Development, characterization, and evaluation of a simple polymicrobial colony biofilm model for testing of antimicrobial wound dressings.

Chronic wound infections are generally of polymicrobial nature with aerobic and anaerobic bacteria, as well as fungi frequently observed in them. Wound treatment involves a series of steps, including debridement of the wound, flushing, and often the use of multiple wound dressings many of which are antimicrobial. Yet, many wound dressings are tested versus single species of planktonic microbes, which fails to mirror the real-life presence of biofilms. AIMS: Simple biofilm models are the first step to testing of any antimicrobial and wound dressing; therefore, the aim of this study was to develop and validate a simple polymicrobial colony biofilm wound model comprised of Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans on RPMI-1640 agar. The model was then used to evaluate the topical disinfectant chlorohexidine and four commercially available wound dressings using the polymicrobial model. The model used was as a starting point to mimic debridement in clinical care of wounds and the effectiveness of wound dressings evaluated afterwards. METHODS AND RESULTS: Planktonic assessment using AATCC100-2004 demonstrated that all antimicrobial wound dressings reduced the planktonic microbial burden below the limit of detection; however, when challenged with polymicrobial colony biofilms, silver wound dressings showed limited effectiveness (1-2 log CFU reductions). In contrast, a single iodine releasing wound dressing showed potent antibiofilm activity reducing all species CFUs below the limit of detection (>6-10 log) depending on the species. A disrupted biofilm model challenge was performed to represent the debridement of a wound and wound silver-based wound dressings were found to be marginally more effective than in whole colony biofilm challenges while the iodine containing wound dressing reduced microbial recovery below the limit of detection. CONCLUSIONS: In this model, silver dressings were ineffective versus the whole colony biofilms but showed some recovery of activity versus the disrupted colony biofilm. The iodine wound dressing reduced the viability of all species below the level of detection. This suggests that mode of action of wound dressing should be considered for the type of biofilm challenge as should the clinical use, e.g. debridement.

NIR-responsive CN-Pt-GEM hydrogel induces necroptosis and immunotherapeutic responses prevent postoperative recurrence and wound infection in lung carcinoma.

BACKGROUND: Cancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection is an important component of successful surgery. With the development of new nanotechnology, more treatment options have been provided for postoperative adjuvant therapy. This study presents an innovative hydrogel system that stimulates tumoricidal immunity after surgical resection of non-small cell lung cancer (NSCLC) and prevents cancer relapse. RESULTS: The hydrogel system is based on the excellent photothermal conversion performance of single-atom platinum (CN-Pt) along with the delivery and release of the chemotherapy drug, gemcitabine (GEM). The system is coated onto the wound surface after tumor removal with subsequent near-infrared (NIR) photothermal therapy, which efficiently induces necroptosis of residual cancer cells, amplifies the levels of damage-associated molecular patterns (DAMPs), and increases the number of M1 macrophages. The significantly higher levels of phagocytic macrophages enhance tumor immunogenicity and sensitize cancer cells to CD8 + T-cell immunity to control postoperative recurrence, which has been verified using an animal model of postoperative lung cancer recurrence. The CN-Pt-GEM-hydrogel with NIR can also inhibit postoperative wound infection. CONCLUSIONS: These findings introduce an alternative strategy for supplementing antitumor immunity in patients undergoing resection of NSCLC tumors. The CN-Pt-GEM-hydrogel with the NIR system also exhibits good biosafety and may be adaptable for clinical application in relation to tumor resection surgery, wound tissue filling, infection prevention, and recurrence prevention.

Effective antibacterial agents in modern wound dressings: a review.

Wound infections are a significant concern in healthcare, leading to long healing times. Traditional approaches for managing wound infections rely heavily on systemic antibiotics, which are associated with the emergence of antibiotic-resistant bacteria. Therefore, the development of alternative antibacterial materials for wound care has gained considerable attention. In today's world, new generations of wound dressing are commonly used to heal wounds. These new dressings keep the wound and the area around it moist to improve wound healing. However, this moist environment can also foster an environment that is favorable for the growth of bacteria. Excessive antibiotic use poses a significant threat to human health and causes bacterial resistance, so new-generation wound dressings must be designed and developed to reduce the risk of infection. Wound dressings using antimicrobial compounds minimize wound bacterial colonization, making them the best way to avoid open wound infection. We aim to provide readers with a comprehensive understanding of the latest advancements in antibacterial materials for wound management.

