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In silico model of CoCr stent performance in multi-layered arteries using two-way fluid–structure interaction: influence of boundary conditions and vessel length
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The qualitative and rapid assessment of atherosclerotic lesions is still a challenging task. The primary therapy for this pathology involves implanting coronary stents, which help restore blood flow in atherosclerosis-prone arteries. In-stent restenosis is a stenting procedure complication detected in about 10-40% of patients. A numerical study using two-way fluid–solid interaction (FSI) assessed the effectiveness of stenting and was able to reduce the number of complications. Nevertheless, the boundary conditions (BCs) used in the simulation play a crucial role in the implementation of an adequate computational analysis. Three CoCr stent designs were modeled with the suggested approach. The artery–plaque system was modeled as a multi-layer structure with anisotropic hyperelastic mechanical properties. Two kinds of boundary conditions for the solid domain were examined—fixed support (FS) and remote displacement (RD)—to assess their impact on hemodynamic parameters to predict restenosis. Additionally, the influence of artery elongation (short-artery model vs. long-artery model) on the numerical results with the FS boundary conditions was analyzed. A comparison of the FS and RD boundary conditions demonstrated that the variation in the hemodynamic parameter values did not exceed 2%. An analysis of the short-artery and long-artery models revealed that the difference in hemodynamic parameters was less than 5.1%, and in most cases, it did not exceed 2.5%. The RD boundary conditions were found to reduce the computation time by up to 1.7–2.0 times compared to the FS boundary conditions. This study revealed that the stent design significantly affected hemodynamic parameters as restenosis predictors. Moreover, the stress–strain state of the artery–plaque–stent system also depends on the proper choice of boundary conditions.

The authors thank the Ministry of Science and Higher Education of the Russian Federation for their financial assistance within the framework of the state assignment for 18 performing fundamental scientific research (FSNM-2023-0003 project).

  • Open access
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Chitosan Nanoparticle-Loaded Essential Oils Electrosprayed onto Polycaprolactone Microfibers: A Novel Antifungal Therapy for Diabetic Foot Ulcers

Diabetic foot ulcers (DFUs) represent a significant healthcare challenge due to their susceptibility to fungal infections, which can exacerbate the already compromised healing process and limit treatment strategies. Here, we present a novel approach based on chitosan (Ch) nanoparticles loaded with commercial essential oils (EOs; citral, geraniol and cinnamaldehyde) and electrosprayed onto polycaprolactone (PCL) electrospun microfibers. The combination of chitosan, known for its antimicrobial properties and biocompatibility, with EOs possessing potent antifungal activity, offers a promising strategy for enhanced therapeutic efficacy. The electrospraying technique facilitates the uniform distribution of Ch nanoparticle-embedded EOs onto PCL microfibers, ensuring controlled release and prolonged retention at the wound site. Chitosan nanoparticles were synthesized using a specific 2.5:1 ratio of Ch-Sodium triphosphate (TPP) and Tween 80 as a surfactant, and loaded with the EOs known for their potent antifungal properties. Subsequently, these nanoparticles were dispersed onto PCL fibers using the electrospraying technique. The resulting composite material exhibited excellent antifungal efficacy against common fungal pathogens implicated in DFUs, namely Candida spp. Moreover, the synergistic effect of Ch, EOs, and PCL provided sustained release of the bioactive compounds, prolonging the antifungal effect. Data confirmed this innovative approach as a promising strategy for combating fungal infections in DFUs, potentially improving clinical outcomes and quality of life in diabetic patients.

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Physicochemical study of mucoadhesive polymers and their interactions with mucin

Solid drug dosage forms applied directly to the mucous membrane are becoming very popular because they allow to prolong the drug release for several hours and ensure maintainance of the optimal therapeutic level. This effect is possible due to the presence of mucoadhesive polymers. The mutual entanglement of polymer and mucin chains leads to form a gel structure which is a reservoir for the drug. Generally, the mucoadhesive forms contain hydrophilic polymers, such as polycarbophil, carbomer, chitosan, or cellulose derivatives (HPMC, HEC, etc.).

