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ANTIBACTERIAL-COATED SURGICAL SUTURES BY ATOMIC LAYER DEPOSITION OF TITANIUM OXIDE DOPED WITH VANADIUM FOR THE TREATMENT OF THE SURGICAL SITE INFECTION
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Suture-associated surgical site infection causes bacterial pathogens to colonize the suture surface and biofilms that are highly resistant to antibiotic treatment. Surgical suture materials with antibacterial coating are becoming increasingly common in surgical practice. Traditional materials used in clinical settings often cause secondary complications such as infection, foreign body reaction, or chronic inflammation. Surgical sutures combining antibacterial nanomaterials possess a more promising efficacy. The application of antibacterial coatings to suture materials can make a significant contribution to prevention of the suture-associated surgical site infection. The most widely used and proven antimicrobial agent is the broad-spectrum antiseptic triclosan. However, due to the ecotoxicity of its oxidation products, there is currently a tendency to create suture materials with low or no triclosan content. This work provided a new approach to the development of antibacterial sutures based on the atomic layer deposition (ALD) technique. We have proposed applying a titanium–vanadium oxide nanofilm that is 12 nm thick on surgical sutures with an enhanced antibacterial property. The ALD process was carried out at a temperature of 80 °C. The ALD process was performed using supercycles consisting of repeated surface self-saturating hydrolysis reactions between TiCl4 and H2O, VOCl3 and H2O. The obtained surgical sutures showed high antibacterial effectiveness against strains of microorganisms E.Coli and S. Aureus. We are currently conducting animal tests.
The work was carried out within the framework of the State Assignment 1023022800054-7-3.4.4.

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Effect of mechanical and chemical process variation on antibacterial activity of polydopamine coating.

Low bacterial load and adhered biofilms are challenges to current tests and prophylactic measures, and can result in healthcare-associated infections (HAIs). It has been shown that the risk of HAIs can be reduced when antibacterial coatings are applied to the surface of medical devices. This study aims to optimize the antibacterial efficacy of polydopamine coating as a potential material for the prevention of HAIs.

Polydopamine coatings were characterized after varying the coating process. Modifications included the concentration of dopamine monomers, the sample position (horizontal vs vertical), the stirring speed (0 – 90 RPM) and the reaction time (0.5 – 24 h). The results were monitored via UV-visible, wettability and atomic force microscopy. The dopamine cytotoxicity was evaluated on the L929 cell line, in accordance with the ISO 10993-5 standard, and the antibacterial properties of polydopamine coatings were assessed using ISO 22196 standardization against Staphylococcus aureus and Escherichia coli.

Surface wettability, and therefore bacterial adhesion, are affected by the thickness and roughness of the polydopamine coating, playing a role in its antibacterial activity. Thicker and rough coatings had a better antibacterial effect against S. aureus (1.6 ± 0.4 log reduction), but not against E. coli (0.05 log reduction). The viability of L929 cells was ≥ 94 % in the presence of the polydopamine coating.

These results demonstrate that polydopamine is a promising non-toxic material for antibacterial coatings on medical devices. However, further tests are required to enhance its antibacterial properties.

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Development of smart polymer nanomaterials that generate nitric oxide forantibacterial application.

Introduction: Modern scientific and clinical data indicate that 60% of chronic wounds contain microbial biofilms, which are associated with the main pathophysiological processes and contribute to the prolongation of infection. The nitric oxide (NO) radical, depending on application time and concentration, has been shown to cause the dissolution of biofilms and sensitization of bacteria to antibiotics without causing resistance. In nanomolar concentrations, NO stimulates vasodilation, enhances the proliferation of endothelial cells, reduces thrombus formation, and promotes angiogenesis and wound healing. Therefore, research and development of the immobilization of nitric oxide precursors on carriers for local delivery of controlled amounts of NO for specific medical purposes is relevant.

Methods: The deposition of plasma polymers was carried out using a ZP-COVANCE-RFPE-3MP vacuum system equipped with an oil diffusion pump providing the residual pressure in a vacuum chamber below 30 Pa. Isopentyl nitrite (99.995%) and C2H4 (99.95%) were used as precursors to deposit thin films on silicon wafers and polycaprolactone nanofibers at a discharge power of 30 W. The obtained plasma-deposited polymer films were studied by SEM, EDX analysis, XPS, FTIR spectroscopy, and WCA. The films were tested against different pathogens.

