Background: Biofilm-associated microbial burden is a major barrier to wound healing and is increasingly difficult to control in the era of antimicrobial resistance. This translational study evaluated the antimicrobial performance and tissue compatibility of a commercially available large-area cold atmospheric plasma (CAP) system (CPTpatch®/CPTcube®; Coldplasmatech GmbH, Greifswald, Germany) across in vitro, porcine, and clinical patient settings. Methods: CAP was tested against seven wound-relevant bacterial species, including multidrug-resistant strains, and the fungus Candida albicans in vitro, in two porcine MRSA-infected deep dermal wound models, and in a clinical service-evaluation cohort of 20 chronic lower-limb wounds in 14 patients; 17 wounds had evaluable longitudinal MolecuLight® (Toronto, ON, Canada) fluorescence series. Results: In vitro, CAP induced rapid multi-log killing across the bacterial panel and showed a marked antifungal effect against C. albicans. In porcine MRSA wounds, CAP reduced bacterial burden versus sham by 1.65, 1.89, and 2.04 log10 CFU/g on Days 4, 8, and 11, equivalent to 97.8%, 98.7%, and 99.1% reductions. In a 72-h post-inoculation MRSA biofilm model, the strongest 5×/week regimen achieved 2.51 log10 (99.69%) and 3.18 log10 (99.93%) reductions versus baseline after 2- and 4-min CAP exposures, respectively. Clinically, twice-weekly CAP was associated with a significant decline in MolecuLight® fluorescence grades over 5 weeks (p < 0.001); effective surface disinfection at 5 weeks was observed in 16/17 evaluable wounds. Conclusions: From bench to bedside, the investigated CAP system delivered rapid broad-spectrum antimicrobial activity, reduced MRSA burden in biofilm-infected porcine wounds, and was associated with clinically measurable suppression of wound surface bioburden while remaining tissue-sparing. These findings support further controlled studies to define clinical benefit in wound care.
This study investigated the efficacy and safety of a novel thermo-reversible antimicrobial wound gel (TRG, revyve Antimicrobial Wound Gel) designed to combat biofilm-related infections in wounds. The TRG was evaluated for its ability to disrupt biofilms, sustain antimicrobial activity and promote wound healing. The gel exhibited thermo-reversible properties, transitioning from a less viscous liquid ≤ 18°C to a highly viscous solid gel at wound temperature which would facilitate easy application and removal. Antimicrobial testing demonstrated that TRG effectively inactivated a broad range of wound-related pathogens, including Staphylococcus aureus and Pseudomonas aeruginosa, with a 99.99%-99.9999% reduction in bacterial counts within 30 min. The TRG also maintained its antimicrobial efficacy after multiple inoculations with high microbial load (107 CFU/mL) over 7 days. In vitro biofilm assays showed effectiveness against biofilm bacteria with a reduction of ≥ 99.99% bacterial counts with one application over the course of 7 days. Biocompatibility testing confirmed that TRG was safe, with no signs of tissue necrosis or signs of tissue damage and no impact on wound healing in a porcine wound model. TRG's ability to reduce both planktonic and biofilm-based bacteria without compromising wound healing makes it a promising candidate for treating both chronic and acute wounds.
Porcine wound models are central to translational cutaneous repair research because porcine skin reproduces many structural and healing features of human skin and supports clinically relevant wound sizes, sampling strategies and device testing. This review summarises the historical development and current use of major porcine wound platforms including incisional, partial-thickness, full-thickness, infected, chronic-like, diabetic, ischaemic, burn, pressure ulcer, hypertrophic scar and radiation models, with emphasis on methodological rigour, translational strengths and study-specific limitations. We further highlight how spatially resolved molecular profiling, longitudinal imaging and integrated transcriptomic datasets are expanding mechanistic interrogation of porcine wounds and may support development of AI-enabled analytic frameworks when linked to well-annotated healing outcomes. Emerging humanised and genetically engineered swine provide additional opportunities to model human-specific immune or comorbidity contexts, although broader validation remains necessary. Key challenges remain the difficulty of sustaining chronicity in otherwise healthy animals, inter-study variability in wound generation and reporting and the need to align preclinical endpoints with clinically meaningful outcomes. Overall, porcine models remain the most clinically relevant large-animal platforms for bridging mechanistic wound-healing studies and late-stage preclinical therapeutic evaluation.