Scientific papers indicate that selecting the appropriate ratio of the polymers can extend the drug release, enhance the repeatability of the release profiles, improve the mucoadhesive properties of the material surface, and improve drug transport to the mucosa. Therefore, it is important to look for a correlation between the composition of the mucoadhesive carrier and its surface properties. Consequently, the wettability of polymer matrices, the degree of their swelling, the SFE value, and the mucoadhesion force are crucial for designing oral carriers and predicting their effectiveness in vivo. In our research, we measured the swelling and the contact angle on the polymer surface by the sessile drop method using various simulated biological fluids, water, and diiodomethane. The correlation between the physicochemical properties and release profiles obtained for antifungal drugs were evaluated.

Moreover, to explore the interactions between the polymer and mucin in the cell membrane environment, studies were carried out using the Langmuir monolayer technique. The obtained results allowed to better understand the mucoadhesion process and confirm the existence of interactions between mucin, mucoadhesive polymers, and model biological membranes. We have shown that these interactions depend on the type of mucoadhesive polymers, pH, and presence of mucin.

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The Influence of Aortic Valve Leaflet Material Models on Hemodynamic Features in Healthy and Pathological States
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Cardiac blood outflow restriction is caused by calcific aortic stenosis, a gradual thickening of the aortic valve leaflets, and long-term fiber tissue remodeling. Surgeons have several options when replacing an aortic valve: they can employ minimally invasive techniques like transcatheter aortic valve implantation (TAVI) or perform open-heart surgery, which requires making an incision in the chest. There are several benefits and drawbacks to these kinds of surgeries. The Ozaki procedure, which replaces the aortic valve with tissue from an autologous pericardium, has been proposed recently. Although this approach shows promise in treating aortic valve disease, it lacks long-term outcomes and appropriate leaflet sizing selection. Surgeons can anticipate the results of each patient's operation with the use of numerical fluid simulations.

However, a question remains unanswered in the explanation of material models for leaflet mechanics. It can be challenging to choose the best model to explain various aortic valve diseases. We analyzed aortic valve leaflet material models numerically using 3D FSI simulation in order to characterize the hemodynamics in diseased, normal, and Ozaki situations. Furthermore, we disclose the displacement distributions, von Mises stress, and wall shear stress. We analyzed the isotropic hyperelastic model, the anisotropic hyperelastic model, and the elastic model in this study. Velocity, pressure, OSI, and TAWSS were also evaluated. We discovered that the proper model for leaflet simulation in the Ozaki case and the healthy state case involves the Holzapfel–Gasser–Ogden constitutive equation. In the case of pathology (calcification), it is better to adopt the elastic model.

The authors thank the Ministry of Science and Higher Education of the Russian Federation for their financial assistance within the framework of the state assignment for performing fundamental scientific research (FSNM-2023-0003 project).

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Bactericidal coatings based on elastomers.

The rapid evolution of medical device technologies has provided effective solutions to several health challenges, ranging from artificial heart valves to hip replacement prostheses. Despite advancements in medical device technologies, infections remain a critical concern, posing risks such as tissue damage and organ failure. To address this, biomaterials with enhanced bactericidal properties are crucial.

This study examined the effectiveness of the produced elastomeric coatings containing bactericidal additives, in preventing bacterial infections on the surfaces of materials used in medicine. The influence of various additives, including silver, turmeric, graphene, cloves, and black cumin seeds, was tested on the bactericidal properties of silicone coatings. The bactericidal tests carried out showed an effect dependent on their concentration, and samples containing silver and black cumin seeds showed the strongest bactericidal properties. However, optimal concentrations must balance bactericidal effectiveness with potential cytotoxicity concerns. The material tests carried out focused on understanding the impact of additives such as silver, turmeric, graphene and cloves on the properties of the elastomer, revealing their diverse impact on the chemical structure, surface morphology, hardness, and hydrophobicity. The analysis of the surface adhesion of polymer coatings to glass proved that the use of additives improves their adhesion to the substrate used. The strongest effect was visible when turmeric was added to the silicone matrix.

