Introduction: Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers and is prevalent among younger women. Due to the lack of specific receptors, treatment options are limited. Metastatic TNBC has a dismal prognosis with an overall survival rate of only 13 months due to drug resistance. Thus, there is an urgent need for new drug delivery systems to improve the therapeutic modality of TNBC. We have synthesized carbon quantum dots (CQDs) from biowaste, leveraging anti-proliferative effects on TNBC cells.

Methods: CQDs were synthesized by a hydrothermal process from garlic peel and mango leaves in a 1:1 proportion using a stainless-steel autoclave lined with poly(tetrafluoroethylene) (PTFE), heated at 180 °C for 4h under autogenous pressure and filtered. The obtained filtrate was sonicated for 2h and dried in a hot-air oven to produce CQDs. A morphological evaluation and MTT assay of CQD on NIH3T3, MCF7, and MDA MB 231 cells were performed.

Results and Discussion: The microscopic evaluation of NIH3T3 cells exhibited no morphological changes up to 500 µg/ml, whereas MCF7 and MDA MB 231 cells showed morphological changes from concentrations of 100 µg/mL and 50 µg/mL, respectively. Moreover, the MTT assay revealed increased cytotoxicity from day 3 onwards in both the cell lines, more significantly in MDA MB 231.

Conclusions: The CQDs synthesized using biowaste are biocompatible with non-cancerous NIH3T3 cells, whereas they exhibit anticancer activity on breast cancer cell line MCF7 and triple-negative breast cancer cells MDA MB 231. Hence these CQDs can extend the arsenal of functional anti-cancer materials for the targeted therapy of TNBC suffering patients.

Introduction: 3D printing, or additive manufacturing, is a modern technique for creating three-dimensional physical objects. It is used in reconstructive medicine and requires the use of new materials. Among biodegradable polymers, polyhydroxyalkanoates (PHAs) are prominent. They benefit from direct fermentation, which does not require complex technological stages like polylactide and polycaprolactone. Varying the substrate or producer strain allows polymers with different properties to be obtained.

Methods: First, the filament was obtained through the extrusion of P(3HB-co-3HV). For printing, we used FDM technology on a 3D printer with the author’s blowing system. This made it possible to reduce thermal deformation when creating cylindrical scaffolds with a diameter of 13 mm, a height of 4 mm, and a porosity of 65%.

To study biological compatibility, light and fluorescence microscopy were used, as well as an MTT test on a culture of NIH 3T3 mouse fibroblasts.

The implantation of 3D scaffolds was studied on a model of segmental osteotomy of the tibia in two pigs. In each animal, a bone cavity for implantation was formed in the central part of the femoral diaphysis. After the operation, the animals were monitored, measuring body temperature, heart rate, and respiration. This study was conducted ethically and with humane treatment of animals.

The statistical analysis of the results was carried out using traditional methods, with data presented as the mean ± error for 95% confidence intervals.

Results and Conclusions: The results showed the high biocompatibility of the scaffolds: microscopy, fluorescent staining, and the MTT test confirmed their complete filling with cells, which maintained their metabolic activity for up to 10 days.

Histological and X-ray analyzses showed complete healing of the defect within 5 months. These findings suggest that the designed absorbable 3D scaffolds are promising for use in bone grafting.

Introduction
Mangiferin is a non-toxic bioactive substance with antioxidant, anti-inflammatory, antimicrobial, anticancer, and immunomodulatory activities. However, it has poor water solubility, and the use of mangiferin is hindered. Biopolymer matrixes, e.g. in nanofibrous form, could be applied to increase the bioavailability of loaded mangiferin. Hyaluronic acid (HA) is one of the attractive biopolymers for such nanofibers. In addition to biocompatibility and biodegradability of HA, the presence of its specific cell receptors (mainly, CD44) allows providing the targeted delivery action.

Methods
High molecular HA was used as a polymer matrix for mangiferin-loaded nanofibers. Electrospinning parameters: 28 kV, flow rate 2 mL/h, distance between electrodes 140 mm. Methods and software: SEM (morphological analysis), UV–VIS spectrophotometry (mangiferin release into PBS with pH = 7.4), ImageJ (statistical analysis), OriginPro (visualization and kinetic model definition).

