Management Of Wound Infections Research Articles

Improving wound infection management: education and evaluation of an infection management pathway.

To assess the clinical impact and acceptance of an infection management (IM) pathway, designed to improve the consistency of care of wound infection when introduced, and supported by an educational programme. An education and evaluation programme (T3 programme) was-conducted in Portugal, Spain and Italy. This consisted of a two-hour educational, virtual seminar, followed by a four-week evaluation of an IM pathway during which survey data were collected on the impact of this pathway on clinician-selected patients. Finally, all participants reconvened for a virtual meeting during which the combined results were disseminated. The pathway provided guidance to clinicians regarding the targeted use of antimicrobial wound dressings according to the presence and absence of signs and symptoms of wound infection. Responses relating to 259 patients treated according to the IM pathway, 139 (53.7%) of whom had received previous antimicrobial treatment, were captured. Signs and symptoms of infection resolved within four weeks of treatment in >90% of patients. All 25 patients who had received prior antimicrobial treatment for ≥3 months experienced a resolution in the signs and symptoms of infection within four weeks. The majority of participating clinicians agreed that the IM pathway improved decision-making (94.9%) and confidence (97.3%), and helped to determine the correct antimicrobial treatment (91.4%) in the context of wound infection. The T3 programme was an efficient way to deliver a structured educational programme. The use of the IM pathway resulted in >90% of patients achieving resolution of their signs and symptoms of wound infection.

Antiadhesive, antibacterial, and anti-inflammatory sandwich-structured ZIF8-containing gauze for enhanced wound healing

Medical gauze is commonly used in clinical practice due to its low irritation, flexibility, and permeability. However, conventional gauze frequently lacks adequate antibacterial and anti-adhesion properties, and gauze that is only superhydrophobic or antibacterial seldom meets the full requirements of infected wound treatment. In this work, we report optimal air permeability, water and blood absorption, and biocompatibility, and effective antibacterial properties of a sandwich-structured gauze composed of a superhydrophobic outer layer, a zeolite imidazolate framework-8 (ZIF8) interlayer, and a superhydrophobic inner layer containing blood-drainage channels (denoted SZS gauze). Three ZIF8 interlayers, ZIF8-1, ZIF8-2, and ZIF8-3, were prepared by soaking medical gauze samples in a mixed solution of 50 mL methanol, 50 mL ethanol, and 0.25, 0.50, or 1.00 g zinc acetate before flat drying, and had Zn content of 0.28, 0.34, and 0.46at.%, respectively, and their corresponding SZS gauze samples are denoted SZS-1, SZS-2, and SZS-3, respectively. Among all gauze samples, the SZS-2 showed the highest cytocompatibility toward L929 cells and effective in vitro antibacterial ability against E.coli and S.aureus. In a rat subcutaneous inflammation model, the SZS-2 showed complete biosafety and the best antibacterial and anti-inflammatory effects against E.coli and S.aureus mixed bacteria among all gauze samples including standard medical gauze and a sandwich-structured gauze with a blank interlayer between two superhydrophobic layers. These findings indicate that the SZS-2 gauze is a promising candidate for advanced wound care, particularly in the management of infected wounds.

Evaluation of living bacterial therapy assisted by pH/reactive oxygen species dual-responsive sodium alginate-based hydrogel for wound infections

The enhancement of antimicrobial wound dressings is of utmost importance in light of the escalating risk of antibiotic resistance caused by excessive antibiotic usage. Conventional antimicrobial materials eradicate pathogenic bacteria while impeding the proliferation of beneficial bacteria during the management of wound infections, thereby disturbing the equilibrium of the skin micro-ecosystem and engendering recurrent cutaneous complications. Lactobacillus rhamnosus (L.rha) is a probiotic that can inhibit the growth of certain pathogenic bacteria by secreting a large number of metabolites. In this paper, we synthesized a cross-linker with a boric acid molecule (SPBA) from succinic acid and 4-(bromomethyl)phenylboronic acid, which formed a boric acid ester bond with a diol on the natural polysaccharide sodium alginate (SA), and obtained a pH/reactive oxygen species (ROS) dual-responsive hydrogel (SA-SPBA) for loading L.rha to treat wound infections. The SA-SPBA@L.rha hydrogel improves the survival of L.rha during storage and has good injectability as well as self-healing properties. The hydrogel showed good biocompatibility, the antimicrobial effect increases in a dose-dependent manner, and it has a certain antioxidant and anti-inflammatory capacity, accelerating wound repair. The use of SA-SPBA@L.rha hydrogel provides a safe and effective strategy for the repair of skin wound infections.

