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Cerium oxide nanoparticles (CeONPs), as part of tissue regeneration matrices, can protect cells from reactive oxygen species and oxidative stress. In addition, they can influence the properties of the scaffold, including its electrospinnability and mechanical strength. In this work, we prepared electrospun fiber mats from a chitosan and polyethylene oxide blend (CS-PEO) with the addition of ceria nanoparticles (CS-PEO-CeONP). The addition of CeONPs resulted in a smaller fiber diameter and higher swelling compared to CS-PEO fiber mats. CeONP-modified fiber mats also had a higher Young’s modulus due to the reinforcing effect of the nanoparticles. Both mats had comparable adhesion and cytocompatibility to mesenchymal stem cells, which had a more rounded morphology on CS-PEO-CeONP compared to elongated cells on the CS-PEO mats. Biocompatibility in an in vivo rat model showed no acute toxicity, no septic or allergic inflammation, and no rough scar tissue formation. The degradation of both mats passed the stage of matrix swelling. CS-PEO-CeONP showed significantly slower biodegradation, with most of the matrix remaining in the tissue after 90 days. The reactive inflammation was aseptic in nature with the involvement of multinucleated foreign-body type giant cells and was significantly reduced by day 90. CeONPs induced the formation of the implant’s connective tissue capsule. Thus, the introduction of CeONPs influenced the physicochemical properties and biological activity of CS-PEO nanofiber mats.

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

In this work, new composite films were prepared by incorporating the disintegrated bacterial cellulose (BCd) nanofibers and cerium oxide nanoparticles into chitosan (CS) matrices. The influence of the amount of nanofillers on the structure and properties of the polymer composites and the specific features of the intermolecular interactions in the materials were determined. An increase in film stiffness was observed as a result of reinforcing the CS matrix with BCd nanofibers: the Young’s modulus increased from 4.55 to 6.3 GPa with the introduction of 5% BCd. A further increase in Young’s modulus of 6.7 GPa and a significant increase in film strength (22% increase in yield stress compared to the CS film) were observed when the BCd concentration was increased to 20%. The amount of nanosized ceria affected the structure of the composite, followed by a change in the hydrophilic properties and texture of the composite films. Increasing the amount of nanoceria to 8% significantly improved the biocompatibility of the films and their adhesion to the culture of mesenchymal stem cells. The obtained nanocomposite films combine a number of favorable properties (good mechanical strength in dry and swollen states, improved biocompatibility in relation to the culture of mesenchymal stem cells), which allows us to recommend them for use as a matrix material for the culture of mesenchymal stem cells and wound dressings.

Elaboration of protocols for differentiation of human pluripotent stem cells to dopamine neurons is an important issue for development of cell replacement therapy for Parkinson’s disease. A number of protocols have been already developed; however, their efficiency and specificity still can be improved. Investigating the role of signaling cascades, important for neurogenesis, can help to solve this problem and to provide a deeper understanding of their role in neuronal development. Notch signaling plays an essential role in development and maintenance of the central nervous system after birth. In our study, we analyzed the effect of Notch activation and inhibition at the early stages of differentiation of human induced pluripotent stem cells to dopaminergic neurons. We found that, during the first seven days of differentiation, the cells were not sensitive to the Notch inhibition. On the contrary, activation of Notch signaling during the same time period led to significant changes and was associated with an increase in expression of genes, specific for caudal parts of the brain, a decrease of expression of genes, specific for forebrain, as well as a decrease of expression of genes, important for the formation of axons and dendrites and microtubule stabilizing proteins.

A new biocompatible nanocomposite film material for cell engineering and other biomedical applications has been prepared. It is based on the composition of natural polysaccharides filled with cerium oxide nanoparticles (CeONPs). The preparative procedure consists of successive impregnations of pressed bacterial cellulose (BC) with a sodium alginate (ALG) solution containing nanoparticles of citrate-stabilized cerium oxide and a chitosan (CS) solution. The presence of CeONPs in the polysaccharide composite matrix and the interaction of the nanoparticles with the polymer, confirmed by IR spectroscopy, change the network architecture of the composite. This leads to noticeable changes in a number of properties of the material in comparison with those of the matrix’s polysaccharide composition, viz., an increase in mechanical stiffness, a decrease in the degree of planar orientation of BC macrochains, an increase in hydrophilicity, and the shift of the processes of thermo-oxidative destruction of the material to a low-temperature region. The latter effect is considered to be caused by the redox activity of cerium oxide (reversible transitions between the states Ce4+ and Ce3+) in thermally stimulated processes in the nanocomposite films. In the equilibrium swollen state, the material retains a mechanical strength at the level of ~2 MPa. The results of in vitro tests (cultivation of multipotent mesenchymal stem cells) have demonstrated the good biocompatibility of the BC-ALG(CeONP)-CS film as cell proliferation scaffolds.

Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients. Among them, 129 patients were then randomized into two groups with similar concomitant medication. Group I (n = 56) received a bolus of cholecalciferol at a dose of 50,000 IU on the first and the eighth days of hospitalization. Patients from Group II (n = 54) did not receive the supplementation. We found significant differences between groups with the preferential increase in serum 25(OH)D level and Δ 25(OH)D in Group I on the ninth day of hospitalization (p < 0.001). The serum 25(OH)D level on the ninth day was negatively associated with the number of bed days (r = −0.23, p = 0.006); we did not observe other clinical benefits in patients receiving an oral bolus of cholecalciferol. Moreover, in Group I, neutrophil and lymphocyte counts were significantly higher (p = 0.04; p = 0.02), while the C-reactive protein level was significantly lower on the ninth day of hospitalization (p = 0.02). Patients with supplementation of 100,000 IU of cholecalciferol, compared to those without supplementation, showed a decrease in the frequencies of CD38++CD27 transitional and CD27−CD38+ mature naive B cells (p = 0.006 and p = 0.02) and an increase in the level of CD27−CD38− DN B cells (p = 0.02). Thus, the rise in serum 25(OH)D level caused by vitamin D supplementation in vitamin D insufficient and deficient patients may positively affect immune status and hence the course of COVID-19.

Polysaccharide-based cryogels are promising materials for producing scaffolds in tissue engineering. In this work, we obtained ultralight (0.046–0.162 g/cm3) and highly porous (88.2–96.7%) cryogels with a complex hierarchical morphology by dissolving cellulose in phosphoric acid, with subsequent regeneration and freeze-drying. The effect of the cellulose dissolution temperature on phosphoric acid and the effect of the freezing time of cellulose hydrogels on the structure and properties of the obtained cryogels were studied. It has been shown that prolonged freezing leads to the formation of denser and stronger cryogels with a network structure. The incorporation of chitin nanowhiskers led to a threefold increase in the strength of the cellulose cryogels. The X-ray diffraction method showed that the regenerated cellulose was mostly amorphous, with a crystallinity of 26.8–28.4% in the structure of cellulose II. Cellulose cryogels with chitin nanowhiskers demonstrated better biocompatibility with mesenchymal stem cells compared to the normal cellulose cryogels.

A low 25-hydroxyvitamin D (25(OH)D) level is considered as an independent risk factor for COVID-19 severity. However, the association between vitamin D status and outcomes in COVID-19 is controversial. In the present study we investigate the association between the serum 25(OH)D level, immune response, and clinical disease course in patients with COVID-19. A total of 311 patients hospitalized with COVID-19 were enrolled. For patients with a vitamin D deficiency/insufficiency, the prevalence of severe COVID-19 was higher than in those with a normal 25(OH)D level (p < 0.001). The threshold of 25(OH)D level associated with mortality was 11.4 ng/mL (p = 0.003, ROC analysis). The frequency of CD3+CD4+ T helper (Th) cells was decreased in patients with 25(OH)D level ≤ 11.4 ng/mL, compared to healthy controls (HCs). There were no differences in the frequency of naive, central memory (CM), effector memory (EM), and terminally differentiated effector memory Th cells in patients with COVID-19 compared to HCs. The frequency of T-follicular helpers was decreased both in patients with 25(OH)D level > 11.4 ng/mL (p < 0.001) and 25(OH)D level ≤ 11.4 ng/mL (p = 0.003) compared to HCs. Patients with 25(OH)D level > 11.4 ng/mL had an increased frequency of Th2 CM (p = 0.010) and decreased Th17 CM (p < 0.001). While the frequency of Th2 EM was significantly increased, the frequency of Th17 EM was significantly decreased in both groups compared to HCs. Thus, 25(OH)D level is an independent risk factor for the disease severity and mortality in patients with COVID-19. We demonstrate that the serum 25(OH)D level ≤ 11.4 ng/mL is associated with the stimulation of Th2 and the downregulation of Th17 cell polarization of the adaptive immunity in patients with COVID-19.