Results and discussion
The minimum diameter, average diameter, and range of blank HA nanofibers are equal to 107 nm, 252 nm, and 291 nm, respectively. With mangiferin concentration increase, the above-mentioned characteristics increase up to 152 nm, 291 nm, and 398 nm, respectively. Thus, the slight diameter distribution extension is detected. Mangiferin release has an anomalous (non-Fickian) transport mechanism. It is expected that due to the natural origin and non-toxicity of the initial components, the obtained nanofibers could be characterized as nonhazardous and biocompatible material, and after additional investigations, including in vitro and in vivo analysis, they could be recommended for burn and wound regenerative coatings and transdermal delivery systems. Cross-linking is recommended for tuning the controlled release rate.

Conclusions
Thus, the obtained results can be used in the further development and improvement of delivery systems with mangiferin. The authors are planning to continue this research and to analyze the toxicity, efficacy, and mechanism of targeting action.

This research was funded by the Russian Science Foundation, project number 24-23-00269. Link to information about project: https://rscf.ru/en/project/24-23-00269/

Introduction: Alginate-based hydrogel films are widely used as wound dressings. Probiotic lactic acid bacteria, particularly lactobacilli and bifidobacteria, are promising therapeutic agents for wound dressings due to their antagonistic action against wound infection pathogens, potentially through competitive exclusion and the production of antimicrobial compounds. The aim of this study was to address the challenges encountered in the development of probiotic-loaded hydrogel wound dressings, namely, the loss of antibacterial substances during the immobilization, reduced cell viability, and deterioration of the films' mechanical properties during storage.

Methods: Probiotic lactic acid bacteria (Lactobacillus bulgaricus and Bifidobacterium bifidum) were immobilized in alginate-based hydrogel supplemented with pectin or starch. Films were cultured in Blaurock medium for 2-6 days, saturated with cryoprotectants (glycerol or DMSO) at 5-20% concentration, and stored at various temperatures (+25°C to -80°C) for 7 days. The efficiency of bacterial immobilization, viable cell count, and antagonistic activity against wound infection pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli) were evaluated.

Results and Discussion: Bacterial cells were immobilized by spraying calcium chloride on a cell suspension in sodium alginate. Pectin or starch addition significantly improved the films' mechanical properties. Culturing films with immobilized bacteria for 2 days resulted in a 100-fold increase in viable cell count and the acquisition of antagonistic properties against wound infection pathogens. Optimal cryoprotectant concentrations were established, and the films with immobilized bacteria maintained their key properties after low-temperature storage.

Conclusions: A protocol for obtaining alginate-based hydrogel films supplemented with pectin or starch for the immobilization, cultivation, and low-temperature storage of lactic acid bacteria was developed. The films exhibited high antagonistic activity against major wound pathogens, suggesting their potential application as wound dressings for treating infectious wounds.

Introduction: The development of theranostic systems could improve the quality of cancer treatment. Biocompatible Fe3O4 nanoparticles can be used in contrast agents and hyperthermia preparations. Doxorubicin (DOX) is the antitumor agent in the system. However, the surface modification of the developed systems is necessary for safe and prolonged circulation in the bloodstream. This study compared the influence of polymer shell composition on DOX release and particle stability in a saline solution. We analyzed polymers such as chitosan, polyethylene glycol (steric hindrance), and lysozyme.

Methods: We prepared Fe3O4 nanoparticles using the hydrothermal method. The synthesized particles were examined using SEM, EDX, FTIR, and BET analysis systems. The magnetic characteristics and surface charge of the nanoparticles were also studied. DOX loading and release were investigated using spectrophotometric methods at different pH values (5.5, 7.4, and 8.5). The coating techniques of the developed systems with polymer shells were optimized. The DOX release kinetics of coated particles at different pHs were investigated. Polymer-coated particles provide pH-dependent drug release due to the swelling–shrinking behavior of polymers. The cytotoxicity of the obtained systems was evaluated through in vitro tests using the cancer Emt6 cell line and the NIH 3T3 healthy cell line.

Results: The obtained nanoparticles (20 nm) were superparamagnetic. We determined the DOX loading capacity of the particles to be 15%. The particles demonstrated a high percentage of drug release (80%) at pH=5.5, whereas drug release was nearly absent in neutral and alkaline solutions. All types of polymer coatings provided particle stability and prolonged drug release. The chitosan shell demonstrated the highest colloidal stability, while the largest release rate (40%) was shown by lysozyme. Fe3O4 particles loaded with doxorubicin exhibited cytotoxicity to both cell lines, but the coating application reduced the cytotoxic effect on healthy cells.