Preparation and characterization of a polyurethane-based sponge wound dressing with a superhydrophobic layer and an antimicrobial adherent hydrogel layer

Bacterial infection poses a significant impediment in wound healing, necessitating the development of dressings with intrinsic antimicrobial properties. In this study, a multilayered wound dressing (STPU@MTAI2/AM1) was reported, comprising a surface-superhydrophobic treated polyurethane (STPU) sponge scaffold coupled with an antimicrobial hydrogel. A superhydrophobic protective outer layer was established on the hydrophilic PU sponge through the application of fluorinated zinc oxide nanoparticles (F-ZnO NPs), thereby resistance to environmental contamination and bacterial invasion. The adhesive and antimicrobial inner layer was an attached hydrogel (MTAI2/AM1) synthesized through the copolymerization of N-[2-(methacryloyloxy)ethyl]-N, N, N-trimethylammonium iodide and acrylamide, exhibits potent adherence to dermal surfaces and broad-spectrum antimicrobial actions against resilient bacterial strains and biofilm formation. STPU@MTAI2/AM1 maintained breathability and flexibility, ensuring comfort and conformity to the wound site. Biocompatibility of the multilayered dressing was demonstrated through hemocompatibility and cytocompatibility studies. The multilayered wound dressing has demonstrated the ability to promote wound healing when addressing MRSA-infected wounds. The hydrogel layer demonstrates no secondary damage when peeled off compared to commercial polyurethane sponge dressing. The STPU@MTAI2/AM1-treated wounds were nearly completely healed by day 14, with an average wound area of 12.2 ± 4.3 %, significantly lower than other groups. Furthermore, the expression of CD31 was significantly higher in the STPU@MTAI2/AM1 group compared to other groups, promoting angiogenesis in the wound and thereby contributing to wound healing. Therefore, the prepared multilayered wound dressing presents a promising therapeutic candidate for the management of infected wounds. Statement of significanceHealing of chronic wounds requires avoidance of biofouling and bacterial infection. However developing a wound dressing which is both anti-biofouling and antimicrobial is a challenge. A multilayered wound dressing with multifunction was developed. Its outer layer was designed to be superhydrophobic and thus anti-biofouling, and its inner layer was broad-spectrum antimicrobial and could inhibit biofilm formation. The multilayered wound dressing with adhesive property could easily be removed from the wound surface preventing the cause of secondary damage. The multilayered wound dressing has demonstrated good abilities to promote MRSA-infected wound healing and presents a viable treatment for MRSA-infected wound.

Scalable and Versatile Metal Ion Solidificated Alginate Hydrogel for Skin Wound Infection Therapy.

Bacterial infections in wounds continue to be a major challenge in clinical settings worldwide and represent a significant threat to human health. This work proposes novel expandable and versatile methods for solidifying sodium alginate (SA) with metal ions (such as Fe3+ , Co2+ , Ni2+ , Cu2+ , and Zn2+ ) to create Metal-Alginate (M-Alg) hydrogel with adjustable morphology, composition, and microstructure. It conforms to the wound site, protects against second infection, reduces inflammation, and promotes the healing of infected wounds. Among these hydrogels, Cu-Alginate (Cu-Alg) shows excellent sterilization effect and good efficacy against both gram-positive and gram-negative bacteria, including multidrug-resistant (MDR) strains such as Methicillin-resistant Staphylococcus aureus (MRSA) and Carbapenem-resistant Klebsiella pneumoniae (CRKP) due to its dual antibacterial mechanisms: contact-killing and reactive oxygen species (ROS) burst. Importantly, it exhibits low cytotoxicity and biodegradability. This simple and cost-effective gel-based system has the potential to introduce an innovative approach to the management of wound infection and offers promising new perspectives for the advancement of wound care practice.