Results: Plasma deposition resulted in homogeneous and well-bonded layers. SEM micrographs showed no pinholes, cracks, or other damage in the deposited layers. According to FTIR and XPS, the obtained spectra indicated the presence of nitroxyl compounds on the surface of samples. It was shown that nitroxyl-containing films prevented the formation of biofilms.

Conclusions: We developed an approach to deposit nitroxyl-containing films from a mixture of isopentyl nitrite/C2H4 and demonstrated antibacterial effects against Gram-positive and Gram-negative pathogens.

This work was supported by the Russian Science Foundation (grant №20-19- 00120-P).

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Development of antibacterial wound healing materials using polycaprolactone fibers and ZnO nanoparticles.

Introduction. Traditional dressings are inadequate for effective wound healing due to their restricted qualities; however, there is a growing global demand for wound treatment. The occurrence of problems in wound healing is primarily attributed to inflammatory processes triggered by infection with diverse microorganisms. This study involved the development of an antibacterial dressing using electroformed polycaprolactone (PCL) fibers that incorporated zinc oxide nanoparticles (ZnO NPs).

Materials and methods. The nanofibers were obtained in a mixture of acetic and formic acids with a concentration of PCL 25%. ZnO NPs, prepared by autoclave synthesis, were added to the acid mixture in varying amounts of 1, 3, and 5 wt.%. The structure and chemical composition of the ZnO NPs and PCL composite fibers were analyzed using SEM, EDX, and FTIR spectroscopy. The antibacterial activity was assessed against multiple strains of bacteria and fungus. The biocompatibility of the samples was assessed using the Lonza human dermal fibroblast cell line.

Results. The size of the produced ZnO NPs varied between 10 and 12 nanometers. The composite fibers have a size that varies between 300 nm and 1 µm. The EDX examination verifies that the primary constituents of the fibers consist of carbon, oxygen, and zinc. Furthermore, it is demonstrated that with an increase in the wt.% of ZnO, the atomic concentration likewise increases to 1.1%, 2.7%, and 3.9%, respectively. The successful implementation of ZnO nanoparticles was confirmed by the use of FTIR spectroscopy. The materials showed 100% antibacterial activity. When cell survival was evaluated, samples with 1% and 3% were shown to have low cytotoxicity in contrast to 5%.

Conclusions A novel composite fiber material with high potential for wound healing has been created. This platform exhibits enhanced bactericidal and proliferative activities. This study demonstrates the potential of utilizing the composite material in wound healing applications.
This research was funded by the Russian Science Foundation ( 20-19-00120-P).

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Development of nanocapillary electrochemical biosensors for glucose detection

This work considers the possibility of the fabrication of a nanocapillary electrochemical biosensor for glucose determination. The principle of glucose determination is based on the reaction of glucose decomposition into glucolactone and hydrogen peroxide. Glucose oxidase is used as an enzyme. Electrodes based on glass nanocapillaries are used as biosensors for the determination of various analytes due to their ease of fabrication, high sensitivity, selectivity and small size.

Before the fabrication of the nanocapillary sensor, the technique of enzyme immobilization on the mica surface was reproduced. Freshly pierced mica sheets were silanized with 0.33% APS diluted in water and ethanol. The silanized mica was washed in distilled water and immersed for 12 h in 2.5% GA solution in PBS, then washed with distilled water and dried under an Ar atmosphere. The mica samples were then immersed in GOx in PBS solution (2 mg/mL) overnight at room temperature. At each modification step, the surface topography was examined via AFM. Evaluation of the surface topography showed that irregularities in the topography appear during the enzyme immobilization process, which change as the mica surface is modified.

This technique was reproduced to functionalize the inner surface of the nanopipette. At each modification step, cyclic voltammetry waveforms were recorded in HBSS from -800 to 800 mV (400 mV/s) relative to Ag/AgCl. After the reaction of quartz with APS, terminal amino groups were formed on the surface and protonated in the electrolyte solution, and the ionic current at positive potentials increased significantly. Upon crosslinking with glutaric aldehyde, the ionic current decreased as the carbonyl groups were bound to the positively charged groups of APS. After functionalization with glucose oxidase, cyclic voltammetry showed the negative rectification of the current as GOx contains a negative charge.

Conclusion: The possibility of immobilizing glucose oxidase on the nanocapillary surface for glucose detection was demonstrated.

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Synthesis and Characterization of Mesoporous Silica Nanoparticles for Delivery of Anticancer Drugs

Mesoporous silica nanoparticles (MSN) are a promising drug delivery system due to their unique morphology, tunable particle size (50–300 nm), controlled pore size, high surface area, and biocompatibility. The use of MSN as carriers can improve the effectiveness of anticancer drugs by targeted delivery to the tumor, controlled release, and reduced side effects. Currently, the possibility of delivery of such classes of anticancer drugs as cytostatics, photosensitizers, and radiopharmaceuticals using MSN is being actively studied.

