Tooth-Whitening with a Novel Phthalimido Peroxy Caproic Acid: Short Communication.

Professional tooth whitening in the dental office is a popular cosmetic procedure and is performed under carefully monitored conditions. This allows the controlled application of a relatively high concentration of bleaching ingredients based on hydrogen peroxide or peroxide derivatives which produce reactive oxygen species, and consequently induce enamel erosion, alteration of the microhardness of the teeth, irritation of the gums, pain or post bleach sensitivity. This short communication describes the successful and reliable application of a new professional tooth whitening technique using a novel phthalimido peroxycaproic acid complex while avoiding reactive oxygen species.

A rapid and specific antimicrobial resistance detection of Escherichia coli via magnetic nanoclusters.

Drinking water contamination, often caused by bacteria, leads to substantial numbers of diarrhea deaths each year, especially in developing regions. Human urine as a source of fertilizer, when handled improperly, can contaminate drinking water. One dominant bacterial pathogen in urine is Escherichia coli, which can trigger serious waterborne/foodborne diseases. Considering the prevalence of the multi-drug resistant extended-spectrum beta-lactamase (ESBL) producing E. coli, a rapid detection method for resistance is highly desired. In this work, we developed a method for quick identification of E. coli and, at the same time, capable of removal of general bacterial pathogens from human urine. A specific peptide GRHIFWRRGGGHKVAPR, reported to have a strong affinity to E. coli, was utilized to modify the PEGylated magnetic nanoclusters, resulting in a specific capture and enrichment of E. coli from the bacteria-spiked artificial urine. Subsequently, a novel luminescent probe was applied to rapidly identify the antimicrobial resistance of the collected E. coli within 30 min. These functionalized magnetic nanoclusters demonstrate a promising prospect to rapidly detect ESBL E. coli in urine and contribute to reducing drinking water contamination.

Quaternary ammonium-based coating of textiles is effective against bacteria and viruses with a low risk to human health.

While the global healthcare system is slowly recovering from the COVID-19 pandemic, new multi-drug-resistant pathogens are emerging as the next threat. To tackle these challenges there is a need for safe and sustainable antiviral and antibacterial functionalized materials. Here we develop an 'easy-to-apply' procedure for the surface functionalization of textiles, rendering them antiviral and antibacterial and assessing the performance of these textiles. A metal-free quaternary ammonium-based coating was applied homogeneously and non-covalently to hospital curtains. Abrasion, durability testing, and aging resulted in little change in the performance of the treated textile. Additionally, qualitative and quantitative antibacterial assays on Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumanii revealed excellent antibacterial activity with a CFU reduction of 98-100% within only 4 h of exposure. The treated curtain was aged 6 months before testing. Similarly, the antiviral activity tested according to ISO-18184 with murine hepatitis virus (MHV) showed > 99% viral reduction with the functionalized curtain. Also, the released active compounds of the coating 24 ± 5 µg mL-1 revealed no acute in vitro skin toxicity (IC50: 95 µg mL-1) and skin sensitization. This study emphasizes the potential of safe and sustainable metal-free textile coatings for the rapid antiviral and antibacterial functionalization of textiles.

Topical application of Lactobacilli successfully eradicates Pseudomonas aeruginosa biofilms and promotes wound healing in chronic wounds.

Chronic wounds are difficult to treat due to the presence of biofilm which prevents wound healing. Pseudomonas aeruginosa is one of the most common pathogens found in chronic wounds and conventional treatment strategies have been ineffective in the eradication of its biofilm, without harming the surrounding healthy tissue at the same time. Here, we introduced an innovative approach applying the probiotic product Bio-K+ (containing three lactobacilli) topically as an antimicrobial and antibiofilm agent. We identified lactic acid as the main active component. While antibiotics and antiseptics such as silver-ions only demonstrated limited efficacy, Bio-K+ was able to completely eradicate mature P. aeruginosa biofilms established in an in-vitro and ex-vivo human skin model. Furthermore, it demonstrated biocompatibility in the co-culture with human dermal fibroblasts and accelerated the migration of fibroblasts in a cell migration assay promoting wound healing. To enhance clinical practicability, we introduced Bio-K+ into the hydrocolloid dressing Aquacel, achieving sustained release of lactic acid and biofilm eradication. This new treatment approach applying probiotics could represent a major improvement in the management of chronic wounds and can be extended in treating other biofilm-associated infections.

