Katarina Virijević

Objective and design: To test whether the hypoxia-inducible factor 1-alpha (HIF1A) axis links transcriptional, cellular, biomarker and host-genetic features of severe COVID-19, in a retrospective multi-scale observational study of public cohorts and one hospital cohort. Material or subjects: 35,268 hospitalized patients (Mexican national registry); 1,100 samples from five bulk RNA-seq cohorts; 25,773 peripheral neutrophils from six individuals; 326 hospitalized patients (São Paulo, Brazil); 93 hospitalized patients (University Clinical Center Kragujevac, Serbia). Treatment: None. Methods: Within-cohort effect sizes for a 10-gene HIF1A panel; single-cell pathway scoring; logistic regression and gradient boosting with SHAP; TaqMan genotyping of HIF1A rs11549465 and rs41508050; cross-validation with bootstrap confidence intervals. Results: HIF1A (mean Cohen’s d +0.39) and LDHA (+0.76) were higher in severe disease in all five cohorts. Neutrophils of all three patients who failed extubation scored higher than those of both weaned patients and over-expressed S100A8/A9. C-reactive protein dominated ICU prediction; laboratory variables raised the AUC from 0.636 to 0.794. In Kragujevac, a clinical model predicted severe outcome (AUC 0.84, 95% CI 0.75–0.92). rs11549465 CT/TT carriers had lower mortality (1/11 vs 28/78; p = 0.095). Conclusions: HIF1A pathway activation is reproducible across cohorts and localizes to an alarmin-rich neutrophil state; host-genetic effects require larger cohorts.

Gelatin-based hydrogels are attractive bioinks for extrusion bioprinting because they combine biocompatibility, tunable rheology, and the ability to incorporate bioactive compounds. In this study, a novel multicomponent gelatin hydrogel containing fish oil, Tween 80, lecithin, glycerin, psyllium husk, and ascorbic acid was initially designed using AI-supported formulation screening and subsequently optimized experimentally for extrusion-based 3D printing. Nine acellular hydrogel constructs were fabricated using printing speeds of 1, 2, and 5 mm/s and infill densities of 5, 15, and 30%. Optical imaging, storage stability, experimentally measured density, water-contact-angle measurements, ATR-FTIR spectroscopy, and compression testing using flat cylindrical and spherical indenters were employed to characterize the printed constructs. Mass losses exceeded 60% after 7 days and reached approximately 91% after 110 days. Measured densities ranged from 0.22 to 1.24 g/cm³ across samples. All samples were hydrophilic, with contact angles of 30.07–50.63°, and higher infill increased contact angle. ATR-FTIR showed similar chemical profiles, with no clear infill-related chemical changes, suggesting that mechanical differences mainly reflected physical architecture and heterogeneity. Flat indentation generally produced higher maximum loads, except for sample S6, which reached 396.24 N under spherical loading and had the highest density (1.24 g/cm³), suggesting that its exceptional mechanical response may be associated with local material compactness and structural heterogeneity. Stress-ratio analysis yielded a mean σr/σtrue value of 4.43 with a coefficient of variation of 97.41%, while Bland–Altman analysis showed a mean bias of 0.15 MPa and limits of agreement from −0.70 to 1.01 MPa, demonstrating that the two testing methods are not directly interchangeable. Overall, hydrogel composition, internal network structure, printing infill, and local contact mechanics influenced mechanical behavior, highlighting the need for reproducible, method-specific hydrogel characterization.

