Antimicrobial Wound Dressings Research Articles

Advances of antimicrobial dressings loaded with antimicrobial agents in infected wounds.

Wound healing is a complex process that is critical for maintaining the barrier function of the skin. However, when a large quantity of microorganisms invade damaged skin for an extended period, they can cause local and systemic inflammatory responses. If left untreated, this condition may lead to chronic infected wounds. Infected wounds significantly escalate wound management costs worldwide and impose a substantial burden on patients and healthcare systems. Recent clinical trial results suggest that the utilization of effective antimicrobial wound dressing could represent the simplest and most cost-effective strategy for treating infected wounds, but there has hitherto been no comprehensive evaluation reported on the efficacy of antimicrobial wound dressings in promoting wound healing. Therefore, this review aims to systematically summarize the various types of antimicrobial wound dressings and the current research on antimicrobial agents, thereby providing new insights for the innovative treatment of infected wounds.

Advances in ionic liquid-based antimicrobial wound healing platforms.

Wound infections, marked by the proliferation of microorganisms at surgical sites, necessitate the development of innovative wound dressings with potent bactericidal properties to curb microbial growth and prevent bacterial infiltration. This study explores the recent strides in utilizing ionic liquid-based polymers as highly promising antimicrobial agents for advanced wound healing applications. Specifically, cationic polymers containing quaternary ammonium, imidazolium, guanidinium, pyridinium, triazolium, or phosphonium groups have emerged as exceptionally effective antimicrobial compounds. Their mechanism of action involves disrupting bacterial membranes, thereby preventing the development of resistance and minimizing toxicity to mammalian cells. This comprehensive review not only elucidates the intricate dynamics of the skin's immune response and the various stages of wound healing but also delves into the synthesis methodologies of ionic liquid-based polymers. By spotlighting the practical applications of antimicrobial wound dressings, particularly those incorporating ionic liquid-based materials, this review aims to lay the groundwork for future research endeavors in this burgeoning field. Through a nuanced examination of these advancements, this article seeks to contribute to the ongoing progress in developing cutting-edge wound healing platforms that can effectively address the challenges posed by microbial infections in surgical wounds.

Effect of Poly(Vinyl Pyrrolidone) on Iodine Release from Acrylate-Endcapped Urethane-Based Poly(Ethylene Glycol) Hydrogels as Antibacterial Wound Dressing.

Infections are still a major cause of morbidity in burn wounds. Although silver has been used strongly in past centuries as an anti-bacterial, it can lead to allergic reactions, bacterial resistance, and delayed wound healing. Iodine-based antibacterials are becoming an interesting alternative. In this work, the effect of complexation with poly(vinyl pyrrolidone) (PVP) and poly(ethylene oxide) (PEO)-based polymers is explored by using different acrylate-endcapped urethane-based poly(ethylene glycol) (AUP) polymers, varying the molar mass (MM) of the poly(ethylene glycol) (PEG) backbone, with possible addition of PVP. The higher MM AUP outperforms the swelling potential of commercial wound dressings such as Kaltostat, Aquacel Ag, and Hydrosorb and all MM show superior mechanical properties. The addition of iodine to the polymers is compared to Iso-Betadine Tulle (IBT). Interestingly, the addition of PVP does not lead to increased iodine complexation compared to the blank AUP polymers, while all have a prolonged iodine release compared to the IBT, which leads to a burst release. The observed prolonged release also leads to larger inhibition zones during antibacterial tests. Complexing iodine in AUP polymers with or without PVP leads to antimicrobial wound dressings which may hold potential for future application to treat infected wounds.

Sterilized Polyhexanide-Releasing Chitosan Membranes with Potential for Use in Antimicrobial Wound Dressings.