This research was funded by the Russian Science Foundation (№20-19-00120_P).

Polyhydroxyalkanoates (PHAs) belong to a class of polyesters of natural origin obtained by microbiological synthesis. Despite good mechanical properties, biodegradation, and biocompatibility, PHAs are hydrophobic biopolymers, so the introduction of hydrophilic materials plays an important role, allowing them to influence the properties of the resulting microparticles. The goal of this work was to obtain microparticles from poly-3-hydroxybutyrate (P3HB) in a composition with sodium alginate loaded with a model antibacterial drug (imipinem). The characteristics of the prepared microparticles were studied using SEM, a particle size analyser (Zetasizer Nano ZS), and a spectrophotometer (Cary 60). Microparticles were obtained via solvent evaporation from triple emulsions. It has been established that the addition of sodium alginate affects the properties of microparticles: it increases the size and reduces the surface charge. It was shown that the efficiency of encapsulating imipinem into composite microparticles was almost three times higher compared to P3HB microparticles. In a model medium, prolonged release of the antibacterial drug was demonstrated over 28 days. The study of the biocompatability of microparticles in the culture of NIH 3T3 cells showed no negative effect. Using model Gram-positive and Gram-negative microorganisms as an example, it was shown that microparticles loaded with antibiotic showed antibacterial activity. Thus, it has been shown that the addition of sodium alginate has a positive effect on the properties of P3HB microparticles; namely, it allows increasing the efficiency of drug encapsulation, enhances the release of the drug from the microparticles, does not cause toxic reactions in cell culture, and also preserves the activity of the medicinal drug, which allows us to conclude that these composite microcarriers are promising for the development of long-acting dosage forms. This study was funded by the State Assignment of the Ministry of Science and Higher Education of the RF (project No. FWES-2021-0025).

Introduction: During minimally invasive surgery, laparoscopic lenses often get contaminated by fog and smoke, reducing video quality and affecting surgeon visibility. Various solutions have been proposed to detect and eliminate contamination in real time without interrupting the procedure.

Materials and Methods: This study utilizes the ResNet 18 architecture, modifying the output layer to contain five units corresponding to the classes in the Laparoscopic Video Quality (LVQ) database: noise (NO), smoke (SM), uneven illumination (UI), defocus blur (DB), and motion blur (MB). A review of existing patents revealed two significant systems for automatically detecting laparoscopic lens contamination. The first patent, by Ding et al., involves a system that activates a cleaning mechanism when image clarity falls below a threshold using pressurized liquid, air, and suction. However, it lacks details on the detection threshold and specific features used. The second patent, by Coffeen et al., describes a fluid-based cleaning system activated upon detecting lens deposits, but it does not specify the detection criteria. Both patents have limitations in the cleaning process. Inspired by Coffeen et al.'s patent, we propose an improved in vitro laparoscopic lens-cleaning device. Our device integrates a ResNet18-based detection system, automatically triggers cleaning, and optimizes fluid flow with angled nozzles. It uses warm saline and carbon dioxide, is safe for the human body, and fits through a standard-size trocar.

Results: Our detection system showed high performance, with 99.50% accuracy in training and 99.15% in validation. Performance metrics on 20 distorted LVQ videos revealed 100% accuracy for smoke and motion blur, 90% for noise and defocus blur, and 65% for uneven illumination.

Conclusion: The model demonstrates robust accuracy, particularly in detecting smoke, motion, and defocus blur, facilitating automated cleaning without surgeon intervention. Future research will test the lens-cleaning device prototype in real-world conditions and compare it with other cleaning devices.

Protein-based biomaterials are invisible to most medical imaging modalities, owing to their physical similarity to native tissue. This hinders the non-invasive monitoring of correct placement, longitudinal retention, and material integrity or degradation over time. As an exemplar of this problem, hernia mesh implantation is the most widely performed surgical operation at >20 million/year globally, with a complication rate >10%, where poor mesh detectability affects clinical management.

As a potential solution, click chemistry offers a versatile route towards minimally modified proteins, facilitating both the incorporation of contrast agents for multi-modality imaging and functionalisation with bioactive molecules for enhanced therapy. However, most amino-acid-specific coupling reactions have been thus far limited to the modification of small soluble proteins, owing to challenges such as the aqueous stability of reactive groups, and limited diffusivity into macromolecular materials.