Advanced biocompatible piezoelectric composites have gained significant attention for the development of flexible medical devices and especially related to materials structures that mimic the natural tissue structures. Natural piezoelectricity within the human tissues is reviewed, together with nature-based piezoelectric materials, their advantages and potential for designing the structures for biomedical applications. Electrospun Polyvinylidene fluoride (PVDF) nanofiber matrix, reinforced with silver nanoparticles (AgNPs) is discussed, including specific applications in bone grafts, biosensors and energy harvesting. Processing parameters of the electrospinning fabrication technology have a strong influence on the composite piezoelectricity. Computational models of piezoelectric composites have become a major support in material design for the real case applications. Existing approaches to the numerical modeling of piezoelectric composites have been shortly reviewed toward a recent trend of AI supported modeling for providing effective composite properties, prediction and optimization of material properties and behavior, such as the output voltage and power. Polymer-based biomedical piezoelectric composites have shown excellent results in laboratory research from aspects of their flexibility and possibility to tailor their electro-mechanical properties. However, output piezoelectric signals are still much lower than in the case of traditional ceramic-based materials, including challenges related to the stability of the electric signal, signal noise, piezoelectric impedance and durability of composites with nature-based reinforcements. Future directions in custom composite design, including currently available computational models to enable more rapid development of biomedical piezoelectrics are elaborated at the end.

This study focuses on preparing piezoelectric polyvinylidene fluoride (PVDF) nanocomposites reinforced with silver nanoparticles (AgNPs) using an electrospinning process. The aim of this study is to assess AgNPs’ influence on the piezoelectric properties of PVDF and, therefore, create an optimal piezoelectric composite with enhanced properties, enabling its application in various fields both as sensor and actuator. Because electrical stimuli have proven to have a positive influence in tissue engineering, combined with AgNPs, which have antimicrobial properties, these composites demonstrate a promising opportunity for application as biomedical scaffolds. The proposed scaffolds were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. In addition, mechanical properties are studied through tensile tests, while piezoelectric response is measured on an in-house built setup coupling mechanical stimuli and electrical response monitoring. An experimental test was combined with numerical simulations through the COMSOL Multiphysics version 6.3 software package, and this paper also presents a short review of the numerical and analytical methods used for the modelling and simulation of piezoelectric composites.

Uncontrolled, routine use of antibiotics has led to the development of antibiotic resistance in microorganisms, which is a clinical problem of global proportions. Many plants have been recognized as a resource of natural antimicrobial compounds that can potentially be effective in the treatment of bacterial infections. At the same time, technological progress has enabled the application of new materials in the field of medicine, such as micro and nanofibers. Therefore, the aim of this research is to examine the antimicrobial activity of nanofibers fabricated via electrospinning of solutions containing methanolic extract of Trapa natans L. and antibiotics. To determine the antimicrobial activity the microdilution method and the welland disk-diffusion method were used. The results indicated a promising potential in achieving antimicrobial activity, both for the plant and for the combination of nanofibers. The methanol extract of T. natans showed the highest activity against Bacillus subtilis ATTC 6633, by the microdilution method, while by the disk-diffusion method, the submerged variant of the nanofibers showed a zone of inhibition against Staphylococcus aureus ATCC 25923, which was better than the nanofibers and the antibiotic in two of the three analyzed concentrations.

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is a common heart disorder characterized by the thickening of the heart muscle, particularly in the left ventricle, which increases the risk of cardiac complications. This study aims to analyze the expression of apoptosis-regulating genes (CASP8, CASP9, CASP3, BAX, and BCL2) in blood samples from HCM patients, to better understand their potential as biomarkers for disease progression. Methods: Quantitative real-time PCR (qPCR) was used to evaluate gene expression in blood samples from 93 HCM patients. The correlation between apoptosis-regulating genes was conducted and clinical parameters were integrated for feature importance and clustering analysis. Results: Most patients exhibited significant downregulation of CASP8, CASP9, and CASP3. In contrast, BAX expression was elevated in 71 out of 93 patients, while BCL2 was increased in 55 out of 93 patients. Correlation analysis revealed weak negative correlations between the BAX/BCL2 ratio and CASP gene expression. Conclusions: These findings suggest that reduced expression of apoptotic genes may indicate a protective cellular mechanism, which could serve as a biomarker for disease progression. Further studies are needed to investigate the potential for therapeutic modulation of these pathways to improve patient outcomes.