Wound infection is a common complication of chronic wounds. It can impair healing, which may not occur without external help. Antimicrobial dressings (AMDs) are a type of external help to infected chronic wounds. In this study, highly porous membranes made of only chitosan and containing the antiseptic polyhexanide (poly(hexamethylene biguanide); PHMB) were prepared by cryogelation, aiming to be used in AMDs. These membranes exhibited a water swelling capacity of 748%, a water drop penetration time of 11 s in a dry membrane and a water vapor transmission rate of 34,400 g H2O/m2/24 h when in contact with water. The best drug loading method involved simultaneous loading by soaking in a PHMB solution and sterilization by autoclaving, resulting in sterilized, drug-loaded membranes. When these membranes and a commercial PHMB-releasing AMD were assayed under the same conditions, albeit far from the in vivo conditions, their drug release kinetics were comparable, releasing PHMB for ca. 6 and 4 h, respectively. These membranes exhibited high antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are bacterial species commonly found in infected wounds and blood clotting activity. The obtained results suggest that these membranes may have potential for use in the development of AMDs.

Imperfect cross-linking of xanthan for pH-responsive bio-based composite moist wound dressings by stencil printing.

The work addresses the use of bio-based and -degradable materials for the production of a moist, adaptive and anti-microbial wound dressing. The dressing is targeted to exhibit a pH-dependent active agent release. Xanthan hydrogel structures are coated on cellulose fabrics via stencil printing and subsequently cross-linked using glyoxal. By alteration of the cross-linker content from 1 to 6% by mass, the hydrogel elasticity can be tuned within a range of 2-16kPa storage modulus. Increasing initial glyoxal concentrations also result in higher amounts of glyoxal release. Glyoxal, an anti-microbial agent with approval in veterinary medicine, is mostly released upon wound application supporting infection management. As wound simulation, normal saline, as pH 5 and pH 8 buffer solutions, were used. The release profile and magnitude of approx. 65%-90% glyoxal is pH-dependent. Increased release rates of glyoxal are present in pH 8 fluids, which mostly base on faster hydrogel swelling. Higher total glyoxal release is present in pH 5 fluid and normal saline after 3days. Accordingly, a pH-dependent release profile was encountered. As glyoxal attacks any cell unselectively, it is expected to be effective against antibiotic resistant bacteria. By stencil printing the dressing size can be adjusted to minimize healthy glyoxal tissue exposure.

Recent Trends in Electrospun Antibacterial Nanofibers for Chronic Wound Management

Abstract: Chronic wounds and lesions have a severe impact on the socioeconomic status and compliance of patients all over the world. Diabetes-related chronic, non-healing lesions may necessitate amputation of the damaged limb or organ. These skin lesions are susceptible to microorganisms that cause infections that impede the healing process. Despite the advances in medication development and sophisticated formulations, treating persistent wound infections remains difficult. Electrospun antimicrobial wound dressings offer considerable potential for lowering the risk of infection and accelerating the healing of chronic wounds. Electrospinning is a cost-effective, reproducible, simple, and multifaceted technique for encapsulating hydrophobic and hydrophilic therapeutic molecules within polymeric carriers with wide-ranging applications. In this review, we have discussed extensively the recent advances in electrospun nanofiber formulation techniques for use as wound dressings, as well as the entrapment of various antibacterial biomolecules, such as synthetic antibiotics, phytoconstituents, and metal nanoparticles, which have been embedded into the electrospun nano-fibers, highlighting bioactive antibacterial agents capable of enhancing wound healing. In addition, we focus on the challenges currently being faced in the area of biomedicine as well as the opportunities for electrospinning-based nanomaterials.

Encapsulating Antibiotic and Protein-Stabilized Nanosilver into Sandwich-Structured Electrospun Nanofibrous Scaffolds for MRSA-Infected Wound Treatment.