Mussel-inspired near-infrared light-responsive gelatin-based hydrogels for enhancing MRSA-infected wound healing

Infected wound management is a great challenge to healthcare, especially in emergencies such as accidents or battlefields. Hydrogels as wound dressings can replace or supplement traditional wound treatment strategies, such as bandages or sutures. It is significant to develop novel hydrogel-based wound dressings with simple operation, inexpensive, easy debridement, effective antibacterial, biocompatibility, etc. Here, we designed a novel gelatin-based hydrogel wound dressing Gel-TA-Fe3+. The hydrogels used tannic-modified gelatin as the main body and Fe3+ as the crosslinking agent to achieve a controllable rapid sol-gel transition. The hydrogels exhibited tough mechanical properties, excellent antibacterial ability, biocompatibility and an acceptable temperature response to near-infrared light (NIR). Moreover, the hydrogels could promote the healing process of MRSA-infected skin wound in rats. This multifunctional hydrogel was thought to have potential for emergency treatment of bacterial infected wound.

Integrated Bilayer Microneedle Dressing and Triboelectric Nanogenerator for Intelligent Management of Infected Wounds

AbstractThe integration of real‐time monitoring and on‐demand treatment has substantial potential to accelerate wound healing processes. In this context, versatile bilayer microneedles (MNs) and a triboelectric nanogenerator (TENG) are developed as a theranostic platform for efficient wound management. This platform provides benefits including controlling infection, promoting cell migration and proliferation, and the capability for biochemical sensing. The bilayer MNs comprise a solvable polyvinylpyrrolidone MN (pMN) affixed atop a conductive stainless‐steel MN (sMN). The robust sMN penetrates the requisite skin depth, while the pMN, infused with antibiotics, ensures sustained drug release upon dissolution in the interstitial fluids. Concurrently, the TENG generates electrical stimulation transmitted to the wound site through the conductive sMN, contributing to accelerated wound closure. Furthermore, the sMN, coated with silver and carbon nanotubes (CNT/Ag/sMN), functions as a transdermal electrochemical sensor to assess the wound state by detecting hydrogen peroxide and uric acid. Notably, in vivo animal studies have demonstrated that the MN‐TENG device not only effectively inhibits bacterial growth and expedites wound healing but also monitors wound biomarkers, thereby validating its utility in improving infected wound recovery. Consequently, this MN‐TENG based transdermal strategy fosters advancements in diagnostic and therapeutic technologies within wound management and related biomedical domains.

G‐Quadruplex/Hemin DNAzyme‐Functionalized Silver Nanoclusters with Synergistic Antibacterial and Wound Healing Capabilities for Infected Wound Management (Small 8/2024)

G‐Quadruplex/Hemin DNAzyme‐Functionalized Silver Nanoclusters with Synergistic Antibacterial and Wound Healing Capabilities for Infected Wound Management (Small 8/2024)

Gold nanoclusters encapsulated microneedle patches with antibacterial and self‐monitoring capacities for wound management

AbstractThe management of infected wounds is always of great significance and urgency in clinical and biomedical fields. Recent efforts in this area are focusing on the development of functional wound patches with effective antibacterial, drug delivery, and sensor properties. Here, we present novel hyaluronic acid (HA) microneedle patches with these features by encapsulating aminobenzeneboronic acid‐modified gold nanoclusters (A‐GNCs) for infected wound management. The A‐GNCs loaded microneedle patches were derived from negative‐mold replication and showed high mechanical strength to penetrate the skin. The release of the A‐GNCs was realized by the degradation of HA, and the self‐monitor of the released actives was based on the dynamic bright orange fluorescence emitted from A‐GNCs under ultraviolet radiation. As the A‐GNCs could destroy bacteria membranes, the microneedle patches were with excellent in vitro antibiosis ability. Based on these features, we have demonstrated the bacteria inhibition, residual drug self‐monitoring, and wound healing promotion abilities of the microneedle patches in Escherichia coli‐ or Staphylococcus aureus‐infected wound management. These results indicated the great potential of such A‐GNCs loaded microneedle patches for clinical applications.