BACKGROUND:Atopic dermatitis (AD) is a skin disorder characterized by reduced skin barrier function, which often leads to recurring infections, predominantly by Staphylococcus aureus and methicillin-resistant S. aureus, that exacerbate disease severity. Managing these infections is made challenging by antibiotic resistance and biofilm formation. Nitric oxide (NO) has emerged as a promising antimicrobial treatment that can disperse biofilm and may provide an alternative treatment for AD infections. METHODS:This study evaluated the antimicrobial efficacy of 3 topical NO-releasing formulations at various concentrations against established MRSA infections, from an AD-derived isolate, in a porcine wound infection model. Partial thickness wounds were inoculated and, after 48 hours of biofilm formation, were treated daily with NO formulations or vehicle control, or left untreated. Wounds were recovered for baseline, day 4, or day 7 bacterial enumeration. RESULTS:All tested NO-releasing formulations substantially reduced MRSA burden compared with baseline counts, and most effectively with the highest concentrations. 20% NO+GEL resulted in a significant reduction of 99.23% compared with baseline at day 7. The 16% NO+UNG treatment, compared with the untreated control, had bacterial reductions on day 4 and day 7 of greater than 99.5%. The greatest reduction of 99.97% (>3 Log CFU/mL) was observed for 6% NO+CREAM compared with the untreated control group at day 7. CONCLUSIONS:NO-releasing treatments have considerable efficacy against MRSA infections and biofilm. These findings support the potential of NO as an antimicrobial treatment for AD patients, and further evaluation should be conducted to assess clinical efficacy.
Over 90% of chronic wounds have biofilm infections, making the need for inhibiting reformation of biofilm post-debridement paramount to support progression through the normal phases of wound healing. Herein, we describe a porcine wound model infected with methicillin-resistant Staphylococcus aureus (MRSA) and examine the ability of an antimicrobial barrier composed of native type I collagen and polyhexamethylene biguanide (PCMP) to serve as a barrier to protect wounds and support progression through the innate wound healing cascade. Wounds were inoculated with MRSA and allowed to form a biofilm for 72 h, subjected to standard of care sharp debridement, then either left untreated or received PCMP for 5, 10, 15 or 20 days. Wounds were assessed for bioburden, wound closure and expression of genes related to wound healing. Wounds treated with PCMP exhibited statistically lower MRSA levels compared to untreated controls and achieved 90% closure by 2 weeks of treatment. Gene expression analysis demonstrated that by reducing bacterial load, wounds progressed through the innate wound healing cascade, while untreated wounds exhibited a dampening of the immune response. Additionally, for randomly assigned wounds, PCMP was not reapplied at dressing changes to assess the impact of inconsistent wound protection. At all timepoints, a resurgence in bioburden was observed following removal of PCMP if the wounds had not fully closed. This study highlights the value of PCMP as an antimicrobial barrier and the importance of protecting wounds through closure and resolution.