Here, we present, for the first time, a tyrosine-specific diazonium coupling approach for labelling pre-formed protein scaffolds, including a clinically approved hernia mesh based on decellularised dermis (Bard, Xenmatrix). Using 2-Methoxy-4-nitrobenzene-1-diazonium 5-sulfonaphthalene-1-sulfonate we demonstrate the efficient labelling of a collagen-based hernia mesh, thereby enhancing optical properties to facilitate image-guided surgery. Reaction conditions were optimised to give even labelling throughout the scaffold volume, which we confirmed on 10 µm sections and microscopy. The retention of material properties post labelling was confirmed using mechanical testing, alongside cell-growth assays for biocompatibility. Non-invasive in vivo detection after subcutaneous implantation in mice was shown using photo-acoustic imaging at 680nm, revealing the longitudinal placement of materials at high resolution up to 2 months post implantation. Histology, including H+E, was performed to confirm unaltered inflammatory response.

This is the first time diazonium coupling has been used for the uniform modification of whole pre-formed protein scaffolds, expanding its use beyond small soluble proteins. We used this to produce a photo-acoustic visible hernia mesh, enabling non-invasive in vivo imaging over a biologically relevant timeframe.

Introduction: The design and production of patient-specific medical implants with high biocompatibility and good regeneration features is a still challenging task. Selective laser melting (SLM) is one of the most promising methods for manufacturing products with complex shapes and structures. The work is aimed at the development of physical and technological foundations for obtaining a proper mesh structure by SLM.

Methods: Numerical simulation was performed using COMSOL software to reveal the dependencies between the temperature gradient and SLM's technological parameters. A COXEM EM-30AXPlus scanning electron microscope was utilized for powder elemental analysis and microtopography. An SLM-50 realizer was adopted to produce the samples using SLM technology.

Results and Discussion: The primary technical, chemical, and physical attributes of the CoCr, TiNi, and Ti6Al4V powders were ascertained. Regimes for the temperature field distribution in the fusion zone were developed, and the penetration depth was determined. The dependencies between the technological parameters of SLM and the geometric characteristics of the CoCr, TiNi, and Ti6Al4V thin-walled structures were established. Functional Ti6Al4V cellular structures with cell sizes of 2-3 mm and a bridge thickness of 200 to 300 μm were manufactured to replace bone tissue defects. TiNi and CoCr coronary stents with a diameter of 2 to 6 mm and a strut size of 150 μm to 500 μm were produced.

Conclusions: TheSLM regimes developed provide minimal deviations in wall thickness from the 3D model and the proper penetration depth for designing defect-free thin-walled mesh structures.

The study was funded by a grant ffrom the Russian Science Foundation, No. 23-79-01284: https://rscf.ru/project/23-79-01284/.

Introduction: An application of the two-way fluid–structure interaction (2-way FSI) of an additively built CoCr stent design is presented in this paper. The objective of the work is to assess the stent's performance from a mechanical and hemodynamic point of view. Stress and strain distribution and wall shear stress (WSS), oscillatory shear index, and time-averaged WSS were analyzed.

Methods: Two-way FSI was used to model the biomechanical behaviour of three CoCr stent designs. The stent is exposed to pulsatile blood flow and is intended for use in cardiovascular applications. A finite element analysis (FEA) model for the stent structure is coupled with a computational fluid dynamics (CFD) model for blood flow as part of the FSI analysis. In this study, hyperelastic mechanical properties were used to describe the artery and plaque. A short artery model was taken into account.

Results and Discussion: The SIMPLE stent model is the most susceptible to restenosis. It was shown that the stress–strain state depends on a proper choice of boundary conditions. The maximum stresses occurred at 0.1 s and were concentrated at the ends of the artery. The minimum stresses were observed in the middle of the artery. The analysis showed that the plaque exhibited the maximum stresses of 0.2 MPa; these stresses were concentrated at the plaque edges. The stress-state analysis showed that maximum stresses reached 1.82 MPa. These stresses were also concentrated at the ends of the stent and in the bending region.

Conclusions: It was shown that stent design has an effect on the biomechanical performance of the stent in the artery. In particular, stent design has a significant impact on re-stenosis occurrence and development.

The study was funded by a grant of the Russian Science Foundation No. 23-79-01284, https://rscf.ru/project/23-79-01284/.