Polymer-Based Functional Materials Loaded with Metal-Based Nanoparticles as Potential Scaffolds for the Management of Infected Wounds.

Wound infection due to bacterial invasion at the wound site is one of the primary challenges associated with delayed wound healing. Microorganisms tend to form biofilms that protect them from harm, leading to their multidrug resistance. The alarming increase in antibiotic resistance poses a threat to wound healing. Hence, the urgent need for novel wound dressing materials capable of managing bacterial infection is crucial for expediting wound recovery. There is considerable interest in polymeric wound dressings embedded with bioactive substances, such as metal-based nanoparticles, as potential solutions for treating microbially infected wounds. Metal-based nanoparticles have been widely used for the management of infected wounds due to their broad antimicrobial efficacy. This review focuses on polymer-based and bioactive wound dressings loaded with metal-based nanoparticles like silver, gold, magnesium oxide, or zinc oxide. When compared, zinc oxide-loaded dressings exhibited higher antibacterial activity against Gram-positive strains and silver nanoparticle-loaded dressings against gram-negative strains. However, wound dressings infused with both nanoparticles displayed a synergistic effect against both strains of bacteria. Furthermore, these dressings displayed antibiofilm activity and the generation of reactive oxygen species while accelerating wound closure both in vitro and in vivo.

Drug-free and multifunctional sodium bicarbonate/hyaluronic acid hybrid dressing for synergistic healing of infected wounds

Skin wounds are susceptible to microbial infections which commonly lead to the delayed wound healing. Rapid clearance of pathogens from the wound is of great significance and importance for efficient healing of the infected wounds. Herein, we report a multifunctional hybrid dressing, which simply combines sodium bicarbonate (NaHCO3) and hyaluronic acid (HA) for the synergistic wound healing. Addition of NaHCO3 allows the hybrid dressing to have the great antibacterial and antioxidant activity, while maintaining the intrinsic skin repair function of HA. As a result, NaHCO3/HA hybrid dressing showed the great antibacterial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) pathogens, the ability to improve the fibroblasts proliferation and migration, the cell-protection capacity under H2O2-induced oxidative stress, and most importantly, the great healing efficacy for the mice wound infected by S. aureus. We further found that the epidermal regeneration, the collagen deposition and the angiogenesis were enhanced by NaHCO3/HA hybrid dressing. All these effects were NaHCO3 concentration-dependent. Since the NaHCO3/HA hybrid dressing is drug-free, easily fabricated, biocompatible, and efficient for wound healing, it may have great potentials for clinical management of infected wounds.

Stingless bee honey: Nutritional, physicochemical, phytochemical and antibacterial validation properties against wound bacterial isolates.