Functional Fiber Membranes with Antibacterial Properties for Face Masks.

Reusable face masks are an important alternative for minimizing costs of disposable and surgical face masks during pandemics. Often complementary to washing, a prolonged lifetime of face masks relies on the incorporation of self-cleaning materials. The development of self-cleaning face mask materials requires the presence of a durable catalyst to deactivate contaminants and microbes after long-term use without reducing filtration efficiency. Herein, we generate self-cleaning fibers by functionalizing silicone-based (polydimethylsiloxane, PDMS) fibrous membranes with a photocatalyst. Coaxial electrospinning is performed to fabricate fibers with a non-crosslinked silicone core within a supporting shell scaffold, followed by thermal crosslinking and removal of the water-soluble shell. Photocatalytic zinc oxide nanoparticles (ZnO NPs) are immobilized on the PDMS fibers by colloid-electrospinning or post-functionalization procedures. The fibers functionalized with ZnO NPs can degrade a photo-sensitive dye and display antibacterial properties against Gram-positive and Gram-negative bacteria (Escherichia coli and Staphylococcus aureus) due to the generation of reactive oxygen species upon irradiation with UV light. Furthermore, a single layer of functionalized fibrous membrane shows an air permeability in the range of 80-180 L/m2s and 65% filtration efficiency against fine particulate matter with a diameter less than 1.0 µm (PM1.0). Supplementary Information: The online version contains supplementary material available at 10.1007/s42765-023-00291-7.

Identification of Potential Antimicrobial Targets of Pseudomonas aeruginosa Biofilms through a Novel Screening Approach.

Pseudomonas aeruginosa is an opportunistic pathogen of considerable medical importance, owing to its pronounced antibiotic tolerance and association with cystic fibrosis and other life-threatening diseases. The aim of this study was to highlight the genes responsible for P. aeruginosa biofilm tolerance to antibiotics and thereby identify potential new targets for the development of drugs against biofilm-related infections. By developing a novel screening approach and utilizing a public P. aeruginosa transposon insertion library, several biofilm-relevant genes were identified. The Pf phage gene (PA0720) and flagellin gene (fliC) conferred biofilm-specific tolerance to gentamicin. Compared with the reference biofilms, the biofilms formed by PA0720 and fliC mutants were completely eliminated with a 4-fold-lower gentamicin concentration. Furthermore, the mreC, pprB, coxC, and PA3785 genes were demonstrated to play major roles in enhancing biofilm tolerance to gentamicin. The analysis of biofilm-relevant genes performed in this study provides important novel insights into the understanding of P. aeruginosa antibiotic tolerance, which will facilitate the detection of antibiotic resistance and the development of antibiofilm strategies against P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen of high medical importance and is one of the main pathogens responsible for the mortality of patients with cystic fibrosis. In addition to inherited antibiotic resistance, P. aeruginosa can form biofilms, defined as communities of microorganisms embedded in a self-produced matrix of extracellular polymeric substances adhering to each other and/or to a surface. Biofilms protect bacteria from antibiotic treatments and represent a major reason for antibiotic failure in the treatment of chronic infections caused by cystic fibrosis. Therefore, it is crucial to develop new therapeutic strategies aimed at specifically eradicating biofilms. The aim of this study was to generalize a novel screening method for biofilm research and to identify the possible genes involved in P. aeruginosa biofilm tolerance to antibiotics, both of which could improve the understanding of biofilm-related infections and allow for the identification of relevant therapeutic targets for drug development.

Specific capture of Pseudomonas aeruginosa for rapid detection of antimicrobial resistance in urinary tract infections.

Urinary tract infections (UTIs) are among the most predominant microbial diseases, leading to substantial healthcare burdens and threatening human well-being. UTIs can become more critical when caused by Pseudomonas aeruginosa, particularly by antimicrobial-resistant types. Thereby a rapid diagnosis and identification of the antimicrobial-resistant P. aeruginosa can support and guide an efficient medication and an effective treatment toward UTIs. Herein, we designed a platform for prompt purification, and effective identification of P. aeruginosa to combat the notorious P. aeruginosa associated UTIs. A peptide (QRKLAAKLT), specifically binding to P. aeruginosa, was grafted onto PEGylated magnetic nanoclusters and enabled a successful capture and enrichment of P. aeruginosa from artificial human urine. Rapid identification of antimicrobial resistance of the enriched P. aeruginosa can be moreover accomplished within 30 min. These functionalized magnetic nanoclusters demonstrate a prominent diagnostic potential to combat P. aeruginosa associated UTIs, which can be extended to other P. aeruginosa involved infections.