The aim of this work is to synthesize and evaluate the morphology of MSN.

The research objectives were to obtain mesoporous nanoparticles, to estimate their size, to measure the specific surface area of the particles, to analyze the adsorption capacity of the particles, the efficiency of encapsulation, and the release kinetics of the drug.

MSN were synthesized by the modified Stober method, in which tetraethoxysilane is the source of silicon, and the nanoparticles are obtained by using the CTAB surfactant. The particle size analysis was carried out by scanning electron microscopy, and the specific surface area of the particles was also estimated by the BET method. The loading and release kinetics of doxorubicin from MSN were studied spectrophotometrically using a Varioscаn LUX multifunction plate reader daily for 20 days. Doxorubicin fluorescence was measured at an excitation wavelength of 470 nm and an emission wavelength of 590 nm. The release kinetics of doxorubicin were studied at room temperature in phosphate-buffered saline (PBS) with pH 7.4.

As a result, the average particle size of MSN was 100 nm, and the pore diameter was 3 nm. The specific surface area of MSN was 644 m2/g. Doxorubicin loading was carried out by adsorption from a solution with a concentration of 2 μg/ml. The doxorubicin loading efficiency was 19,13%

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Spinach-Mediated Synthesis of Silver Nanoparticles/Nanoclusters and Fabrication of Reuseable Polymer Beads and Membranes for
Antimicrobial and Photocatalytic Applications

Recently, the phytosynthesis of metallic nanoparticles using extracts of plants and plant products has gained considerable importance in biomedical applications due to its environmentally friendly approach. In this study, we developed stable silver nanoparticles and silver nanoclusters using the extract of green spinach as a chemical reducing and stabilizing agent. Upon the addition of the extract to a silver nitrate solution, silver nanoparticles formed immediately, as evidenced by a color change in the solution. A characteristic surface plasmon resonance peak at around 400 nm confirmed the formation of silver nanoparticles.

The silver nanoparticles were encapsulated in alginate beads through a single-step method involving ionotropic crosslinking using calcium chloride (5 wt%). The resulting beads were compact and black in color. The beads were porous and contained plate-like silver nanoclusters, as revealed by Scanning Electron Microscopy studies. The photocatalytic characteristics of the beads were evaluated using two important organic molecules/pollutants, namely 2-nitrophenol and methyl orange. The beads exhibited excellent photocatalytic properties by degrading the pollutants into non-toxic substances in less than 30 minutes. The enhanced degradation performance was attributed to the synergistic effects of silver nanoclusters and alginate. The nanoclusters acted as catalytic sites for the degradation process, while alginate provided a stable matrix for the immobilization of the nanoclusters and facilitated the mass transfer of the pollutants to the catalytic sites. This study highlights the effectiveness of silver nanocluster-loaded alginate beads as a promising and eco-friendly material for the treatment of medical waste in the future.

Reuseable polymer films of alginate and polyvinyl alcohol containing silver nanoparticles were also developed using a spray method. The films were robust and exhibited excellent antibacterial properties against various strains of bacteria. This research project paves the way for the development of sustainable and effective nanomaterial-based solutions for biomedical and environmental remediation.

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The impact of binary bioglass on the biodegradation and bio-mineralization of PCL electrospun fibers for guided bone regeneration

In this study, we produced Poly(ε-caprolactone) (PCL) electrospun fibers with varying concentrations (5%, 10%, 15%, and 20% wt. %) of binary bioactive glass 63S-37C (BG, 63% SiO2 - 37% CaO). These membranes showed good acellular bioactivity, biocompatibility, and reasonable biodegradability. Apatite formation in SBF was assessed using SEM-EDS analysis, indicating enhanced bioactivity with increased BG content. We also examined the effects of BG incorporation on membrane morphology, composition, fiber diameters, biodegradability, and bioactivity. Our findings demonstrate well-dispersed BG within the PCL matrix, maintaining thermal stability. Although PCL membranes were more hydrophobic than BG-filled ones, PCL/BG membranes displayed improved degradability, wettability, and enhanced apatite formation, especially with higher BG concentrations (10% and 20% wt. %). These results suggest that PCL/BG membranes hold promise for guided bone regeneration.