With the rise of AMR the management of wound infections are becoming a big challenge. This has been attributed to the fact that most wound bacterial isolates have been found to possess various virulence factors like enzymes, toxins & biofilms production. Therefore, need for discovery of new lead compounds is paramount as such factors make these microbes to be resistant to already existing arsenal of antibiotics or even the immune system. This study aimed at documenting the nutritional, physicochemical, phytochemical and antibacterial properties of stingless bee honey. Isolation and characterization of bacterial isolates from 34 samples obtained from wounds of outpatients and surgical wards of Nakuru County Referral Hospital, Kenya was done. Various bacterial isolates (43) were isolated Staphylococcus aureus (34.8%) being predominant, followed by Pseudomonas aeruginosa (27.9%), Klebsiella pneumoniae (23.3%) and Escherichia coli (14.0%). A total of 36 out of the total isolates were genotypically characterized using molecular techniques detecting the prevalence of the following virulence genes; 16 srRNA (756 bp), hla (229 bp), cnf1 (426 bp), cnf2 (543 bp), hlyA (1011 bp), rmpA (461 bp), lasL (600 bp), gyrB (411 bp), khe (77 bp) and magA (128 bp). An assessment of the in vitro antibacterial activity of 26 stingless bee honey samples collected from their cerumen egg-shaped pots in Marigat sub-County, Baringo County, Kenya was done. Antibacterial properties of the stingless bee honey was done with varying susceptibility patterns being observed at different concentrations of honey impregnated discs (10x104, 20x104, 50x104 and 75x104 ml μg/ ml) giving mean inhibition diameters of 18.23 ± 0.4 mm (Staphylococcus aureus), 17.49 ± 0.3 mm (Pseudomonas aeruginosa), 16.05 ± 0.6 mm (Klebsiella pneumoniae) and 10.19 ± 0.5 mm (Escherichia coli) with a mean range of 14.54 ± 2.0 mm to 17.58 ± 3 mm. Higher susceptibility to honey was recorded across all the bacterial isolates compared to conventional antibiotics while the mean MIC and MBC of the honey were recorded at 62.5 ml μg/ ml and 250 ml μg/ ml respectively. Control bacterial isolates Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 27736 and Pseudomonas aeruginosa ATCC 27858 were used in the analysis. The stingless bee honey was found to be rich in various nutritive components like sugar (89.85 ± 5.07 g/100 g) and moisture (81.75 ± 10.35 mg/g) with a significant difference of P <0.05 as the main antibacterial components. Additionally, the stingless honey did possess water soluble vitamins, proteins and minerals of which potassium was the most dominant one. In regard to phytochemicals, on our preliminary analysis phenolic, flavonoid and carotenoid compounds were found to be present with phenolic compounds being the most dominant one. Stingless bee honey from Marigat, has antimicrobial properties which could be attributed to the rich phytochemicals it possesses and its physicochemical properties in addition to its high nutritive value.

Environmentally friendly polylysine gauze dressing for an innovative antimicrobial approach to infected wound management

Environmentally friendly polylysine gauze dressing for an innovative antimicrobial approach to infected wound management

Antimicrobial, Antioxidant, and Anti-Inflammatory Nanoplatform for Effective Management of Infected Wounds.

Burn wound healing continues to pose significant challenges due to excessive inflammation, the risk of infection, and impaired tissue regeneration. In this regard, an antibacterial, antioxidant, and anti-inflammatory nanocomposite (called HPA) that combines a nanosystem using hexachlorocyclotriphosphazene and the natural polyphenol of Phloretin with silver nanoparticles (AgNPs) is developed. HPA effectively disperses AgNPs to mitigate any toxicity caused by aggregation while also showingthe pharmacological activities of Phloretin. During the initial stage of wound healing, HPA rapidly releases silver ions from its surface to suppress bacterial activity. Moreover, these nanoparticles are pH-sensitive and degrade efficiently in the acidic infection microenvironment, gradually releasing Phloretin. This sustained release of Phloretin helps scavenge overexpressed reactive oxygen species in the infected microenvironment area, thus reducing the upregulation of pro-inflammatory cytokines. The antibacterial activity, free radical clearance, and regulation of inflammatory factors of HPA through in vitro experiments are validated. Additionally, its effects using an infectious burn mouse model in vivo are evaluated. HPA is found to promote collagen deposition and epithelialization in the wound area. With its synergistic antibacterial, antioxidant, and anti-inflammatory activities, as well as favorable biocompatibilities, HPA shows great promise as a safe and effective multifunctional nanoplatform for burn injury wound dressings.

Advancements in Surgical Wound infection Management

Surgical wound infections pose a substantial challenge in healthcare, affecting patient outcomes and healthcare costs. This comprehensive review explores recent advancements in the prevention and management of surgical wound infections. Innovations in infection prevention include antimicrobial dressings and closed-incision negative pressure wound therapy, which reduce the risk of infections. Minimally invasive surgery has gained popularity due to its potential to lower infection rates. Enhanced antimicrobial stewardship and personalized prophylactic antibiotics have emerged to minimize infection risk. Biofilm disruption and immunomodulation therapies aim to enhance infection resistance. Remote monitoring technologies facilitate early intervention. This review underscores the commitment to enhancing patient safety and healthcare efficiency in the context of surgical wound infections.