INTRODUCTION:Wounds are colonized frequently by heterogeneous microflora. Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) are two of the most isolated bacterial species from wounds, and both typically form highly organized biofilms. Nitric oxide (NO) is a short-lived, diatomic, lipophilic gas with antimicrobial activity. Recently, NO and its derivatives have been shown to exhibit broad-spectrum antimicrobial activity against bacteria, viruses, and parasites. MATERIALS AND METHODS:P. aeruginosa strain ATCC 27312 or military isolate PA09-010 were combined with methicillin-resistant S. aureus strain MRSA USA300 to demonstrate the ability of NO to reduce polymicrobial infections in a porcine wound infection model. Deep partial-thickness wounds (10 mm × 7 mm × 0.5 mm) were made on four animals using a specialized electrokeratome. Wounds were inoculated with MRSA USA300 combined with PA09-010 in three animals and MRSA USA300 combined with PA27312 in one animal, then wounds were covered with polyurethane film dressings. After 48 hours, three wounds were recovered for baseline enumeration. The remaining wounds were randomly assigned to treatment groups and treated once daily. The NO topical gels tested were combinations of two phases, ointment phases with various concentrations (2-20%) combined with hydrogels with fast or slow release kinetics. A 4-day study with microbiological recovery was conducted on day 4. A separate 7-day study was also conducted, with microbial burden assessed on day 7. RESULTS:The largest efficacy against MRSA USA300 was observed for the NO formulation with 2% concentration and fast release kinetics. This treatment reduced the MRSA USA300 bacterial count by more than 99.97% and 99.95% from baseline in wounds co-infected with PA09-010 and PA 27312, respectively, at day 7. Treatments showed a minimal efficacy against PA27312 and PA09-010 strains in both assessment times. MRSA USA300 was reduced to a lesser extent when it was combined with PA27312 as compared to PA09-010. CONCLUSIONS:These studies demonstrate that NO-releasing topical formulations effectively reduce the MRSA burden in established biofilms composed of multiple microorganisms. Minimal efficacy against PA was observed. It has been demonstrated that MRSA bioburden is significantly reduced when inoculated together with P. aeruginosa. A better understanding of mechanisms of host-bacteria interactions, in single or mixed species biofilms, may lead to the development of novel therapeutic approaches. Overall, NO offers a promising alternative treatment against MRSA in polymicrobial infections.
Chronic wounds present a major burden to patients, health care professionals, and health care systems worldwide, yet treatment options remain limited and often ineffective. Although initially promising, growth factor-based therapies displayed limited and underwhelming effectiveness largely due to poor bioavailabilbioity and impaired receptor function within the chronic wound microenvironment. Here we demonstrate that chronic wounds exhibit elevated cholesterol synthesis, which disrupts growth factor signaling by sequestering receptors within lipid rafts. To address this, we developed a novel therapy combining growth factors with cyclodextrin in an ECM-mimetic scaffold, enabling localized cholesterol modulation and improved receptor accessibility. We demonstrate that this approach enhances growth factor bioavailability and functionality, creating a regenerative environment. In both human ex vivo and diabetic mouse wound models, this targeted co-delivery strategy significantly improved healing outcomes by stimulating angiogenesis and re-epithelialization, supporting a promising new direction for chronic wound therapy through localized metabolic modulation of the wound niche.
INTRODUCTION:Nitric oxide (NO) is a lipophilic gas with potent antimicrobial activity. Several in vitro and in vivo studies have demonstrated the broad-spectrum antimicrobial activity of NO-releasing compounds against bacteria, viruses, and parasites. The objective of this study was to assess the efficacy of topical NO formations with sustained release on microbial reduction in wounds. MATERIALS AND METHODS:Swine was used as the preclinical animal model because of the similarities of porcine skin to human skin. Second-degree burn wounds were created in 3 pigs and then inoculated with Methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, or Candida albicans and covered with polyurethane film dressings to create biofilms. After 48 hours, wounds were then treated daily and then recovered for the bacterial burden assessments. Statistical analysis was performed using IBM SPSS statistics 27 using one-way ANOVA. RESULTS:All treatments significantly reduced (P ≤ .05) the bacterial counts between assessment days 4 and 7. Wounds treated with the NVN4000 (1.8%) exhibited greater than 99.7% bacterial reduction on days 4 and 7. Significant differences (P ≤ .05) were observed in wounds treated with NVN4000 (1.8%) compared to silver sulfadiazine. CONCLUSIONS:These studies demonstrate that topical NO-releasing formulations effectively reduce the microbial burden of several microorganisms and exhibit superior antimicrobial efficacy compared to silver sulfadiazine in the porcine wound model.