With the increasing prevalence of microbial infections, which results in prolonged inflammation and delayed wound healing, the development of effective and safe antimicrobial wound dressings of multiple properties remains challenging for public health. Despite their various formats, the available developed dressings with limited functions may not fulfill the diverse demands involved in the complex wound healing process. In this study, multifunctional sandwich-structured electrospinning nanofiber membranes (ENMs) were fabricated. According to the structural composition, the obtained ENMs included a hydrophilic inner layer loaded with curcumin and gentamicin sulfate, an antibacterial middle layer consisting of bovine serum albumin stabilized silver oxide nanoparticles, and a hydrophobic outer layer. The prepared sandwich-structured ENMs (SNM) exhibited good biocompatibility and killing efficacy on Escherichia coli, Staphylococcus aureus, and Methicillin-resistant S. aureus (MRSA). In particular, transcriptomic analysis revealed that SNM inactivated MRSA by inhibiting its carbohydrate and energy metabolism and reduced the bacterial resistance by downregulating mecA. In the animal experiment, SNM showed improved wound healing efficiency by reducing the bacterial load and inflammation. Moreover, 16S rDNA sequencing results indicated that SNM treatment may accelerate wound healing without observed influence on the normal skin flora. Therefore, the constructed sandwich-structured ENMs exhibited promising potential as dressings to deal with the infected wound management.

Real-time in vivo monitoring of the antimicrobial action of combination therapies in the management of infected topical wounds

The increasing prevalence of non-healing infected wounds has become a serious concern in the clinical practice, being associated to population aging and to the rising prevalence of several chronic conditions such as diabetes. Herein, the evaluation of the bactericidal and antibiofilm effects of the natural antiseptic terpenes thymol and farnesol standing alone or in combination with the standard care antiseptic chlorhexidine was carried out both in vitro and in vivo. The in vitro combinatorial treatment of chlorhexidine associated with those terpenes against Staphylococcus aureus in its planktonic and sessile forms demonstrated a superior antibacterial activity than that of chlorhexidine alone. Real-time in vivo monitoring of infection progression and antimicrobial treatment outcomes were evaluated using the bioluminescent S. aureus strain Xen36. In vivo studies on infected wound splinting murine models corroborated the superior bactericidal effects of the combinatorial treatments here proposed. Moreover, the encapsulation of thymol in electrospun Eudragit® S100 (i.e., a synthetic anionic copolymer of methacrylic acid and ethyl acrylate)-based wound dressings was also carried out in order to design efficient antimicrobial wound dressings.

A Sensor for Monitoring the Antimicrobial Activity of Wound Dressings for Both Surgical Site Infections (SSIs) and Chronic Wounds.

Antimicrobial impregnated wound dressings are a critical tool for the management, prevention, and control of surgical site infections (SSIs) and infected chronic wounds. However, the sustained therapeutic antimicrobial activity of the dressing when employed for extended periods cannot be readily determined in vivo. Consequently, dressings are changed frequently to ensure that their antimicrobial activity is maintained. Whilst frequent dressing changes allow the wound to be assessed, this is time-consuming and can cause disruption to the wound bed impairing the healing process. Furthermore, this increases medical costs for the patient and hospitals. This paper introduces a novel concept to monitor the therapeutic levels of an antimicrobial component within a wound dressing ensuring the wound dressing remains "fit for purpose" and avoiding indiscriminate use of antiseptics. This could help to inform clinicians whether the antimicrobial is still being delivered at therapeutic levels and as such when to change the dressing ensuring timely positive clinical outcomes. Silver has been used historically as an antimicrobial agent and is ubiquitous in current generations of antimicrobial wound dressings. However, its activity is complex due to the poor solubility of silver ions in the presence of chloride and the effect of complexation by other components in the dressing and wound ecosystem, not least by serum proteins. In this paper, we detail an electrochemical silver sensor (5D patent protected - WO2023275553A1), constructed using a platinum (Pt) nanoband array electrode, and characterise its response to silver ions. This is determined in the presence of bovine serum albumin (BSA) and simulated wound fluid (SWF) containing chloride and rationalised using atomic analysis of the composition of the SWF. The sensor response in SWF is compared with the antimicrobial activity of silver against Pseudomonas aeruginosa in the planktonic and biofilm state, as a function of the amount of silver nitrate added. At low concentrations, silver in SWF has good solubility but reduced antimicrobial effect due to binding of silver by BSA as shown by the sensor response. At intermediate concentrations, above 10ppm, the silver was efficacious on both planktonic microorganisms and biofilm impregnated with microorganisms and readily detected with the sensor. At high concentrations, silver precipitates and both the silver in solution and the sensor response plateaus. The data demonstrates how the sensor correlates with the antimicrobial activity of the silver in vitro and how this could be used to actively monitor antimicrobials in vivo.