Improving outcomes for patients with hard-to-heal wounds following adoption of the Wound Hygiene Protocol: real-world evidence.

OBJECTIVE: To evaluate the impact of a four-step biofilm-based wound care strategy, Wound Hygiene Protocol (WHP: cleanse, debride, refashion, and dress), on hard-to-heal wounds. METHOD: This was a prospective, real-world analysis of hard-to-heal wounds managed with the WHP that incorporated Aquacel Ag+ (Convatec Ltd., UK) dressings. Data were captured electronically between April 2021 and December 2022. The primary endpoint was change in wound volume from baseline to final assessment. RESULTS: A total of 693 wounds in 669 patients (median patient age: 74 years) were included in the analysis with a median treatment time of 31 days. Most health professionals were general nurses (50%) or nurse practitioners (38%). Patient homes (27%) and community clinics (27%) were the most common clinical settings. Venous leg ulcers (26%) and pressure ulcers/injuries (17%) were the most common wound type. Duration was >12 months in 21% of wounds. At baseline, the mean wound volume was 57.8cm3. At the final assessment, mean wound volume was 17.2cm3, corresponding to an 80% reduction from baseline; p<0.001). At baseline, 66% of wounds were static or deteriorating. At final assessment, this had decreased to 5%, and 94% had improved or healed. Exudate levels were moderate or high in 69% of wounds at baseline which decreased to 25% at final assessment (p<0.001). Suspected biofilm and local wound infection decreased from 79% and 43%, respectively, at baseline, to 18% and 3%, respectively, at final assessment (p<0.001 for both). CONCLUSION: The WHP is a new proposed standard of care that successfully treated hard-to-heal wounds by addressing the key local barriers to wound healing.

Fifteen-minute consultation: Management of mammalian bites in children-from local wound care to prophylactic antibiotics.

Animal and human bites are a common reason for emergency consultation, especially in children. The most common complication of bite wounds is local infection. Systemic infections are much rarer. The key in reducing the risk of infection after a mammalian bite is local wound management with either primary or delayed closure. The benefit of administering prophylactic antibiotics is controversial.In this review, we provide a summary of the current evidence for the management of mammalian bites in children, including recommendations for appropriate investigations, wound management, administration of prophylactic and therapeutic antibiotics and the prevention of systemic infections.

LL37 Microspheres Loaded on Activated Carbon-chitosan Hydrogel: Anti-bacterial and Anti-toxin Wound Dressing for Chronic Wound Infections.

Antimicrobial peptide LL37 is a promising antibacterial candidate due to its potent antimicrobial activity with no known bacterial resistance. However, intrinsically LL37 is susceptible to degradation in wound fluids limits its effectiveness. Bacterial toxins which are released after cell lysis are found to hinder wound healing. To address these challenges, encapsulating LL37 in microspheres (MS) and loading the MS onto activated carbon (AC)-chitosan (CS) hydrogel. This advanced wound dressing not only protects LL37 from degradation but also targets bacterial toxins, aiding in the healing of chronic wound infections. First, LL37 MS and LL37-AC-CS hydrogel were prepared and characterised in terms of physicochemical properties, drug release, and peptide-polymer compatibility. Antibacterial and antibiofilm activity, bacterial toxin elimination, cell migration, and cell cytotoxicity activities were investigated. LL37-AC-CS hydrogel was effective against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. LL37-AC-CS hydrogel bound more endotoxin than AC with CS hydrogel alone. The hydrogel also induced cell migration after 72 h and showed no cytotoxicity towards NHDF after 72 h of treatment. In conclusion, the LL37-AC-CS hydrogel was shown to be a stable, non-toxic advanced wound dressing method with enhanced antimicrobial and antitoxin activity, and it can potentially be applied to chronic wound infections to accelerate wound healing.

Does the use of DACC-coated dressings improve clinical outcomes for hard to heal wounds: A systematic review.

