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 (SPBA) with a boric acid molecule 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.

Alginate based biomaterials for hemostatic applications: Innovations and developments.

Development of the efficient hemostatic materials is an essential requirement for the management of hemorrhage caused by the emergency situations to avert most of the casualties. Such injuries require the use of external hemostats to facilitate the immediate blood clotting. A variety of commercially available hemostats are present in the market but most of them are associated with limitations such as exothermic reactions, low biocompatibility, and painful removal. Thus, fabrication of an ideal hemostatic composition for rapid blood clot formation, biocompatibility, and antimicrobial nature presents a real challenge to the bioengineers. Benefiting from their tunable fabrication properties, alginate-based hemostats are gaining importance due to their excellent biocompatibility, with >85 % cell viability, high absorption capacity exceeding 500 %, and cost-effectiveness. Furthermore, studies have estimated that wounds treated with sodium alginate exhibited a blood loss of 0.40 ± 0.05 mL, compared to the control group with 1.15 ± 0.13 mL, indicating its inherent hemostatic activity. This serves as a solid foundation for designing future hemostatic materials. Nevertheless, various combinations have been explored to further enhance the hemostatic potential of sodium alginate. In this review, we have discussed the possible role of alginate based composite hemostats incorporated with different hemostatic agents, such as inorganic materials, polymers, biological agents, herbal agents, and synthetic drugs. This article outlines the challenges which need to be addressed before the clinical trials and give an overview of the future research directions.

Bioactive metabolites of Streptomyces misakiensis display broad-spectrum antimicrobial activity against multidrug-resistant bacteria and fungi.

Background: Antimicrobial resistance is a serious threat to public health globally. It is a slower-moving pandemic than COVID-19, so we are fast running out of treatment options. Purpose: Thus, this study was designed to search for an alternative biomaterial with broad-spectrum activity for the treatment of multidrug-resistant (MDR) bacterial and fungal pathogen-related infections. Methods: We isolated Streptomyces species from soil samples and identified the most active strains with antimicrobial activity. The culture filtrates of active species were purified, and the bioactive metabolite extracts were identified by thin-layer chromatography (TLC), preparative high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentrations (MICs) of the bioactive metabolites against MDR bacteria and fungi were determined using the broth microdilution method. Results: Preliminary screening revealed that Streptomyces misakiensis and S. coeruleorubidus exhibited antimicrobial potential. The MIC50 and MIC90 of S. misakiensis antibacterial bioactive metabolite (ursolic acid methyl ester) and antifungal metabolite (tetradecamethylcycloheptasiloxane) against all tested bacteria and fungi were 0.5 µg/ml and 1 µg/mL, respectively, versus S. coeruleorubidus metabolites: thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC50: 2 µg/ml and MIC90: 4 µg/mL) and fungi (MIC50: 4 µg/ml and MIC90: 8 µg/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of Streptococcus pyogenes, S. agalactiae, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovars, colistin-resistant Aeromonas hydrophila and K. pneumoniae, and vancomycin-resistant Staphylococcus aureus. Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant Candida albicans, Cryptococcus neoformans, C. gattii, Aspergillus flavus, A. niger, and A. fumigatus. Ursolic acid methyl ester was applied in vivo for treating S. aureus septicemia and K. pneumoniae pneumonia models in mice. In the septicemia model, the ursolic acid methyl ester-treated group had a significant 4.00 and 3.98 log CFU/g decrease (P < 0.05) in liver and spleen tissue compared to the infected, untreated control group. Lung tissue in the pneumonia model showed a 2.20 log CFU/g significant decrease in the ursolic acid methyl ester-treated group in comparison to the control group. The haematological and biochemical markers in the ursolic acid methyl ester-treated group did not change in a statistically significant way. Moreover, no abnormalities were found in the histopathology of the liver, kidneys, lungs, and spleen of ursolic acid methyl ester-treated mice in comparison with the control group. Conclusion: S. misakiensis metabolite extracts are broad-spectrum antimicrobial biomaterials that can be further investigated for the potential against MDR pathogen infections. Hence, it opens up new horizons for exploring alternative drugs for current and reemerging diseases.