Ultrafast Determination of Antimicrobial Resistant Staphylococcus aureus Specifically Captured by Functionalized Magnetic Nanoclusters.

Sepsis, the systemic response to infection, is a life-threatening situation for patients and leads to high mortality, especially when caused by antimicrobial resistant pathogens. Prompt diagnosis and identification of the pathogenic bacteria, including their antibiotic resistance, are highly desired to yield a timely decision for treatment. Here, we aim to develop a platform for rapid isolation and efficient identification of Staphylococcus aureus, the most frequently occurring pathogen in sepsis. A peptide (VPHNPGLISLQG, SA5-1), specifically binding to S. aureus, was conjugated to the PEGylated magnetic nanoclusters, successfully enabling the specific capture and enrichment of S. aureus from blood serum. Consequently, fast detection of the antimicrobial resistance of the collected S. aureus was achieved within 30 min using a novel luminescent probe. These magnetic nanoclusters manifest a promising diagnostic prospect to combat sepsis.

Advanced antifouling and antibacterial hydrogels enabled by controlled thermo-responses of a biocompatible polymer composite.

To optimally apply antibiotics and antimicrobials, smart wound dressing conferring controlled drug release and preventing adhesions of biological objects is advantageous. Poly(N-isopropylacrylamide) (PNIPAAm), a conventional thermo-responsive polymer, and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), a typical antifouling polymer, have therefore potential to be fabricated as copolymers to achieve dual functions of thermo-responsiveness and antifouling. Herein, a hydrogel made of PNIPAM-co-PMPC was designed and loaded with octenidine, a widely applied antimicrobial agent for wound treatment, to achieve both antifouling and triggered drug release. The thermo-switch of the fabricated hydrogel allowed 25-fold more octenidine release at 37 °C (infected wound temperature) than at 30 °C (normal skin temperature) after 120 minutes, which led to at least a 3 lg reduction of the viable bacteria at 37 °C on artificially infected wounds. Furthermore, we pioneeringly assessed the antifouling property of the material in PBS buffer using single molecule/cell/bacterial force spectroscopy, and revealed that the fabricated hydrogel displayed distinctive antifouling properties against proteins, mammalian cells, and bacteria. This work demonstrated a promising design of a hydrogel applicable for preventing and treating wound infections. The concept of dual-functional materials can be envisaged for other clinical applications related to the prevention of biofilm-associated infections, such as urinary catheters, stents, and dental implants.

Uncoupling bacterial attachment on and detachment from polydimethylsiloxane surfaces through empirical and simulation studies.

Bacterial infections related to medical devices can cause severe problems, whose solution requires in-depth understanding of the interactions between bacteria and surfaces. This work investigates the influence of surface physicochemistry on bacterial attachment and detachment under flow through both empirical and simulation studies. We employed polydimethylsiloxane (PDMS) substrates having different degrees of crosslinking as the model material and the extended Derjaguin - Landau - Verwey - Overbeek model as the simulation method. Experimentally, the different PDMS materials led to similar numbers of attached bacteria, which can be rationalized by the identical energy barriers simulated between bacteria and the different materials. However, different numbers of residual bacteria after detachment were observed, which was suggested by simulation that the detachment process is determined by the interfacial physicochemistry rather than the mechanical property of a material. This finding is further supported by analyzing the bacteria detachment from PDMS substrates from which non-crosslinked polymer chains had been removed: similar numbers of residual bacteria were found on the extracted PDMS substrates. The knowledge gained in this work can facilitate the projection of bacterial colonization on a given surface.

pH-responsive silica nanoparticles for the treatment of skin wound infections.