Biodegradable and pH-Responsive Amphiphilic Poly(succinimide) Derivatives for Triggered Release of Antibiotics for Management of Infected Wounds.

Wound infection has become a healthy economic burden globally. Current wound management mainly relies on the use of antibiotics; however, the misuse and overuse of antibiotics can easily result in antibiotic resistance. This study proposes a biodegradable, biocompatible, and pH-responsive amphiphilic 11-aminoundecanoic acid-grafted polysuccinimide (AUA-PSI) as a nanocarrier for drug encapsulation via nanoprecipitation. The succinimide groups in the backbone of PSI allow facile postfunctionalization via an aminolysis reaction. The degree of substitution of AUA can be modulated to adjust the degradation rate, pH sensitivity, and drug-release profile. Antibiotic rifampicin was incorporated with AUA-PSI to form Rif-AUA-PSI nanoparticles and demonstrated pH-responsiveness and antimicrobial activity. Because of the elevation of the pH value from pH = ∼ 5.5 in healthy skin to pH > 7 in an infected wound, Rif-AUA-PSI nanoparticles begin to decompose and release Rif upon the hydrolysis of succinimide/amide and deprotonation of carboxyl groups. The effective suppression of bacterial growth by Rif-AUA-PSI nanoparticles was demonstrated using a plate count method. More importantly, Rif-AUA-PSI nanoparticles were physically deposited on cotton gauze bandages as an antibiotic wound dressing. The Rif-AUA-PSI-modified gauze was applied to infected wounds on rats for wound management. The results show fast wound healing and inhibition of bacterial growth, which demonstrate that the method promotes modulable amphiphilicity, biodegradability, biocompatibility, pH-responsiveness, and facile modification for nanomedicine and medical devices.

Dissemination of blaNDM-5-carrying IncX3-type plasmid among non-clonal Escherichia coli strains colonising a dog with a skin infection caused by a carbapenem-resistant Klebsiella pneumoniae, United Kingdom

A successful outcome of a post-surgical wound infection management by a carbapenem-resistant Klebsiella pneumoniae is described in a dog. Four multidrug-resistant and carbapenem-resistant Escherichia coli strains belonging to ST410 (n = 1) and ST648 (n = 3) were isolated from faecal samples and nasal swabs of this dog at admission to a veterinary hospital in the United Kingdom, and one month after discharge. Whole-genome sequencing analysis suggests dissemination of a 46,161-bp IncX3 blaNDM-5-carrying plasmid among E. coli strains from the different lineages. In this study, the E. coli ST648 strains were virtually identical to each other (5 SNPs difference) indicating dissemination and persistence of this clone over time and across different anatomical sites in the same dog maybe due to the prolonged antimicrobial therapy. The carbapenemase carrying plasmid also showed homology with other publicly available plasmid sequences from Asian countries. These results suggests that plasmids may be a major vehicle in mediating the dissemination of carbapenem-resistance. Further studies investigating the selection and flow of plasmids carrying important resistance genes amongst companion animals are needed as it may further contaminate other environments posing a threat to public health.

Antibacterial-Antioxidative Thiolated Gelatin/Methacrylated Silk Fibroin Hydrogels with Nitric Oxide Release Catalyzed by Metal-Polyphenol Nanoparticles for MRSA-Infected Wound Healing.