Reports of overuse and antimicrobial resistance have fuelled some clinicians to adopt alternative wound dressings termed to be non-medicated or non-antimicrobials, which still claim antimicrobial or antibacterial activity. In this PROSPERO-registered systematic review, we evaluated the in vivo clinical evidence for the effectiveness of DACC-coated dressings in chronic, hard to heal wound-related outcomes. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Framework was adopted as the template in constructing this systematic review. The PICO format (Population [or patients], Intervention, Comparison [control], Outcome/s) was used to identify key clinical questions in determining patient outcomes under two domains (infection control and wound healing). A systematic search was performed in PubMed, OVID, Cochrane Library, clinical trial registries and data sources from independent committees. Abstracts of all studies were screened independently by two reviewers, with six further reviewers independently assessing records proceeding to full review. The authors rated the quality of evidence for each of the outcomes critical to decision making. After excluding duplicates, 748 records were screened from the databases, and 13 records were sought for full review. After full review, we excluded a further three records, leaving ten records for data extraction. Three records were narrative reviews, three systematic reviews, two prospective non-comparative before/after studies, one prospective head-to-head comparator cohort study and one retrospective head-to-head comparator cohort study. No RCTs or case versus control studies were identified. The overall quality of clinical evidence for the use of DACC-coated dressing to improve wound infection and wound healing outcomes was assessed as very low. There is an urgent unmet need to perform appropriately designed RCTs or case-control studies. The extracted data provide no clarity and have limited to no evidence to support that using a DACC-coated dressing improves wound infection or wound healing outcomes. Further, there is no evidence to suggest this therapy is either superior to standard of wound care or equivocal to topical antimicrobial agents in the management of infected hard to heal wounds.

In vitro prevention and inactivation of biofilms using controlled-release iodine foam dressings for wound healing.

Microbial biofilms are a major hindrance in the wound healing process, prolonging the inflammatory response phase, thus making them a target in treatment. The aim of this study is to assess the antibacterial properties of commercially available wound dressings, of various material composition and antibacterial agents, towards multiple in vitro microbial and biofilm models. A variety of in vitro microbial and biofilm models were utilised to evaluate the ability of wound dressing materials to sequester microbes, prevent dissemination and manage bioburden. Sequestering and dissemination models were used to evaluate the ability of wound dressing materials to prevent the biofilm-forming bacterium, Pseudomonas aeruginosa, from migrating through dressing materials over a 24-72 h challenge period. Additionally, Centre for Disease Control (CDC) Bioreactor and Drip Flow models were used to evaluate antibacterial killing efficacy towards established P. aeruginosa and Staphylococcus aureus biofilms using more challenging, wound-like models. Controlled-release iodine foam and silver-impregnated carboxymethylcellulose (CMC) wound dressing materials demonstrated potent biofilm management properties in comparison to a methylene blue and gentian violet-containing foam dressing. Both the iodine-containing foam and silver-impregnated CMC materials effectively prevented viable P. aeruginosa dissemination for up to 72 h. In addition, the controlled-release iodine foam and silver-impregnated CMC materials reduced P. aeruginosa bioburden in the Drip Flow model. The controlled-release iodine foam demonstrated superiority in the CDC Bioreactor model, as both the silver- and iodine-containing materials reduced S. aureus to the limit of detection, but P. aeruginosa growth was only completely reduced by controlled-release iodine foam dressing materials. The data generated within the in vitro biofilm models supports the clinical data available in the public domain for the implementation of iodine foam dressings for effective biofilm management and control in wound care.

The impact of ulinastatin on wound infection and healing in patients with burn wounds: A meta-analysis.

Burn injuries result in localised tissue damage and precipitate systemic responses; routine clinical treatments, which typically include metabolic nutritional support and anti-infection therapies, do not yield optimal outcomes. Therefore, we aimed to systematically evaluate the effects of ulinastatin on wound infection and healing in patients with burns to provide reliable evidence-based recommendations for burn treatment. An electronic search of the Web of Science, PubMed, Cochrane Library, Embase, Wanfang, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure databases, supplemented by manual searches, was conducted from database inception to October 2023 to collect randomised controlled trials (RCTs) assessing the efficacy of ulinastatin for the treatment of burns. Two researchers screened all retrieved articles according to the inclusion and exclusion criteria; the included studies were evaluated for quality, and the relevant data were extracted. Stata 17.0 software was employed for data analysis. Overall, 8 RCTs with 803 patients were included, with 404 and 399 in the ulinastatin and conventional treatment groups, respectively. The analysis revealed that wound infections (odds ratio [OR] = 0.08, 95% CI: 0.02-0.35, p = 0.001) and complications (OR = 0.21, 95% CI: 0.10-0.42, p < 0.001) were significantly lower, and wound healing time (standardised mean differences [SMD] = -1.31, 95% CI: -2.05 to -0.57, p = 0.001) was significantly shorter, in the ulinastatin groups than in the control group. This meta-analysis revealed that ulinastatin can effectively reduce the incidence of wound infections and complications and significantly shorten the duration of wound healing in patients with burns, thereby promoting early recovery in these patients.