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3D-Printed Nanocomposite Scaffolds for Bone Tissue Regeneration

Three-dimensional (3D) printing technology has revolutionized the field of tissue engineering, particularly in the development of scaffolds for craniomaxillofacial (CMF) bone regeneration. Till today, a question remains regarding the use of 3D-printed nanocomposite scaffolds incorporating metallic or gold nanoparticles for craniomaxillofacial bone regeneration. In this research study, we aim to develop 3D-printed nanocomposite scaffolds tailored with various bioactive materials and nanotechnologies, offering a significant advancement in the field of CMF bone regeneration. Gelatin methacryloyl (GelMA) was selected as a bioink candidate for its biocompatibility and tunable mechanical properties. Surface-engineered gold nanoparticles (AuNPs) were incorporated to enhance the rheological properties, conductivity, and printability of the bioink. The integration of bioactive molecules, such as small-chain amino acids conjugated to gold nanoparticles (AuNPs), had the potential to contribute to bone healing and regeneration. The improvements in biological, electrical, and rheological characteristics facilitated enhanced differentiation of encapsulated stem cells and enabled the fabrication of highly viable and stable constructs. These findings hold significant potential to advance 3D bioprinting capabilities, offering a promising avenue for the fabrication of precise and biologically relevant tissue constructs for applications in regenerative medicine and personalized therapeutic interventions. These scaffolds can be customized to the specific needs of the defect site, thereby improving the outcomes of bone regeneration therapies.

  • Open access
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Universal drug delivery platform for anticancer theranostics based on dumbbell-like Fe3O4-Au nanoparticles

Anticancer therapy is a significant challenge today. The use of nanocarriers as a promising method can influence the pharmacokinetics and biodistribution of drugs, as well as reduce side effects. Combinations of drugs such as doxorubicin and paclitaxel in certain ratios have been shown to exhibit a synergistic effect, while using drugs simultaneously can reduce the development of resistance and the total administered dose. However, delivering combinations of drugs to tumor cells at a given molar ratio is difficult due to differences in the chemical structure and properties of anticancer drugs (hydrophobicity and charge). In this work, magnetic dumbbell-like Fe3O4-Au nanoparticles (MDNPs) are proposed. Firstly, due to their magnetic properties, MDNPs can be used for magneto-resonance imaging. Secondly, the presence of two chemical surfaces (Fe3O4 and Au) allows us to modify MDNPs with different molecules in order to load two different types of drugs at given ratios. MDNPs were produced through the thermal decomposition of Fe(CO)5 and HAuCl4 in octadecene-1. The size was 14±1 nm for Fe3O4 and 4±1 nm for Au. After that, the Fe3O4 surface of the MDNPs was sequentially coated with 3,4-hydroxyphenylacetic acid, FAM-maleimide modified human serum albumin (HSA), and NH2-PEG-COOH. These nanoparticles were stable in both water and PBS for 30 days and allowed for the loading of cisplatin (cPt, 0,3mg/1mg Fe), doxorubicin (DOX, 0,45mg/1mg Fe), and paclitaxel (PTX, 0,35mg/1mg Fe). The Au surface was modified with HSA that had previously been loaded with a drug to obtain a system with two drugs. As a result, two systems were produced (MDNP-cPt-DOX, with a molar ratio of cPt/DOX 1:1, and MDNP-PTX-DOX, with a molar ratio of PTX/DOX: 1:3). These proved to be comparable with free drugs' synergistic results in terms of their toxicity against the CT26 cell line. To summarize, modified MDNPs can be loaded with different types of drugs, and the Au surface allows for the addition of another drug to achieve a synergistic effect in therapy.

  • Open access
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Mechanical and biological assessments of braided artificial tendons functionalized with cork extract.

The incidence of tendon ruptures has increased over the years, and represents one of the main causes of musculoskeletal injuries that occur annually due to high mechanical loads, degenerative processes, trauma, stretching, chronic overuse, inflammation, etc. In this investigation, a new approach using braids of different materials, namely biodegradable (lyocell and biodegradable polyester) and non-biodegradable (polyethylene terephthalate (PET)) materials functionalized with natural cork extract was explored. The cork extract was selected due to its biocompatibility and its properties of interest (antioxidants, antimicrobials, anti-inflammatory, antifungals, cell affinity, etc.). The mechanical characterization of the braids was carried out, and lyocell presented properties closer to accepted ranges: extension less than 10%, and tensile strength between 19 and 100 MPa. Loading of the cork extract into the bradding systems was evaluated in three ways: (1) dip coating; (2) surface activation with UV light followed by dip coating; and (3) binding through dopamine coating. The cork extract was found effective in preventing bacterial action and in promoting antioxidant activity. Collected data deemed the proposed strategy as promising for treating tendon lesions, thus improving the quality of life of affected patients. This innovative approach has the potential to revolutionize existing treatment methods, offering solutions for patients with tendon injuries.