Background Microorganisms tend to rely on close relationships with other species to survive. Consequently, biofilms formed by interactions of different species have been shown to delay the wound healing process. Studies suggest these mixed-population infections contribute to the development of drug resistance and inhibition of host immune response. Silver sulfadiazine (SSD) has been shown to effectively decrease the risk of infection in an open wound. Typically, these are bacterial wound infections; however, the role of fungal species needs further attention.Objectives The purpose of this in vitro study was to determine the effect of SSD on interactions between Pseudomonas aeruginosa 09-009 (PA1) or P. aeruginosa 09-010 (PA2) and Candida albicans ATTC 64550 (CA).Methods A mixture of 4 mL of tryptic soy broth (TSB) and 100 mu L of CA and/or PA1 or PA2 (similar to 106 log cfu/mL) inoculums were deposited into either wells or vials. The wells or vials were then sonicated (50 W for 10 s) to separate microorganisms attached to the walls. After incubation, cell counts were performed at 24 and 48 h for each microorganism using specific media.Results Our results show that without SSD treatment, P. aeruginosa exhibits an inhibitory effect on C. albicans. Treatment with SSD demonstrated significant reduction of P. aeruginosa; however, C. albicans persisted. This experiment demonstrates that SSD was effective in reducing the bioburden of both P. aeruginosa strains after 24 and 48 h; however, it was not as effective in reducing C. albicans.Conclusions The data suggest that for polymicrobial mixed infections containing Pseudomonas spp. and C. albicans, treatment with SSD may be beneficial but does not provide adequate microorganism eradication. As such, added treatments that provide coverage for Candida infection are necessary. Additional in vivo studies are needed to obtain a better understanding of the complex interactions between these organisms.
BackgroundThe colonization of Staphylococcus aureus (SA) acquired in nosocomial infections may develop acute and chronic infections such as Methicillin-Resistant Staphylococcus aureus (MRSA) in the nose. As a commensal microorganism with the ability to form a biofilm, SA can dwell on the skin, nostrils, throat, perineum, and axillae of healthy humans. Nitric oxide (NO) is an unstable gas with various molecular functions and has antimicrobial properties which are converted into many potential treatments.MethodsMethicillin-Resistant Staphylococcus aureus MRSA BAA1686 isolated from nasal infection was used in a porcine wound infection model. Deep partial-thickness wounds (10mm x 7mm x 0.5mm) were made on three animals using a specialized electrokeratome. All wounds were inoculated and then covered with polyurethane film dressings for biofilm formation. After 48 hours, three wounds were recovered from each animal for baseline enumeration. The remaining wounds were randomly assigned to six treatment groups and treated once daily. The treatment groups are as follows: NO topical ointments concentrations of 0.3, 0.9 and 1.8%, Vehicle Ointment, Mupirocin 2%, and Untreated Control. Microbiological recoveries were conducted on day 4 and day 7.ResultsThe greatest efficacy observed from the NO formulations against MRSA BAA1686 was the 1.8% concentration. This agent was able to reduce more than 99% of bacterial counts when compared to Baseline, Vehicle Ointment, and Untreated Control wounds on both assessment days. Mupirocin 2% was the overall best treatment against MRSA BAA1686 on both assessment days, with a significant reduction (p ≤ 0.05) of 4.70 ± 0.13 Log CFU/mL from day 4 to day 7.ConclusionsOverall, the positive control Mupirocin 2% was the most effective in eliminating MRSA BAA1686 throughout the study. This experiment demonstrated a downward trend from the highest concentration of NO topical ointment formulations to the lowest concentrations on both assessment days (0.3% - 1.8%). Out of all NO topical ointments, the highest concentration (1.8%) was the most effective with the potential to be an alternative treatment against a MRSA nasal strain biofilm.