Antimicrobial Wound Dressings: A Concise Review for Clinicians.

Wound management represents a substantial clinical challenge due to the growing incidence of chronic skin wounds resulting from venous insufficiency, diabetes, and obesity, along with acute injuries and surgical wounds. The risk of infection, a key impediment to healing and a driver of increased morbidity and mortality, is a primary concern in wound care. Recently, antimicrobial dressings have emerged as a promising approach for bioburden control and wound healing. The selection of a suitable antimicrobial dressing depends on various parameters, including cost, wound type, local microbial burden and the location and condition of the wound. This review covers the different types of antimicrobial dressings, their modes of action, advantages, and drawbacks, thereby providing clinicians with the knowledge to optimize wound management.

Antimicrobial Wound Dressings based on Bacterial Cellulose and Independently Loaded with Nutmeg and Fir Needle Essential Oils.

The aim of the present study was to obtain antimicrobial dressings from bacterial cellulose loaded with nutmeg and of fir needle essential oils. The attractive properties of BC, such as biocompatibility, good physicochemical and mechanical stability, and high water absorption, led to the choice of this material to be used as a support. Essential oils have been added to provide antimicrobial properties to these dressings. The results confirmed the presence of oils in the structure of the bacterial cellulose membrane and the ability of the materials to inhibit the adhesion of Staphylococcus aureus and Escherichia coli. By performing antibacterial tests on membranes loaded with fir needle essential oil, we demonstrated the ability of these membranes to inhibit bacterial adhesion to the substrate. The samples loaded with nutmeg essential oil exhibited the ability to inhibit the adhesion of bacteria to the surface of the materials, with the 5% sample showing a significant decrease. The binding of essential oils to the membrane was confirmed by thermal analysis and infrared characterization.

Review on applications of Pullulan in bone tissue engineering: Blends and composites with natural and synthetic polymers

Pullulan (PUL) has a diverse range of applicationsdue to its many therapeutic benefits, including biodegradability, biocompatibility, nontoxicity, antimicrobial activity, and adsorption. They are combined with chitosan, polyvinyl pyrrolidone (PVP), polycaprolactone (PCL), heparin, fluorescent polystyrene nanoparticles (PS-NPs), and carboxyl Pullulan to develop properties such as thermal stability, mechanical properties, pH resistance, chemical stability, toughness. The effects of Pullulan content on the properties of the solution, as well as the morphology of the resultant nanofibers, were investigated >80%. The concept of a scaffold can be a useful notion to improve the mechanical behavior of hydrogel-based scaffolds. Compositional analysis by Differential scanning calorimetry (DSC) revealed that Pullulan might enhance the mechanical properties of the nanofibers. This review focuses on the combination and analysis of Pullulan blends and composites of natural and synthetic polymers, as well as their capability in biomedical fields and bone tissue engineering, for example in drug delivery, insulin delivery, food industry, medicinal and biomedical applications, antimicrobial wound dressings, cancer cell targeting, anticancer vaccine improvement, new biopolymer development, food product development and sensing. The electro spinning procedure and the materials employed in it will be covered in this review. The use of Pullulan electrospun nanofibers structures in tissue engineering will also be covered in this paper. The benefits, restrictions, and future opinions were studied. This is because of Pullulan-based polymers have a variety of properties.