Selenium Silk Nanostructured Films with Antifungal and Antibacterial Activity.

The rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. Therefore, one orthogonal approach is to explore biomaterials with physical modes of action that have the potential to generate antimicrobial activity and, in some cases, even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and noncytotoxic toward mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a 2-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next-generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials.

Dental Materials for Oral Microbiota Dysbiosis: An Update.

The balance or dysbiosis of the microbial community is a major factor in maintaining human health or causing disease. The unique microenvironment of the oral cavity provides optimal conditions for colonization and proliferation of microbiota, regulated through complex biological signaling systems and interactions with the host. Once the oral microbiota is out of balance, microorganisms produce virulence factors and metabolites, which will cause dental caries, periodontal disease, etc. Microbial metabolism and host immune response change the local microenvironment in turn and further promote the excessive proliferation of dominant microbes in dysbiosis. As the product of interdisciplinary development of materials science, stomatology, and biomedical engineering, oral biomaterials are playing an increasingly important role in regulating the balance of the oral microbiome and treating oral diseases. In this perspective, we discuss the mechanisms underlying the pathogenesis of oral microbiota dysbiosis and introduce emerging materials focusing on oral microbiota dysbiosis in recent years, including inorganic materials, organic materials, and some biomolecules. In addition, the limitations of the current study and possible research trends are also summarized. It is hoped that this review can provide reference and enlightenment for subsequent research on effective treatment strategies for diseases related to oral microbiota dysbiosis.

Bacteriophage-Loaded Poly(lactic-co-glycolic acid) Microparticles Mitigate Staphylococcus aureus Infection and Cocultures of Staphylococcus aureus and Pseudomonas aeruginosa.

Lung infections caused by Gram-positive Staphylococcus aureus (S. aureus) and coinfections caused by S. aureus and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) are challenging to treat, especially with the rise in the number of antibiotic-resistant strains of these pathogens. Bacteriophage (phage) are bacteria-specific viruses that can infect and lyse bacteria, providing a potentially effective therapy for bacterial infections. However, the development of bacteriophage therapy is impeded by limited suitable biomaterials that can facilitate effective delivery of phage to the lung. Here, the ability of porous microparticles engineered from poly(lactic-co-glycolic acid) (PLGA), a biodegradable polyester, to effectively deliver phage to the lung, is demonstrated. The phage-loaded microparticles (phage-MPs) display potent antimicrobial efficacy against various strains of S. aureus in vitro and in vivo, and arrest the growth of a clinical isolate of S. aureus in the presence of sputum supernatant obtained from cystic fibrosis patients. Moreover, phage-MPs efficiently mitigate in vitro cocultures of S. aureus and P. aeruginosa and display excellent cytocompatibility with human lung epithelial cells. Therefore, phage-MPs represents a promising therapy to treat bacterial lung infection.

Antimicrobial properties of dental cements modified with zein-coated magnesium oxide nanoparticles.

The aim of this study was to test the antimicrobial properties of dental cements modified with magnesium oxide (MgO) nanoparticles. Zein-modified MgO nanoparticles (zMgO) in concentrations (0.0, 0.3, 0.5, and 1.0%) were mixed with dental cements (Fuji II, Rely X Temp E, Ionoglass Cem, Es Temp NE, and System P link). Eight discs were fabricated from each zMgO-cement pair for a total of 32 specimens for each cement. Characterization of the dental cements incorporating zMgO was done by X-ray Diffraction (XRD) and Field Emission Scanning Electron Microscopy (FESEM). The antimicrobial properties of the mixtures were tested using direct contact and agar diffusion assays against Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Candida albicans. Data was analyzed using two-way analysis of variance and LSD post hoc test at 0.05 significance level. XRD spectra showed sharp peaks of zMgO indicating its high crystalline nature, while the amorphous dental cements with zMgO had broad peaks. FESEM analysis showed a uniform distribution of the zMgO nanoparticles in the cement. There were significant inhibition zone values associated with all concentrations of zMgO-cement mixtures tested compared to controls (p < 0.001) with a dose-response recorded only with Fuji II. Optical density values were significantly lower in zMgO groups compared to controls for all microorganisms. The effect was most prominent with Rely X against C. albicans and S. aureus. Dental cements containing zMgO showed significant antimicrobial properties that were dependent on the specific initial cement substrate.

