. Hand function was evaluated after wound healing and 4 weeks after rehabilitation, including hand joint total active motion (TAM) and the brief Michigan Hand Questionnaire (bMHQ).ResultsTwenty patients were involved in this study, including 16 men and 4 women, aged 18–70 years, and the hand burn area ranged from 0.5% to 2% of the total body surface area (TBSA). There was no significant difference in TAM and bMHQ scores between the two groups after negative pressure removal. After 4 weeks of rehabilitation training, the TAM scores and bMHQ scores were significantly improved in both groups (p < 0.05); among them, those of the experimental group were both significantly better than those of the control group (p < 0.05).ConclusionThe application of early rehabilitation training combined with NPWT to treat deep partial-thickness hand burns can effectively improve hand function.
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