Synthesis and characterization of antibacterial self-healable biopolyurethanes with eugenol-based bio-polyol

In this study, antibacterial self-healable polyurethanes (EBPUs series) were prepared using eugenol-based bio-polyol (EBP), which was synthesized by thiol–ene reaction between eugenol and 1,2-ethanedithiol. The effects of EBP content on the mechanical, self-healing, and antibacterial properties of polyurethanes were investigated. When EBP was added into the EBPUs series as a polyol, the tensile strength, elongation at break, and self-healing efficiency values increased to 21.78 MPa, 1462.27%, and 77.85 %, respectively. EBPU−10 shows self-healing efficiency, where its first and second self-healing efficiency reached 76.6 % and 66.1 %, respectively. For antibacterial properties, the EBPUs series show promising antibacterial activity. EBPU−10 inhibited Staphylococcus aureus growth by 99.3 %, and Bacillus cereus growth by 95.7 %, and it inhibited Escherichia coli growth by 82.3 % at 6 h, compared to EBPU−01. Biofilm mass on foams was reduced by EBPU-10, and the morphology of biofilm bacteria was altered, such as their size being reduced, distorted, shrunken, and ruptured. In conclusion, it can be used for various applications, such as packaging, antimicrobial wound dressing, catheter, tissue adhesive, and surgical implant.

Multifunctional chitosan/carbon dots/sodium alginate/zinc oxide double-layer sponge hydrogel with high antibacterial, mechanical and hemostatic properties

Due to the fact that bacterial contamination of wounds is the cause of increased morbidity and mortality today, various antimicrobial wound dressings are developing to prevent wound contamination. In addition, an ideal wound dressing should have proper mechanical and hemostatic properties to maintain wound healing conditions. Here, a double-layer sponge hydrogel nanocomposite wound dressing was designed and manufactured by combining zinc oxide nanoparticles (ZnONPs) with different concentrations in the hydrogel layer and green carbon dots in the sponge layer. The surface morphology of two layers was investigated using a scanning electron microscope. X-ray diffraction proved the presence of ZnONPs. Physical tests showed a decrease in water absorption and water vapor transmission rate and an increase in blood absorption in the presence of ZnO. The sponge layer showed suitable absorption support in the presence of carbon dots. By combining nanoparticles in both layers, the mechanical properties were greatly enhanced. The sponge hydrogel with the highest concentration of ZnO showed excellent inhibition of 41 mm against Pseudomonas aeruginosa bacteria and 25 mm of inhibition against Staphylococcus aureus. Finally, in vitro blood clotting and animal tests confirmed the increase in the hemostatic power of the sponge hydrogel with the maximum concentration of ZnO.

Preclinical performance testing of medical devices with antimicrobial effects

Infections associated with medical device use can have serious consequences for patients. Such healthcare-associated infections are often challenging to treat because of the persistence of microbial biofilms and the presence of antimicrobial-resistant microorganisms. The risks of device-associated infections can be reduced by using medical devices with antimicrobial effects. In this Review, we discuss preclinical performance testing of medical devices with antimicrobial effects, including in vitro strategies, animal models and computational modelling. We examine the clinical performance of antimicrobial bone cements, urinary catheters, venous catheters and wound dressings. Rational preclinical test strategies are needed to obtain information to estimate how well a device will benefit the patient in clinical use. We outline the potential of ex vivo models, microphysiological systems, organoids and medical devices-on-chips as complementary testing strategies. To move preclinical tests from the bench to the bedside, we propose a systems approach to address the many interrelated aspects of medical device interactions using a question-based rubric. The implementation or insertion of medical devices into the body can lead to infections and inflammation, which are often challenging to treat because of the presence of microbial biofilms and antimicrobial-resistant microorganisms. This Review outlines preclinical testing strategies for medical devices with antimicrobial properties to avoid and reduce medical-device-associated infections.

Wound Dressing Modifications for Accelerated Healing of Infected Wounds.