Antimicrobial bio-nanocomposite films based on gelatin, tragacanth, and zinc oxide nanoparticles - Microstructural, mechanical, thermo-physical, and barrier properties.

Gelatin and tragacanth were employed to fabricate antimicrobial nanocomposites with 1, 3, and 5% zinc oxide nanoparticles (ZnO-NPs). FT-IR and XRD proved new chemical interactions among GEL/TGC/ZnO-NPs and higher crystallinity of nanocomposites, respectively. DSC showed a significant increase in melting point temperature (Tm) from ~ 90 to ~ 93-101 °C after adding 1-5% ZnO-NPs. Ultimate tensile strength (UTS) was remarkably increased to 31.21, 34.57, and 35.06 MPa, as well as Young's Modulus to 287.44, 335.47, and 367.04 MPa after incorporating 1, 3, and 5% ZnO-NPs. The ZnO-NPs dose-dependently reduced the water vapor permeability (WVP) of the films. FE-SEM analysis from surface and cross-section illustrated the compact and homogenous structure of the nanocomposites even up to 5% ZnO-NPs. The ZnO-NPs-containing nanocomposites had a good antimicrobial activity (~10-20 mm) against both Staphylococcus aureus and Escherichia coli. Generally, the results indicated that the prepared nanocomposite films are promising antimicrobial bio-materials for food packaging.

Nanotechnology in dentistry: Present and future perspectives on dental nanomaterials.

OBJECTIVES: The number of dental nanomaterials has increased significantly over the past years. A variety of commercial dental nanomaterials are available and researched. Nevertheless, how these nanomaterials work, what makes them special and whether they are superior to traditional dental materials is not always clear to dentists and researchers. The objective of this review paper is, therefore, to give an overview of the principles of nanomaterials and basic research and applications of dental nanomaterials. METHODS: The fundamentals of materials science of nanomaterials as well as their advantages and disadvantages are elaborated. The most important dental nanomaterials are discussed. This is mainly based on a survey of the literature and a review of the most frequently cited scientific papers in the international peer reviewed journal Dental Materials over the past five years. The developments of commercial dental nanomaterials as well as aspects of their clinical use are considered in this review. RESULTS: Nanomaterials have unique structures and properties that distinguish them from other materials. The journal Dental Materials is the journal with the highest numbers of articles and citations on the subject of dental nanomaterials. The most frequently reported dental nanomaterials are nanocomposites, nanoparticles, antimicrobial nanomaterials and bio-mineralization systems. Hallmarks of dental nanomaterials include a set of unique properties and challenges in the preparation of these materials. SIGNIFICANCE: By understanding the physical principles of dental nanomaterials, their strengths, limitations and their specific benefits will be better appreciated. Dental nanomaterials have potential for the future but currently do not always exhibit superior properties, for example in clinical situations.

Fabrication and characterization of a titanium dioxide (TiO2) nanoparticles reinforced bio-nanocomposite containing Miswak (Salvadora persica L.) extract - the antimicrobial, thermo-physical and barrier properties.