Chronic wounds are not only a burden for patients but also challenging for clinic treatment due to biofilm formation. Here, we utilized the phenomenon that chronic wounds possess an elevated local pH of 8.9 and developed pH-sensitive silica nanoparticles (SiNPs) to achieve a targeted drug release on alkaline wounds and optimized drug utility. Chlorhexidine (CHX), a disinfectant and antiseptic, was loaded into SiNPs as the model drug. The loaded CHX displayed a release 4 - 5 fold higher at pH 8.0 and 8.5 than at pH 6.5, 7.0 and 7.4. CHX-SiNPs furthermore exhibited a distinctive antibacterial activity at pH 8.0 and 8.5 against both Gram-negative and -positive bacterial pathogens, while no cytotoxicity was found according to cell viability analysis. The CHX-SiNPs were further formulated into alginate hydrogels to allow ease of use. The antibacterial efficacy of CHX-SiNPs was then studied with artificial wounds on ex vivo human skin. Treatment with CHX-SiNPs enabled nearly a 4-lg reduction of the viable bacterial cells, and the alginate formulated CHX-SiNPs led to almost a 3-lg reduction compared to the negative controls. The obtained results demonstrated that CHX-SiNPs are capable of efficient pH-triggered drug release, leading to high antibacterial efficacy. Moreover, CHX-SiNPs enlighten clinic potential towards the treatment of chronic wound infections. STATEMENT OF SIGNIFICANCE: A platform for controlled drug release at a relatively high pH value i.e., over 8, was established by tuning the physical structures of silica nanoparticles (SiNPs). Incorporation of chlorhexidine, an antimicrobial agent, into the fabricated SiNPs allowed a distinctive inhibition of bacterial growth at alkaline pHs, but not at acidic pHs. The efficacy of the SiNPs loaded with chlorhexidine in treating wound infections was further validated by utilizing ex vivo human skin samples. The presented work demonstrates clinic potential of employing alkaline pH as a non-invasive stimulus to achieve on-demand delivery of antimicrobials through SiNPs, showcasing a valuable approach to treating bacterial infections on chronic wounds.

Photo-activated titanium surface confers time dependent bactericidal activity towards Gram positive and negative bacteria.

Titanium (Ti)-based implants are broadly applied in the medical field, but their related infections can lead to implant failure. Photo-irradiation of metal materials to generate antimicrobial agents, an alternative to antibiotics, is a promising method to reduce bacterial infection and antibiotic usage. It is therefore important to understand how bacterial pathogens respond to Ti surfaces. Here, Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus, the most prevalent pathogens linked to healthcare-associated infections, were used as model strains. Two different kinds of Ti surfaces respectively stored in dry condition and 0.9 % NaCl solution were applied. Upon UV irradiation and in the absence of bacteria, both tested surfaces exhibited similar bactericidal activity, even though the surfaces stored in 0.9 % NaCl solution generated a slightly higher level of reactive oxygen species (ROS). Interestingly, P. aeruginosa and S. aureus responded to the irradiated Ti surfaces differently regarding interaction time: the number of viable P. aeruginosa was reduced up to 90 % after 30 min interaction with the treated surfaces compared to the untreated ones, but this reduction is lessened to 69 %-81 % after 240 min. By contrast, UV treatment of surfaces did not impact the viability of S. aureus after 30 min interaction, however, led to more than 99 % reduction after 240 min incubation. These results provide first experimental evidence that Gram negative and positive bacterial species respond to ROS with different inactivation kinetics. This work also demonstrated that treatment with photo-irradiation in the absence of bacteria conferred Ti surfaces with efficient bactericidal activity.

Bioresponsive Hybrid Nanofibers Enable Controlled Drug Delivery through Glass Transition Switching at Physiological Temperature.

To avoid excessive usage of antibiotics and antimicrobial agents, smart wound dressings permitting controlled drug release for treatment of bacterial infections are highly desired. In search of a sensitive stimulus to activate drug release under physiological conditions, we found that the glass transition temperature (Tg) of a polymer or polymer blend can be an ideal parameter because a thermal stimulus can regulate drug release at the physiological temperature of 37 °C. A well-tuned Tg for a controlled drug release from fibers at 37 °C was achieved by varying the blending ratio of Eudragit® RS 100 and poly(methyl methacrylate). Octenidine, an antimicrobial agent often used in wound treatment, was encapsulated into the polymer blend during the electrospinning process and evaluated for its controlled release based on modulation of temperature. The thermal switch of the nanofibrous membranes can be turned "on" at physiological temperature (37 °C) and "off" at room temperature (25 °C), conferring a controlled release of octenidine. It was found that octenidine can be released in an amount at least 8.5 times higher (25 mg·L-1) during the "on" stage compared to the "off" stage after 24 h, which was regulated by the wet Tg (34.8-36.5 °C). The "on"/"off" switch for controlled drug release can moreover be repeated at least 5 times. Furthermore, the fabricated nanofibrous membranes displayed a distinctive antibacterial activity, causing a log3 reduction of the viable cells for both Gram negative and positive pathogens at 37 °C, when the thermal switch was "on". This study forms the groundwork for a treatment concept where no external stimulus is needed for the release of antimicrobials at physiological conditions, and will help reduce the overuse of antibiotics by allowing controlled drug release.