Using the Galleria mellonella burn wound and infection model to identify and characterize potential wound probiotics.

Burn wound infection is the leading cause of mortality among burn wound patients. One of the most commonly isolated bacterial burn wound pathogens is Pseudomonas aeruginosa, a notorious nosocomial multidrug-resistant pathogen. As a consequence of its recalcitrance to frontline antibiotic therapy, there is an urgent need to develop alternative treatment avenues to tackle this pathogen. One potential alternative infection prevention measure is to seed the wound bed with probiotic bacteria. Several species of Lactobacillus, a common commensal bacterium, have been previously reported to display growth inhibition activity against wound pathogens. Various species of this genus have also been shown to augment the wound healing process, which makes it a promising potential therapeutic agent. Due to the complexity of the burn wound trauma and burn wound infection, an in vivo model is required for the development of novel therapeutics. There are multiple in vivo models that are currently available, the most common among them being the murine model. However, mammalian burn wound infection models are logistically challenging, do not lend themselves to screening approaches and come with significant concerns around ethics and animal welfare. Recently, an invertebrate burn wound and infection model using G. mellonella has been established. This model addresses several of the challenges of more advanced animal models, such as affordability, maintenance and reduced ethical concerns. This study validates the capacity of this model to screen for potential wound probiotics by demonstrating that a variety of Lactobacillus spp. can limit P. aeruginosa burn wound infection and improve survival.

Activity of a hypochlorous acid-producing electrochemical bandage as assessed with a porcine explant biofilm model.

The activity of a hypochlorous acid-producing electrochemical bandage (e-bandage) in preventing methicillin-resistant Staphylococcus aureus infection (MRSA) infection and removing biofilms formed by MRSA was assessed using a porcine explant biofilm model. e-Bandages inhibited S. aureus infection (p = 0.029) after 12 h (h) of exposure and reduced 3-day biofilm viable cell counts after 6, 12, and 24 h exposures (p = 0.029). Needle-type microelectrodes were used to assess HOCl concentrations in explant tissue as a result of e-bandage treatment; toxicity associated with e-bandage treatment was evaluated. HOCl concentrations in infected and uninfected explant tissue varied between 30 and 80 µM, decreasing with increasing distance from the e-bandage. Eukaryotic cell viability was reduced by an average of 71% and 65% in fresh and day 3-old explants, respectively, when compared to explants exposed to nonpolarized e-bandages. HOCl e-bandages are a promising technology that can be further developed as an antibiotic-free treatment for wound biofilm infections.

Using tap water compared with normal saline for cleansing wounds in adults: a literature review of the evidence.

OBJECTIVE: The aim of this literature review was to establish the evidence for using tap water as opposed to normal saline for cleansing wounds in adults. Tap water is widely available and non-toxic to wounds, making it a cost-effective solution for wound cleansing. Despite that, contrary opinions exist with regard to its safety, such as: fear of wound colonisation by Pseudomonas spp. found in plumbing systems of healthcare facilities; damage to the wound bed; or increased pain when tap water is used for wound cleansing. METHOD: A PICO model was used as a guide to form the title, and the standards for inclusion and exclusion of studies were prespecified to form the eligibility criteria. The search was conducted using a range of databases, including CINAHL, MEDLINE, PubMed and Cochrane Central Register of Controlled Trials. RESULTS: Included were seven studies: five randomised controlled trials (RCTs), a quasi-RCT and a cross-sectional study. Of these, six studies demonstrated that use of tap water had no significant influence on wound infection rates when compared to normal saline; four studies established no adverse results or benefits when using tap water or normal saline for wound cleansing; and one study demonstrated that tap water did not increase wound contamination. Also, one study reported no impact on wound healing when tap water or normal saline were used for cleansing; four established that tap water was cost-effective compared to normal saline; and one demonstrated increased patient satisfaction when tap water was used for wound irrigation. CONCLUSION: Current evidence supports tap water as a safe and cost-effective solution for wound cleansing.