Chronic wound infection often leads to irregular tissue closure and accompanies delayed healing and economy issues. Developing an ideal wound dressing that can control the occurrence of antibacterial infections and biological responses is highly desirable. In this study, a multifunctional hybrid hydrogel (GS@EG-Cu-CA NPs) containing synthesized thiolated gelatin, methacrylated silk fibroin, and (-)-epigallocatechin gallate-copper ionic-carrageenan nanoparticles (EG-Cu-CA NPs) was engineered by a thio-ene click reaction. The metal-polyphenol EG-Cu-CA NPs were encapsulated with kappa-carrageenan to enhance its aqueous-soluble, mechanical, and bioactive properties and endowed the hydrogel dressing with fascinating antibacterial, antioxidation, and nitric oxide (NO) generation by catalyzing. The hybrid hydrogels also illustrated a favorable cytocompatibility. Benefiting from the thio-ene click reaction, the hybrid hydrogels were injected and photocured rapidly in situ to cover an irregular wound. In an SD rat full-thickness skin-wound-infected model, the methicillin-resistant Staphylococcus aureus-infected wound covered with GS@EG-Cu-CA NPs was almost completely healed after 10 days. This study presents a facile design of hydrogel dressing incorporating metal-polyphenol nanoparticles, which demonstrates a promising potential way for dealing with effective wound infection management and other complicated wound healings.

G-Quadruplex/Hemin DNAzyme-Functionalized Silver Nanoclusters with Synergistic Antibacterial and Wound Healing Capabilities for Infected Wound Management.

Systematic management of infected wounds requires simultaneous antiinfection and wound healing, which has become the current treatment dilemma. Recently, a multifunctional silver nanoclusters (AgNCs)-based hydrogel dressing to meet these demands is developed. Here a diblock DNA with a cytosine-rich fragment (as AgNCs template) and a guanine-rich fragment (to form G-quadruplex/hemin DNAzyme, termed G4/hemin) is designed, for G4/hemin functionalization of AgNCs. Inside bacteria, G4/hemin can not only accelerate the oxidative release of Ag+ from AgNCs but also generate reactive oxygen species (ROS) via catalase- and peroxidase-mimic activities, which enhance the antibacterial effect. On the other hand, the AgNCs exhibit robust anti-inflammatory and antioxidative activities to switch M1 macrophages into M2 phenotype, which promotes wound healing. Moreover, the hemin is released to upregulate the heme oxygenase-1, an intracellular enzyme that can relieve oxidative stress, which significantly alleviates the cytotoxicity of silver. As a result, such silver-based dressing achieves potent therapeutic efficacy on infected wounds with excellent biosafety.

Bactericidal effect of Iberin combined with photodynamic antimicrobial chemotherapy against Pseudomonas aeruginosa biofilm cultured on ex vivo wound model

Wounds infected by Pseudomonas aeruginosa (P. aeruginosa) biofilms are characterized by poor healing and by being long lasting. Pyocyanin and pyoverdine are exotoxins that contribute to P. aeruginosa pathogenicity in wound infections and are known as virulence factors. Despite the usefulness of antimicrobial photodynamic therapy (PDT) in the management of wound infections, biofilms are hurdle for microbial photoinactivation. Quorum sensing (QS) is a cell density-dependent chemical signaling system P. aeruginosa uses to regulate biofilm formation and virulence factors production. In the current study, QS attenuation was used in combination with PDT against P. aeruginosa biofilm cultured on skin explant. Iberin is a QS inhibitor that attenuates P. aeruginosa virulence and affects biofilm integrity. The antibiofilm and QS inhibitory activities of iberin in combination with either riboflavin or 5,10,15,20-Tetrakis(1-methyl-4-pyridinio) porphyrin tetra p-toluenesulfonate (TMP) mediated PDT were investigated using viable count method and pyocyanin and pyoverdine assays, respectively.No bactericidal activity was reported when iberin was added to a mature biofilm (24 h) followed by PDT. When added to a growing biofilm at multiple time points (0 h, 24 h and 48 h), iberin inhibited P. aeruginosa biofilm QS signaling system. This inhibitory effect resulted in an observable decrease in the levels of the QS-regulated virulence factors, pyocyanin and pyoverdine, without any effect on the growth of the biofilm cultures. These changes in biofilm virulence were associated with a decrease in biofilm resistance to PDT and caused bactericidal effect upon photosensitizers treatment and irradiation. Iberin-treated-riboflavin-mediated PDT resulted in a significant 1.3 log reduction in biofilm population. Similarly, iberin-treated-TMP-mediated PDT caused a significant 1.8 log reduction in biofilm population. The combination of QS inhibitor with PDT is a promising alternative antimicrobial therapy for the management of biofilms.