This study focused on preparing composite nanomats by incorporating silver nanoparticles (AgNPs) in polyvinylidene fluoride (PVDF) nanofibers through the electrospinning process. A short review of piezoelectric PVDF-related research is presented. PVDF is known for its biocompatibility and piezoelectric properties. Since electrical signals in biological tissues have been shown to be relevant for therapeutic applications, the influence of the addition of AgNPs to PVDF on its piezoelectricity is studied, due to the ability of AgNPs to increase the piezoelectric signal, along with providing antibacterial properties. The prepared samples were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. In addition, the biological activity of composites was examined using a cytotoxicity assay and an assessment of the antibacterial activity. The obtained results show that the incorporation of AgNPs into PVDF nanofibers further enhances the piezoelectricity (crystalline β-phase fraction), already improved by the electrospinning process, compared to solution-casted samples, but only with a AgNPs/PVDF concentration of up to 0.3%; a further increase in the nanoparticles led to a β-phase reduction. The cytotoxicity assay showed a promising effect of PVDF/AgNPs nanofibers on the MDA-MB-231 breast cancer cell line, following the non-toxicity displayed in regard to the healthy MRC-5 cell line. The antibacterial effect of PVDF/AgNPs nanofibers showed promising antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus, as a result of the Ag content. The anticancer activity, combined with the electrical properties of nanofibers, presents new possibilities for smart, multifunctional materials for cancer treatment development.

Recent advances in regenerative medicine provide encouraging strategies to produce artificial skin substitutes. Gelatin scaffolds are successfully used as wound-dressing materials due to their superior properties, such as biocompatibility and the ability to mimic the extracellular matrix of the surrounding environment. In this study, five gelatin combination solutions were prepared and successfully electrospun using an electrospinning technique. After careful screening, the optimal concentration of the most promising combination was selected for further investigation. The obtained scaffolds were crosslinked with 25% glutaraldehyde vapor and characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy. The incorporation of antibiotic agents such as ciprofloxacin hydrochloride and gentamicin sulfate into gelatin membranes improved the already existing antibacterial properties of antibiotic-free gelatin scaffolds against Pseudomonas aeruginosa and Staphylococcus aureus. Also, the outcomes from the in vivo model study revealed that skin regeneration was significantly accelerated with gelatin/ciprofloxacin scaffold treatment. Moreover, the gelatin nanofibers were found to strongly promote the neoangiogenic process in the in vivo chick embryo chorioallantoic membrane assay. Finally, the combination of gelatin’s extracellular matrix and antibacterial agents in the scaffold suggests its potential for effective wound-healing treatments, emphasizing the importance of gelatin scaffolds in tissue engineering.

Here, an artificial intelligence (AI)-based approach was employed to optimize the production of electrospun scaffolds for in vivo wound healing applications. By combining polycaprolactone (PCL) and poly(ethylene glycol) (PEG) in various concentration ratios, dissolved in chloroform (CHCl₃) and dimethylformamide (DMF), 125 different polymer combinations were created. From these polymer combinations, electrospun nanofiber meshes were produced and characterized structurally and mechanically via microscopic techniques, including chemical composition and fiber diameter determination. Subsequently, these data were used to train a neural network, creating an AI model to predict the optimal scaffold production solution. Guided by the predictions and experimental outcomes of the AI model, the most promising scaffold for further in vitro analyses was identified. Moreover, we enriched this selected polymer combination by incorporating antibiotics, aiming to develop electrospun nanofiber scaffolds tailored for in vivo wound healing applications. Our study underscores three noteworthy conclusions: (i) the application of AI is pivotal in the fields of material and biomedical sciences, (ii) our methodology provides an effective blueprint for the initial screening of biomedical materials, and (iii) electrospun PCL/PEG antibiotic-bearing scaffolds exhibit outstanding results in promoting neoangiogenesis and facilitating in vivo wound treatment.