Effect of topical antibiotics on the prevention and management of wound infections: A meta-analysis.

A meta-analysis research was implemented to appraise the effect of topical antibiotics (TAs) on the prevention and management of wound infections (WIs). Inclusive literature research was performed until April 2023, and 765 interconnected researches were reviewed. The 11 selected researches included 6500 persons with uncomplicated wounds at the starting point of the research: 2724 of them were utilising TAs, 3318 were utilising placebo and 458 were utilising antiseptics. Odds ratio (OR) and 95% confidence intervals (CIs) were utilised to appraise the consequence of TAs on the prevention and management of WIs by the dichotomous approach and a fixed or random model. TAs had significantly lower WI compared with placebo (OR, 0.59; 95% CI, 0.38-0.92, p = 0.02) and compared with antiseptics (OR, 0.52; 95% CI, 0.31-0.88, p = 0.01) in persons with uncomplicated wounds (UWs). TAs had significantly lower WIs compared with placebo and antiseptics in persons with UWs. However, caution needs to be taken when interacting with their values because of the low sample size of some of the chosen researches and low number of researches found for the comparisons in the meta-analysis.

[Expert consensus on emergency open wound irrigation].

Wound irrigation is one of the most effective means to prevent open wound infection after injury. Wound irrigation can reduce the risk of wound infection and promote wound healing by removing the cell fragments, surface bacteria, dressings residues, residual foreign body and wound exudates loosely attached to the wound. The effect of wound irrigation mainly depends on the pressure of irrigation, the direction of fluid flow, the type of liquid, temperature and volume/amount of irrigation fluid. In response to the phenomenon that emergency open wounds are not irrigated in a standardized manner in China, the Posttraumatic Special Infections and Biting Injury Study Group of the Trauma Surgeons Branch of the Chinese Medical Doctor Association and the Animal Injury Treatment Branch of China Association for Disaster and Emergency Rescue Medicine organized domestic experts in the fields of emergency department and trauma treatment centers to collect the latest clinical evidence of emergency open wound irrigation, and wrote this consensus with reference to relevant guidelines, consensus and the clinical experience of Chinese experts. The consensus summarized the important factors affecting wound irrigation and put forward 10 recommendations to improve the knowledge and skills of trauma emergency medical personnel in wound irrigation.

In Vitro Antibiofilm Activity of Hydrogen Peroxide-Generating Electrochemical Bandage against Yeast Biofilms.

Wound infections are caused by bacteria and/or fungi. The presence of fungal biofilms in wound beds presents a unique challenge, as fungal biofilms may be difficult to eradicate. The goal of this work was to assess the in vitro antibiofilm activity of an H2O2-producing electrochemical bandage (e-bandage) against 15 yeast isolates representing commonly encountered species. Time-dependent decreases in viable biofilm CFU counts of all isolates tested were observed, resulting in no visible colonies with 48 h of exposure by plate culture. Fluorescence microscopic analysis showed extensive cell membrane damage of biofilm cells after e-bandage treatment. Reductions in intracellular ATP levels of yeast biofilm cells were recorded post e-bandage treatment. These results suggest that exposure to H2O2-producing e-bandages reduces in vitro viable cell counts of yeast biofilms, making this a potential new topical treatment approach for fungal wound infections.

Water for wound cleansing.