  • Open access
  • 25 Reads
NANOSCALE CYCLODEXTRIN SYSTEMS FOR THE DELIVERY OF TETRAPYRROLE PHOTOSENSITIZERS
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Introduction. Application of pharmacological forms based on nanomaterials is a promising methodological approach to increase the therapeutic efficacy of nonpolar drugs by increasing their bioavailability. One of the most important parameters that makes it possible to assess the effectiveness of the use of pharmacological forms is the release profile of the drug from the nanocarrier. The role of the kinetic characteristics of drug liberation from nanocarriers has not been sufficiently studied due to the existing limitations of the analysis of mass transfer in complex biological systems.

The aim of this work is to compare the equilibrium and kinetic characteristics of the distribution of the photosensitizer Temoporfin when the photosensitizer is bound to monomeric or polymeric forms of β-cyclodextrin derivatives.

Materials. Temoporfin was provided by Biolitec® (Germany). The cyclodextrin methyl-β-cyclodextrin was purchased from AraChem (Netherlands). β-cyclodextrin polymer and carboxymethyl-β-cyclodextrin were purchased from Cyclolab (Hungary).

Results. The fluorescence features of Temoporfin in complexes with β-cyclodextrin derivatives were studied, and the binding constants were determined. According to the results obtained, all cyclodextrin derivatives exhibit a high affinity for the sensitizer. Using the developed spectral techniques, the kinetics of Temoporfin release from complexes with cyclodextrins in the presence of model biological membranes or serum proteins were analyzed. The processes of association and dissociation of photosensitizer molecules from nanocarriers strongly depend on both the physicochemical properties of cyclodextrin molecules and their structure. Despite their lower affinity, polymeric cyclodextrins are able to delay sensitizer molecules for a significantly longer period of time.

Conclusions. Our results show that fluorescent techniques are highly informative in studying the processes of sensitizer redistribution between nanostructures. According to the data obtained, the rate of drug release from complexes with nanomaterials varies in a wide range, which should be taken into account when analyzing the pharmacokinetics of drugs introduced as part of complexes with a nanocarrier.

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Metal complexes of a naturally inspired framework functionalized for antibacterial biomaterials development

In the realm of combating antimicrobial resistance (AMR) and tackling infections triggered by priority pathogens outlined in the ESKAPE acronym by WHO, the development of innovative antibacterial biomaterials through novel multifunctional rhenium and iridium flavonoid complexes holds significant promise. In the MET-EFFECT project (funded MSCA-SE, Horizon Europe, https://met-effect.com) groundbreaking concept of using novel multifunctional rhenium and iridium flavonoid complexes as both metallodrugs and homogeneous catalysts is proposed. By leveraging the synergistic potential of these complexes, which act both as metallodrugs and homogeneous catalysts, advanced solutions for countering ESKAPE pathogen infections can be crafted. These biomaterials represent a beacon of hope in addressing the pressing challenges posed by antimicrobial resistance, thus bolstering patient outcomes within healthcare environments. Integration of rhenium and iridium flavonoid complexes into composite biomaterials, such as hydrogels, films, or coatings, stands as a pivotal strategy for antimicrobial applications. Within these biomaterial matrices, these complexes serve dual roles as both antimicrobial agents and catalysts, effectively combating infections brought about by ESKAPE pathogens. By incorporating flavonoid ligands renowned for their antimicrobial properties, such complexes disrupt bacterial cell membranes or impede crucial metabolic pathways, ultimately leading to bacterial demise. Furthermore, these multifunctional complexes can be tailored to selectively target specific bacterial species within the ESKAPE group, such as Staphylococcus aureus or Klebsiella pneumoniae, while mitigating adverse effects on commensal bacteria or host cells. This targeted approach significantly enhances the efficacy and safety profile of the metallodrugs. Emphasis on the design of antibacterial biomaterials incorporating rhenium and iridium complexes prioritizes biocompatibility and safety. Formulations are meticulously optimized to minimize cytotoxicity and immunogenicity, thereby ensuring seamless compatibility with host tissues and cells.

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