Infections that occur during wound healing involve the most frequent complications in the field of wound care which not only inhibit the whole process but also lead to non-healing wound formation. The diversity of the skin microbiota and the wound microenvironment can favor the occurrence of skin infections, contributing to an increased level of morbidity and even mortality. As a consequence, immediate effective treatment is required to prevent such pathological conditions. Antimicrobial agents loaded into wound dressings have turned out to be a great option to reduce wound colonization and improve the healing process. In this review paper, the influence of bacterial infections on the wound-healing phases and promising modifications of dressing materials for accelerated healing of infected wounds are discussed. The review paper mainly focuses on the novel findings on the use of antibiotics, nanoparticles, cationic organic agents, and plant-derived natural compounds (essential oils and their components, polyphenols, and curcumin) to develop antimicrobial wound dressings. The review article was prepared on the basis of scientific contributions retrieved from the PubMed database (supported with Google Scholar searching) over the last 5 years.

Reusable antimicrobial antibiotic-free dressings obtained by photopolymerization

In recent years significant efforts have been made to develop new materials for wound dressing with improved healing properties. However, the synthesis methods usually employed to this end are often complex or require several steps. We describe here the synthesis and characterization of antimicrobial reusable dermatological wound dressings based on N-isopropylacrylamide co-polymerized with [2-(Methacryloyloxy) ethyl] trimethylammonium chloride hydrogels (NIPAM-co-METAC). The dressings were obtained with a very efficient single-step synthesis procedure based on visible light (455 nm) by photopolymerization. To this end, F8BT nanoparticles of the conjugated polymer (poly(9,9-dioctylfluorene-alt-benzothiadiazole) - F8BT) were used as macro-photoinitiators, and a modified silsesquioxane was employed as crosslinker. Dressings obtained by this simple and gentle method show antimicrobial and wound healing properties, without the incorporation of antibiotics or any other additives.The physical and mechanical properties of these hydrogel-based dressings were evaluated, as well as their microbiological properties, through in vitro experiments. Results show that dressings with a molar ratio of METAC of 0.5 or higher exhibit high swelling capacity, appropriate water vapor transmission rate values, stability and thermal response, high ductility and adhesiveness. In addition, biological tests showed that the dressings have significant antimicrobial capacity. The best inactivation performance was found for hydrogels synthesized with the highest METAC content. The dressings were tested several times with fresh bacterial cultures, showing a bacterial kill efficiency of 99.99 % even after three repetitions in a row, employing the same dressing, demonstrating the intrinsic bactericidal property of the materials and their reusability. In addition, the gels show low hemolytic effect, high dermal biocompatibility and noticeable wound healing effects. Overall results demonstrate that some specific hydrogel formulations have potential application as dermatological dressings for wound healing and disinfection.

Hydrogel Complex Containing the Antimicrobial Peptide HX-12C Accelerates Healing of Infected Wounds.

Bacterial infections of the wound surface can be painful for patients, and traditional dressings do not effectively address this problem. In this study, an antimicrobial wound dressing is prepared using a novel antimicrobial peptide, HX-12C. This hydrogel system is based on the natural biomaterials sodium alginate and gelatin, utilizing calcium carbonate as a source of Ca2+ , and ionic cross-linking is facilitated by lowering the solution pH. The resulting sodium alginate/gelatin HX-12C-loaded hydrogel (CaAGEAM) has good mechanical and adhesion properties, biocompatibility and in vitro degradability. Its extraordinary antibacterial efficacy (>98%) is verified by an antibacterial experiment. More importantly, in vivo experiments further demonstrate its healing-promotion effect, with a 95% wound healing rate by day 9. Tissue staining demonstrates that the hydrogel containing antimicrobial peptides is effective in suppressing inflammation. The dressing promotes wound healing by stimulating the deposition of skin appendages and collagen. The results of this study suggest that composite hydrogels containing antimicrobial peptides are a promising new type of dressing to promote the healing of infected wounds.