ABSTRACT Introduction Debridement plays a critical role in wound management. In addition to removing necrotic tissue, debridement can eliminate bacteria frequently harbored within the tissue. This study evaluated a novel debridement method that uses plasma-based radiofrequency technology to remove tissue and bacteria. Coblation is a technology that uses radiofrequency energy to excite the electrolytes in a conductive medium, such as saline, to create a precisely focused plasma. This plasma field contains highly energized particles that possess sufficient energy to break tissue molecular bonds, causing the tissue to dissolve at relatively low temperatures (typically 40 °C to 70 °C). Materials and Methods Eighteen deep dermal wounds measuring 22 mm × 22 mm × 3 mm deep were created on pigs. Wounds were inoculated with methicillin-resistant Staphylococcus aureus USA300 (MRSA USA300) in combination with shrapnel and then covered with a polyurethane dressing for 24 hours. Wounds were then randomly assigned to one of the 3 treatment groups: (1) Coblation, (2) surgical debridement, and (3) no debridement. Wounds were biopsied on days 0, 5, 9, and 12, and specimens were processed for MRSA counts using selective media. Statistical analysis was performed using IBM SPSS statistics 27 using one-way ANOVA. Results Comparison between coblation and surgical debridement showed a decrease in bacterial count in all assessment times. The lowest bacterial count in all assessment times was observed in wounds debrided with coblation showing a statistically significant (P ≤ .05) decrease in more than 2 Log CFU/g on days 0, 5, and 9 compared to no debridement. On day 12, coblation-debrided wounds exhibited 6.10 ± 0.22 Log CFU/g, and this value represents 99.99% of reduction compared with non-debrided wounds (P ≤ .05). More than 96% of reduction (P ≤ .05) resulted in wounds treated with coblation compared with surgically debrided. Conclusions Reducing MRSA bacterial infection counts, especially of biofilm-associated organisms, in combination with shrapnel may have important clinical implications, especially for the military personnel. Further research into the use of this technology in wound management is warranted.
Chronic non-healing wounds pose significant challenges due to an elevated inflammatory response caused in part by bacterial contamination (Physiol Rev. 2019;99:665). These wounds lead to billions being spent in the health care system worldwide (N Engl J Med. 2017;376:2367, Int J Pharm. 2014;463:119). We studied the in-vitro and in-vivo antimicrobial effects of a multimodal wound matrix (MWM) against two common wound pathogens, Methicillin-Resistant Staphylococcus aureus (MRSA USA300) and Pseudomonas aeruginosa ATCC 27312 (PA27312) (Int Wound J. 2019;16:634). The in-vitro study conducted was a zone of inhibition test with the two microbes at 104 Log CFU/mL inoculated on Tryptic soy agar with 5% sheep blood (TSAII) plates. Treatments used were MWM, Mupirocin (Positive control for MRSA), Silver Sulfadiazine (Positive Control for PA), Petrolatum and Sterile Saline (both serving as Negative Controls). Treatments were allowed to diffuse into the agar for 3 h and then were incubated for 24 h at 37°C. The in-vivo study utilized a deep dermal porcine wound model (22 × 22 × 3 mm) created on six animals. Three animals were inoculated with MRSA USA300 and the other three with PA27312 with each allowing a 72-h biofilm formation. After 72 h, baseline wounds were assessed for bacterial concentration and all remaining wounds were treated with either MWM alone, Silver Treatment or Untreated Control. Wounds were assessed on days 4, 8 and 12 after treatment application for microbiological analysis. In-vitro, MWM exhibited significant inhibition of MRSA USA300 and PA27312 growth when compared to negative controls (p ≤ 0.05). Likewise, in-vivo, the MWM-treated wounds exhibited a significant (p ≤ 0.05) bacterial reduction compared to all other treatment groups, especially on days 8 and 12 for both pathogens. MWM demonstrated promise in addressing colonized wounds with biofilms. Additional studies on MWM's benefits and comparisons with existing treatments are warranted to optimize wound care strategies (Adv Wound Care. 2021;10:281).