BACKGROUND: Although various solutions have been recommended for cleansing wounds, normal saline is favoured as it is an isotonic solution and is not thought to interfere with the normal healing process. Tap water is commonly used in community settings for cleansing wounds because it is easily accessible, efficient and cost-effective; however, there is an unresolved debate about its use. OBJECTIVES: To assess the effects of water for wound cleansing. SEARCH METHODS: For this fifth update, in May 2021 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that assessed wound cleansing using different types of water (e.g. tap water, distilled, boiled) compared with no cleansing or with other solutions (e.g. normal saline). For this update, we excluded quasi-RCTs, thereby removing some studies which had been included in the previous version of the review. DATA COLLECTION AND ANALYSIS: Two review authors independently carried out trial selection, data extraction and GRADE assessment of the certainty of evidence. MAIN RESULTS: We included 13 trials in this update including a total of 2504 participants ranging in age from two to 95 years. Participants in the trials experienced open fractures, surgical wounds, traumatic wounds, anal fissures and chronic wounds. The trials were conducted in six different countries with the majority conducted in India and the USA. Three trials involving 148 participants compared cleansing with tap water with no cleansing. Eight trials involving 2204 participants assessed cleansing with tap water compared with cleansing with normal saline. Two trials involving 152 participants assessed cleansing with distilled water compared with cleansing with normal saline.  One trial involving 51 participants also assessed cleansing with cooled boiled water compared with cleansing with normal saline, and cleansing with distilled water compared with cleansing with cooled boiled water. Wound infection: no trials reported on wound infection for the comparison cleansing with tap water versus no cleansing. For all wounds, eight trials found the effect of cleansing with tap water compared with normal saline is uncertain (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.59 to 1.19); very low-certainty evidence. Two trials comparing the use of distilled water with normal saline for cleansing open fractures found that the effect on the number of fractures that were infected is uncertain (RR 0.70, 95% CI 0.45 to 1.09); very low-certainty evidence. One trial compared the use of cooled boiled water with normal saline for cleansing open fractures and found that the effect on the number of fractures infected is uncertain (RR 0.83, 95% CI 0.37 to 1.87); very low-certainty evidence. This trial also compared the use of distilled water with cooled boiled water and found that the effect on the number of fractures infected is uncertain (RR 0.59, 95% CI 0.24 to 1.47); very low-certainty evidence. Wound healing: results from three trials comparing the use of tap water with no wound cleansing demonstrated there may be little or no difference in the number of wounds that did not heal between the groups (RR 1.04, 95% CI 0.95 to 1.14); low-certainty evidence. The effect of tap water compared with normal saline is uncertain; two trials were pooled (RR 0.57, 95% CI 0.30 to 1.07) but the certainty of the evidence is very low. Results from one study comparing the use of distilled water with normal saline for cleansing open fractures found that there may be little or no difference in the number of fractures that healed (RR could not be estimated, all wounds healed); the certainty of the evidence is low. Reduction in wound size: the effect of cleansing with tap water compared with normal saline on wound size reduction is uncertain (RR 0.97, 95% CI 0.56 to 1.68); the certainty of the evidence is very low. Rate of wound healing: the effect of cleansing with tap water compared with normal saline on wound healing rate is uncertain (mean difference (MD) -3.06, 95% CI -6.70 to 0.58); the certainty of the evidence is very low. COSTS: two trials reported cost analyses but the cost-effectiveness of tap water compared with the use of normal saline is uncertain; the certainty of the evidence is very low. Pain: results from one study comparing the use of tap water with no cleansing for acute and chronic wounds showed that there may be little or no difference in pain scores. The certainty of the evidence is low. Patient satisfaction: results from one study comparing the use of tap water with no cleansing for acute and chronic wounds showed that there may be little or no difference in patient satisfaction. The certainty of evidence is low. The effect of cleansing with tap water compared with normal saline is uncertain as the certainty of the evidence is very low. AUTHORS' CONCLUSIONS: All the evidence identified in the review was low or very low certainty. Cleansing with tap water may make little or no difference to wound healing compared with no cleansing; there are no data relating to the impact on wound infection. The effects of cleansing with tap water, cooled boiled water or distilled water compared with cleansing with saline are uncertain, as is the effect of distilled water compared with cooled boiled water. Data for other outcomes are limited across all the comparisons considered and are either uncertain or suggest that there may be little or no difference in the outcome.

Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host-defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6-deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.

Antiseptic versus non-antiseptic solutions for preventing infection in acute traumatic wounds: a systematic review.