Symptoms Associated With Long-term Double-J Ureteral Stenting and Influence of Biofilms.

OBJECTIVE: To assess the symptoms associated with long-term Double-J ureteral stenting including the influence of biofilms on ureteral stents. METHODS: Patients with long-term (>8 weeks) uni- or bilateral ureteral stents completed the Ureteral Stent Symptoms Questionnaire (USSQ) at the day of stent exchange. Repeated assessment of patients was possible to allow for analysis of intraindividual changes. Assessment of biofilm mass on the stents was performed according to a validated method, its correlation with the USSQ total score was defined as primary outcome. Secondary outcomes included further analyses of stent-associated symptoms and their temporal course. RESULTS: A total of 87 stent indwelling periods in 35 patients were investigated. Median USSQ total score did not differ significantly between unilateral and bilateral stenting (42 vs 39 points; P = .17). An increasing total stent treatment time up to study inclusion did not correlate with the USSQ total score, but was significantly correlated with less urinary symptoms and a better quality of life. USSQ total score and subscores within individual patients did not significantly increase or decrease over the sequence of stent indwelling periods. Higher total biofilm masses were not associated with higher USSQ total scores or subscores. CONCLUSION: Long-term Double-J stenting provides a valuable treatment option, if stent-associated symptoms are low during the initial indwelling period. Thus, symptoms remain stable over the long-term course and the majority of patients are satisfied with the treatment. Furthermore, biofilm formation on ureteral stents does not seem to be the relevant driver of symptoms.

Role of the Surface Nanoscale Roughness of Stainless Steel on Bacterial Adhesion and Microcolony Formation.

Hospital-acquired infections can cause serious complications and are a severe problem because of the increased emergence of antibiotic-resistant bacteria. Biophysical modification of the material surfaces to prevent or reduce bacteria adhesion is an attractive alternative to antibiotic treatment. Since stainless steel is a widely used material for implants and in hospital settings, in this work, we used stainless steel to investigate the effect of the material surface topographies on bacterial adhesion and early biofilm formation. Stainless steel samples with different surface roughnesses Rq in a range of 217.9-56.6 nm (Ra in a range of 172.5-45.2 nm) were fabricated via electropolishing and compared for adhesion of bacterial pathogens Pseudomonas aeruginosa and Staphylococcus aureus. It was found that the number of viable cells on the untreated rough surface was at least 10-fold lower than those on the electropolished surfaces after 4 h of incubation time for P. aeruginosa and 15-fold lower for S. aureus. Fluorescence images and scanning electron microscopy images revealed that the bacterial cells tend to adhere individually as single cells on untreated rough surfaces. In contrast, clusters of the bacterial cells (microcolonies) were observed on electropolished smooth surfaces. Our study demonstrates that nanoscale surface roughness can play an important role in restraining bacterial adhesion and formation of microcolonies.

Extraction of Biofilms From Ureteral Stents for Quantification and Cultivation-Dependent and -Independent Analyses.

Ureteral stenting is a common surgical procedure, which is associated with a high morbidity and economic burden, but the knowledge on the link between biofilms on these stents, morbidity, and the impact of the involved microbiota is still limited. This is partially due to a lack of methods that allow for a controlled extraction of the biofilms from stents. Development of an appropriate in vitro model to assess prevention of biofilm formation by antimicrobial coatings and biomaterials requires a profound understanding of the biofilm composition, including the involved microbiota. This work describes an analytical pipeline for the extraction of native biofilms from ureteral stents for both cultivation-dependent and -independent analysis, involving a novel mechanical abrasion method of passing stent samples through a tapered pinhole. The efficiency of this novel method was evaluated by quantifying the removed biofilm mass, numbers of cultivable bacteria, calcium content, and microscopic stent analysis after biofilm removal using 30 clinical stent samples. Furthermore, the extraction of in vitro formed Escherichia coli biofilms was evaluated by universal 16S quantitative PCR, a cultivation-independent method to demonstrate efficient biofilm removal by the new approach. The novel method enables effective contamination-free extraction of the biofilms formed on ureteral stents and their subsequent quantification, and it represents a useful tool for comprehensive examinations of biofilms on ureteral stents.