Owing to the increasingly high volume of cutaneous and percutaneous procedures performed annually, the demand for local anesthesia has steadily risen. The gold-standard formulations for local anesthesia contain epinephrine at a concentration of 1:100,000 added to lidocaine to aid in hemostasis. Epinephrine, an α-agonist, also exhibits off-target β-adrenergic effects that carry risk of adverse events with these injections. Furthermore, the ongoing global shortage of epinephrine highlights the need for a safer and viable alternative. Midodrine, a targeted a1-adrenergic receptor agonist, is utilized as a vasopressor to induce arterial and venous vasoconstriction. We developed a formulation of 2% lidocaine combined with 1:2,000,000 epinephrine and 50 μM midodrine (midodrine/lidocaine/epinephrine formulation), hypothesizing that this combination would exhibit synergism on hemostasis. In a porcine model of blood loss after punch biopsies, our formulation was compared with 2% lidocaine; 2% lidocaine with 1:100,000 epinephrine; 2% lidocaine with 1:2,000,000 epinephrine; and 2% lidocaine with 50 μM midodrine. Our results indicate that 2% lidocaine with 1:100,000 epinephrine and our midodrine/lidocaine/epinephrine formulation were statistically comparable, with both significantly reducing bleeding when compared with the 2% lidocaine (P < .05). The 2% lidocaine with midodrine alone also showed additional promise as an effective hemostatic formulation. Thus, combination of low-concentration epinephrine and midodrine with lidocaine may exhibit synergistic hemostatic effect in cutaneous surgical settings while reducing potential off-target effects of either vasoconstrictor alone at higher concentrations as adjunct monotherapies.
Third-degree burns typically result in pronounced scarring and contraction in superficial and deep tissues. Established techniques such as debridement and grafting provide benefit in the acute phase of burn therapy, nevertheless, scar and contraction remain a challenge in deep burns management. Our ambition is to evaluate the effectiveness of novel cell-based therapies, which can be implemented into the standard of care debridement and grafting procedures. Twenty-seven third-degree burn wounds were created on the dorsal area of Red Duroc pig. After 72 h, burns are surgically debrided using a Weck knife. Split-thickness skin grafts (STSGs) were then taken after debridement and placed on burn scars combined with bone marrow stem cells (BM-MSCs). Biopsy samples were taken on days 17, 21, and 45 posttreatment for evaluation. Histological analysis revealed that untreated control scars at 17 days are more raised than burns treated with STSGs alone and/or STSGs with BM-MSCs. Wounds treated with skin grafts plus BM-MSCs appeared thinner and longer, indicative of reduced contraction. qPCR revealed some elevation of α-SMA expression at day 21 and Collagen Iα2 in cells derived from wounds treated with skin grafts alone compared to wounds treated with STSGs + BM-MSCs. We observed a reduction level of TGFβ-1 expression at days 17, 21, and 45 in cells derived from wounds treated compared to controls. These results, where the combined use of stem cells and skin grafts stimulate healing and reduce contraction following third-degree burn injury, have a potential as a novel therapy in the clinic.
A new recombinant proteolytic enzyme, isolated from maggot saliva, with fibrinolytic action has been investigated through a series of non-clinical toxicology and in-vitro/in-vivo pharmacology studies to explore its potential safety and efficacy as an enzymatic debridement agent for use in chronic wounds. Studies indicate that the enzyme has a good safety profile. When locally administered, it is not detrimental to wound healing, is non-sensitising and is rapidly inactivated in the systemic circulation. Adverse effects are limited, at very high concentrations, to transient erythema at the site of application. In-vitro testing indicates that the enzyme, whilst selective for fibrin, has additional proteolytic action against collagen and elastin, with enzymatic action for all three substrates being dose dependent. In-vivo, we used an established MRSA biofilm model, in which microbiological counts were used as a surrogate for debridement efficacy. Here, we showed that higher concentrations of the enzyme in a formulated proprietary gel, significantly reduced MRSA counts over a period of 2 to 14 days, and significantly improved the vascularity of the wound at 14 days. Together, these data support the potential for this maggot-derived proteolytic enzyme as a clinically effective debriding agent.