We focused on developing guided bone regeneration (GBR) membranes with enhanced bioactivity, biocompatibility, and proper degradation ability. By incorporating binary bioactive glass "63% SiO2 - 37% CaO" produced via a hydrothermal method into Poly(ε-caprolactone) (PCL) electrospun membranes, we aim to investigate their properties. The membranes aim to isolate bone defects from surrounding soft tissue, promoting bone tissue growth while preventing interference from non-osteogenic tissues. The impact of bioactive glass content on membrane properties, including wettability, biodegradation, and bio-mineralization, is examined to assess their potential applications in biomedical fields, particularly for guided bone regeneration.

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Nanocellulose reinforced polyacrylamide/sodium alginate double crosslinked network composite hydrogels: Mechanical behaviour and FEM analysis

For many load bearing biomedical applications, development of mechanically strong hydrogels are needed to act as supporting structures. Due to their extreme strength and toughness, Double-network (DN) composite hydrogels have emerged as a hot research topic. Herein, we prepared cellulose nanofiber (CNF) reinforced poly(acrylamide-co-Alginate) (P(AAm-co-Alg)) double network composite hydrogel via in situ polymerization. Based on the double-network P(AAm-co-Alg)/CNF-Fe3+ composite hydrogel structure formed by the covalently cross-linked acrylamide network and non-covalently COO−-Fe3+ ionic coordination act as a secondary crosslinking network. The development of Cellulose nanofibril (CNF) and Fe3+-based anisotropic functional tough composite hydrogel construct, presenting the development and physical characterisation (shape morphing, swelling potential and rheology) of the composite structure. By incorporating CNF and Fe3+, the tensile properties such as tensile strength and toughness of the P(AAm-co-Alg) composite hydrogel were improved by 300% and 250%, respectively. The loading of FE3+ also enhanced the energy dissipation in loading and unloading tests.

Here, we also proposed the 3D printed multilayer composites, printed in nature inspire hierarchical laminate fashion, to fabricate a functional porous composite construct. We implement the finite element (FE) modelling to analysis the pre-programmed anisotropic functional composite structure with the computer simulation. It shows how the improved physical, mechanical and biological functionality of the hydrogel fiber reinforced composite printed scaffold can be programmed by varying cellulose fibers/fibrils orientation and matrix compliance, making it suitable for load-bearing biomedical applications. Our novel design approach, based on DN composite hydrogel with enhanced anisotropic mechanical, physical and antibacterial properties of the printed construct, offers new perspectives for application in the area of electronic skin,, drug delivery and tissue engineering.

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ATRP-Synthesized Linear Copolymer Conjugates from Pharmaceutically Functionalized Choline Ionic Liquid Monomers for Ampicillin Delivery

Introduction: Linear polymer drug delivery through ATRP (atom transfer radical polymerization) stands as a breakthrough in medical science, offering exceptional advantages. The controlled and predictable structure of linear polymers ensures precisely regulated drug release, optimizing therapeutic outcomes. This method allows for tailored drug delivery, enabling the targeting of specific cells or tissues with minimal side effects.

Methods: This study involved the synthesis of monomeric ionic liquids by substituting the chloride counterion in [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA/Cl) with the ampicillin anion from its sodium salt (AMPNa), resulting in the formation of [2-(methacryloyloxy)ethyl]trimethylammonium ampicillin (TMAMA/AMP). Subsequently, methyl methacrylate (MMA) was copolymerized with TMAMA/AMP using the ATRP method, producing copolymers based on AMP, denoted as P(TMAMA/AMP-co-MMA). The drug release mechanism was facilitated by ion exchange with phosphate anions in PBS, mimicking the natural environment of physiological fluids with a pH of 3.7 at 37°C.

Results: The drug carriers exhibited 61–76% of the AMP contents in the copolymers. The polymeric chain lengths were determined by assessing the total monomer conversion (27–47%), leading to a degree of polymerization (DPn = 131-363). Utilizing dynamic light scattering (DLS), the hydrodynamic diameters (Dh = 190–328 nm) of polymer nanoparticles and their polydispersity index (PDI = 0.01-0.06) in an aqueous solution were determined. In addition, in vitro studies demonstrated the release of 72–100% (11.1–19.5 µg/mL) of drug within 26 hours.

Conclusion: Our study explored the well-defined linear copolymers, P(TMAMA/AMP-co-MMA)s, with varying ionic contents, showcasing their promise as carriers in drug delivery systems (DDS). The findings affirm the efficacy of the trimethylammonium-based IL monomer carrying AMP in designing polymeric carriers with precise amounts of therapeutically active anion. This DDS holds potential for preventing and treating diverse bacterial infections, including respiratory tract infections.

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