Self-crosslinked polyvinyl alcohol/cellulose nanofibril cryogels loaded with synthesized aminophosphonates as antimicrobial wound dressings.

Microbial infection is the most common obstacle in the wound healing process, leading to wound healing impairment and complications and ultimately increasing morbidity and mortality. Due to the rising number of pathogens evolving resistance to the existing antibiotics used for wound care, alternative approaches are urgently required. In this study, α-aminophosphonate derivatives as antimicrobial agents were synthesized and incorporated into self-crosslinked tri-component cryogels composed of fully hydrolyzed polyvinyl alcohol (PVA-F), partially hydrolyzed polyvinyl alcohol (PVA-P), and cellulose nanofibrils (CNFs). Initially, the antimicrobial activity of four α-aminophosphonate derivatives against selected skin bacterial species was tested and their minimum inhibitory concentration was determined based on which the most effective compound was loaded into the cryogels. Next, the physical and mechanical properties of cryogels with various blending ratios of PVA-P/PVA-F and fixed amounts of CNFs were assessed, and drug release profiles and biological activities of drug-loaded cryogels were analyzed. Assessment of α-aminophosphonate derivatives showed the highest efficacy of a cinnamaldehyde-based derivative (Cinnam) against both Gram-negative and Gram-positive bacteria compared to other derivatives. The physical and mechanical properties of cryogels showed that PVA-P/PVA-F with a 50/50 blending ratio had the highest swelling ratio (1600%), surface area (523 m2 g-1), and compression recoverability (72%) compared to that with other blending ratios. Finally, antimicrobial and biofilm development studies showed that the cryogel loaded with a Cinnam amount of 2 mg (relative to polymer weight) showed the most sustained drug release profile over 75 h and had the highest efficacy against Gram-negative and Gram-positive bacteria. In conclusion, self-crosslinked tri-component cryogels loaded with the synthesized α-aminophosphonate derivative, having both antimicrobial and anti-biofilm formation properties, can have a significant impact on the management of uprising wound infection.

Cerium Nitrate Stiffens In Vitro Skin Models and Reduces Pseudomonas aeruginosa Pathogenicity and Penetration Through Skin Models.

Objective: Cerium nitrate (CeN) plus silver sulfadiazine (SSD) cream has been used for 40-plus years to manage burns. CeN produces a hardened eschar believed to resist bacterial colonization/infection. To evaluate this potential mechanism, we treated in vitro skin models or Pseudomonas aeruginosa with CeN and measured mechanical properties of the models and bacterial virulence, respectively. Approach: We treated three-dimensional-collagen matrix and ex-vivo-burned porcine skin with CeN and evaluated stiffness and P. aeruginosa penetration. In addition, we treated P. aeruginosa with CeN and evaluated the bacteria's motility, skin model penetration, susceptibility to be phagocytized by the human monocytic cell line THP-1, and ability to stimulate this cell line to produce cytokines. Results: CeN treatment of skin models stiffened them and made them resistant to P. aeruginosa penetration. Inversely, CeN treatment of P. aeruginosa reduced their motility, penetration through skin models (ex-vivo-burned porcine skin), and ability to stimulate cytokine production (tumor necrosis factor-α [TNF-α] and interleukin 8 [IL-8]) by THP-1 cells. In addition, CeN-treated Pseudomonas was more readily phagocytized by THP-1 cells. Finally, P. aeruginosa inoculated on CeN-treated ex-vivo-burned porcine skin was more susceptible to killing by a silver dressing. Innovation: In vitro skin models offer a platform for screening drugs that interfere with bacterial penetration into wounded tissue. Conclusion: CeN treatment reduced P. aeruginosa virulence, altered the mechanical properties of ex-vivo-burned porcine skin and collagen matrix, retarded penetration of P. aeruginosa through the skin models, and resulted in increased vulnerability of P. aeruginosa to killing by antimicrobial wound dressings. These data support the use of CeN in burn management.