Objective: The microbial, physico-chemical and optical corruptions threaten a variety of foods and drugs and consequently the human biological safety and its accessible resources. The humanbeing's tendency towards bio-based materials and natural plant-extracts led to an increase in the usage of antimicrobial biocomposites based on medicinal herbs. Miswak (Salvadora persica L.) extract (SPE) has been proved effective for its antimicrobial and other biological activities. Therefore, in this study, titanium dioxide (TiO2) nanoparticles (TONP) and SPE were applied to fabricate antimicrobial carboxymethyl cellulose (Na-CMC) based bio-nanocomposites which would simultaneously promote some thermo-physical and barrier properties. Methods: CMC-neat film (C1), CMC/TONP-2% (C2) and CMC/TONP-2% with 150, 300 and 450 mg/mL SPE (SPE150, SPE30 and SPE450, respectively) were fabricated. The physical and mechanical properties; elemental mapping analysis (MAP), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA-DTG); fourier transform infrared (FTIR), energy-dispersive X-ray (EDX) and UV-vis spectroscopies were done to further validate the results. Results: Addition of TONP (2%) improved the blocking of UV light at 280 nm while SPE-containing nanocomposites completely blocked it. FTIR, XRD and SEM confirmed the formation of homogeneous films and high miscibility of applied materials. TONP led to an increase in Young's modulus (YM) and stress at break (SB) while SPE decreased them and enhanced the elongation to break (EB) (flexibility) of the active nanocomposites. Compared to CMC-film, the thermo-gravimetric analysis (TGA-DTG) showed a higher thermal stability for CMC/TONP and CMC/TONP/SPE nanocomposites. The EDX spectroscopy and elemental mapping analysis (MAP) proved the existence and well-distributedness of Na, K, Cl, S, Ti, F and N elements in SPE-activated nanocomposites. The pure SPE and SPE-activated nanocomposites showed a favorable antimicrobial activity against both gram-positive (Staphylococcus aureus) and negative (Escherichia coli) bacteria. Conclusion: The CMC-TiO2-SPE nanocomposites were homogeneously produced. Combination of TiO2 nanoparticles and dose-dependent SPE led to an improvement of thermal stability, and high potential in antimicrobial and UV-barrier properties. These results can generally highlight the role of the fabricated antimicrobial bio-nanocomposites as a based for different applications especially in food/drug packaging or coating.

A novel bioactive quaternized chitosan and its silver-containing nanocomposites as a potent antimicrobial wound dressing: Structural and biological properties.

Wound care is crucial for controlling infections of the injured area. Regarding this, wound dressings with antimicrobial activities are useful to minimize the microbial infections of the wounds. Herein, a series of quaternized chitosan nanocomposite films blended with silver nanoparticles were fabricated with high potential for wound dressing applications. After characterization of the prepared films by Fourier-transform infrared spectroscopy (FTIR), X-Ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and element mapping analysis (MAP). Other parameters such as swelling ratio, blood clotting activity, and biocompatibility of the films were also investigated. Besides, the antibacterial and antifungal activities of prepared samples were examined against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and a multi drug resistance Pseudomonas aeruginosa as a drug resistance bacterium strain. Interestingly, the designed quaternized chitosan film (even without silver nanoparticles) showed high antimicrobial activity against all tested microbial strains which is probably due to the presence of imidazolium moiety in the film matrix. Furthermore, all nanocomposites showed a potent antimicrobial activity. Generally, the results of cell proliferation and attachment with MTT assay and DAPI staining on HFFF cells, have proved the cytocompatibility nature of the nanocomposite films. These results indicate that the developed bioactive quaternized chitosan nanocomposite films can be considered as biomaterial for wound dressing applications.

Antimicrobial polyurethane thermosets based on undecylenic acid: synthesis and evaluation.

In the present study, plant oil-derived surface-modifiable polyurethane thermosets are presented. Polyol synthesis is carried out taking advantage of thiol-yne photopolymerization of undecylenic acid derivatives containing methyl ester or hydroxyl moieties. The prepared methyl ester-containing polyurethanes allow surface modification treatment to enhance their hydrophilicity and impart antimicrobial activity through the following two steps: i) grafting poly(propylene glycol) monoamine (Jeffamine M-600) via aminolysis and ii) Jeffamine M-600 layer complexation with iodine. The antimicrobial activity of the iodine-containing polyurethanes is demonstrated by its capacity to inhibit the growth of Staphylococcus aureus, and Candida albicans in agar media.