OBJECTIVE: To compare the effectiveness of antiseptic solutions to that of non-antiseptic solutions in reducing wound infection rate, reducing bacterial load and improving wound healing. METHOD: We searched PubMed MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), ProQuest Medical Database and medRxiv for randomised controlled trials (RCTs) comparing antiseptic solutions with non-antiseptic solutions in simple, uncomplicated acute traumatic wounds. Qualitative data synthesis was employed. Risk of bias was assessed and GRADE assessment was used to evaluate quality of evidence. RESULTS: In this systematic review, four studies with a total of 875 participants were included, of which two studies showed a significant reduction of wound infection rate using povidone-iodine (p=0.001 and p=0.03). The use of non-antiseptic solutions significantly increased bacterial load on acute traumatic wounds (p=0.0001). The quality of evidence was very low. No studies reported on wound healing outcome. CONCLUSION: No robust conclusions can be implemented in clinical practice. Future studies are needed to compare the use of antiseptic and non-antiseptic solutions in acute traumatic wounds.

Significant and rapid reduction of free endotoxin using a dialkylcarbamoyl chloride-coated wound dressing.

OBJECTIVE: Endotoxin causes inflammation and can impair wound healing. Conventional methods that reduce bioburden in wounds by killing microorganisms using antibiotics, topical antimicrobials or antimicrobial dressings may induce endotoxin release from Gram-negative bacteria. Another approach is to reduce bioburden by adsorbing microorganisms, without killing them, using dialkylcarbamoyl chloride (DACC)-coated wound dressings. This study evaluated the endotoxin-binding ability of a DACC-coated wound dressing (Sorbact Compress, Abigo Medical AB, Sweden) in vitro, including its effect on the level of natural endotoxin released from Gram-negative bacteria. METHOD: Different concentrations of purified Pseudomonas aeruginosa endotoxin and a DACC-coated dressing were incubated at 37°C for various durations. After incubation, the dressing was removed and endotoxin concentration in the solution was quantified using a Limulus amebocyte lysate (LAL) assay. The DACC-coated dressing was also incubated with Pseudomonas aeruginosa cells for one hour at 37°C. After incubation, the dressing and bacterial cells were removed and shed endotoxin remaining in the solution was quantified. RESULTS: Overnight incubation of the DACC-coated wound dressing with various concentrations of purified Pseudomonas aeruginosa endotoxin (96-11000 EU/ml) consistently and significantly reduced levels of free endotoxin by 93-99% (p<0.0001). A significant endotoxin reduction of 39% (p<0.001) was observed after five minutes. The DACC-coated dressing incubated with clinically relevant Pseudomonas aeruginosa cells also reduced shed endotoxin by >99.95% (p<0.0001). CONCLUSION: In this study, we showed that a DACC-coated wound dressing efficiently and rapidly binds both purified and shed endotoxin from Pseudomonas aeruginosa in vitro. This ability to remove both endotoxin and bacterial cells could promote the wound healing process.

Gelatin Hydrogels Loaded with Lactoferrin-Functionalized Bio-Nanosilver as a Potential Antibacterial and Anti-Biofilm Dressing for Infected Wounds: Synthesis, Characterization, and Deciphering of Cytotoxicity.

Gelatin hydrogels are attractive for wound applications owing to their well-defined structural, physical, and chemical properties as well as good cell adhesion and biocompatibility. This study aimed to develop gelatin hydrogels incorporated with bio-nanosilver functionalized with lactoferrin (Ag-LTF) as a dual-antimicrobial action dressing, to be used in treating infected wounds. The hydrogels were cross-linked using genipin prior to loading with Ag-LTF and characterized for their physical and swelling properties, rheology, polymer and actives interactions, and in vitro release of the actives. The hydrogel's anti-biofilm and antibacterial performances against S. aureus and P. aeruginosa as well as their cytotoxicity effects were assessed in vitro, including primary wound healing gene expression of human dermal fibroblasts (HDFs). The formulated hydrogels showed adequate release of AgNPs and LTF, with promising antimicrobial effects against both bacterial strains. The Ag-LTF-loaded hydrogel did not significantly interfere with the normal cellular functions as no alteration was detected for cell viability, migration rate, and expression of the target genes, suggesting the nontoxicity of Ag-LTF as well as the hydrogels. In conclusion, Ag-LTF-loaded genipin-cross-linked gelatin hydrogel was successfully synthesized as a new approach for fighting biofilms in infected wounds, which may be applied to accelerate healing of chronic wounds.