Common carp ( Cyprinus carpio ) are a serious invasive species of riverine habitats in Australia and several control measures have been proposed. The strategy and potential success of any control measure will be influenced by carp population dynamics. Carp survival and distribution are driven by abiotic environmental factors (e.g., water flow rates and habitat availability), which vary greatly in space and time in Australian river systems. To inform realistic control strategies, we developed a mechanistic (process-based) carp metapopulation model with parameters explicitly linked to spatio-temporal estimates of habitat suitability. To demonstrate the use of this model, we evaluated how recovery times following a one-time management action (that results in population reduction) varied across five river catchments in the Murray-Darling Basin (MDB), eastern Australia, using reconstructed environmental conditions from the early 1990s to 2016. We found that recovery time at the catchment scale can be highly dependent on the flood-drought cycle, with recovery varying from to 2 to 10 years between wet and dry periods. In more stable catchments, however, ~ 6 years (range 4–8 years) is more likely. Our results are consistent with the paradigm that carp are a highly successful invasive species, with strong recovery potential, especially during periods of access to quality nursery habitat (i.e., during floodplain and wetland inundation).
OBJECTIVE The purpose of this study was to use an in vivo biofilm porcine model to examine a new polyvinyl alcohol-based gelling fibre dressing with silver and compare it to other commercial dressings containing: polyvinyl alcohol-based gelling fibre without silver; carboxymethyl cellulose-based fibre with silver, benzethonium chloride and ethylenediaminetetraacetic acid; and untreated control. METHODS A total of 52 deep partial-thickness wounds (10x7x0.5mm) were created on each of three animals and inoculated with 25µl of meticillin-resistant Staphylococcus aureus (MRSA) (106 colony forming units (CFU)/ml). Wounds were covered for 24 hours to allow biofilm formation and were randomly designated to one of the four treatments. Samples were recovered for microbiological and histological analysis on days 3, 5 and 7 post-treatment. RESULTS Polyvinyl alcohol-based gelling fibre dressing with silver was able to significantly reduce biofilm more effectively than the other treatment groups. By day 7, wounds treated with the dressing had a 2.72±0.01 log CFU/g reduction in MRSA count versus untreated control wounds and a 2.59±0.01 log CFU/g reduction versus baseline counts. For histology analysis, all wounds reached 100% re-epithelialisation by day 5. CONCLUSION The results of this study indicated that polyvinyl alcohol-based gelling fibre dressing with silver was effective against biofilm of antibiotic-resistant staphylococcal strains without inhibiting the wound healing process, and may have important clinical implications when treating acute and/or hard-to-heal wounds.
Large datasets of phosphorylation interactions are constantly being generated, but deciphering the complex network structure hidden in these datasets remains challenging. Many phosphorylation interactions occurring in human cells have been identified and constitute the basis for the known phosphorylation interaction network. We overlayed onto this network phosphorylation datasets obtained from an antibody microarray approach aimed at determining changes in phospho-signalling of host erythrocytes, during infection with the malaria parasite Plasmodium falciparum. We designed a pathway analysis tool denoted MAPPINGS that uses random walks to identify chains of phosphorylation events occurring much more or much less frequently than expected. MAPPINGS highlights pathways of phosphorylation that work synergistically, providing a rapid interpretation of the most critical pathways in each dataset. MAPPINGS confirmed several signalling interactions previously shown to be modulated by infection, and revealed additional interactions which could form the basis of numerous future studies. The MAPPINGS analysis strategy described here is widely applicable to comparative phosphorylation datasets in any context, such as response of cells to infection, treatment, or comparison between differentiation stages of any cellular population.