The development of intravitreal glucocorticoid delivery systems is a current global challenge for the treatment of inflammatory diseases of the posterior segment of the eye. The main advantages of these systems are that they can overcome anatomical and physiological ophthalmic barriers and increase local bioavailability while prolonging and controlling drug release over several months to improve the safety and effectiveness of glucocorticoid therapy. One approach to the development of optimal delivery systems for intravitreal injections is the conjugation of low-molecular-weight drugs with natural polymers to prevent their rapid elimination and provide targeted and controlled release. This study focuses on the development of a procedure for a two-step synthesis of dexamethasone (DEX) conjugates based on the natural polysaccharide chitosan (CS). We first used carbodiimide chemistry to conjugate DEX to CS via a succinyl linker, and we then modified the obtained systems with succinic anhydride to impart a negative ζ-potential to the polymer particle surface. The resulting polysaccharide carriers had a degree of substitution with DEX moieties of 2–4%, a DEX content of 50–85 μg/mg, and a degree of succinylation of 64–68%. The size of the obtained particles was 400–1100 nm, and the ζ-potential was −30 to −33 mV. In vitro release studies at pH 7.4 showed slow hydrolysis of the amide and ester bonds in the synthesized systems, with a total release of 8–10% for both DEX and succinyl dexamethasone (SucDEX) after 1 month. The developed conjugates showed a significant anti-inflammatory effect in TNFα-induced and LPS-induced inflammation models, suppressing CD54 expression in THP-1 cells by 2- and 4-fold, respectively. Thus, these novel succinyl chitosan-dexamethasone (SucCS-DEX) conjugates are promising ophthalmic carriers for intravitreal delivery.

A series of novel polysaccharide-based biocomposites was obtained by impregnation of bacterial cellulose produced by Komagataeibacter rhaeticus (BC) with the solutions of negatively charged polysaccharides—hyaluronan (HA), sodium alginate (ALG), or κ-carrageenan (CAR)—and subsequently with positively charged chitosan (CS). The penetration of the polysaccharide solutions into the BC network and their interaction to form a polyelectrolyte complex changed the architecture of the BC network. The structure, morphology, and properties of the biocomposites depended on the type of impregnated anionic polysaccharides, and those polysaccharides in turn determined the nature of the interaction with CS. The porosity and swelling of the composites increased in the order: BC–ALG–CS > BC–HA–CS > BC–CAR–CS. The composites show higher biocompatibility with mesenchymal stem cells than the original BC sample, with the BC–ALG–CS composite showing the best characteristics.

In this work, a bilayer chitosan/sodium alginate scaffold was prepared via a needleless electrospinning technique. The layer of sodium alginate was electrospun over the layer of chitosan. The introduction of partially deacetylated chitin nanowhiskers (CNW) stabilized the electrospinning and increased the spinnability of the sodium alginate solution. A CNW concentration of 7.5% provided optimal solution viscosity and structurization due to electrostatic interactions and the formation of a polyelectrolyte complex. This allowed electrospinning of defectless alginate nanofibers with an average diameter of 200–300 nm. The overall porosity of the bilayer scaffold was slightly lower than that of a chitosan monolayer, while the average pore size of up to 2 μm was larger for the bilayer scaffold. This high porosity promoted mesenchymal stem cell proliferation. The cells formed spherical colonies on the chitosan nanofibers, but formed flatter colonies and monolayers on alginate nanofibers. The fabricated chitosan/sodium alginate bilayer material was deemed promising for tissue engineering applications.

A bilayer nonwoven material for tissue regeneration was prepared from chitosan (CS) and hyaluronic acid (HA) by needleless electrospinning wherein 10−15 wt% (with respect to polysaccharide) polyethylene oxide was added as spinning starter. A fiber morphology study confirmed the material’s uniform defect-free structure. The roughness of the bilayer material was in the range of 1.5−3 μm, which is favorable for cell growth. Electrospinning resulted in the higher orientation of the polymer structure compared with that of corresponding films, and this finding may be related to the orientation of the polymer chains during the spinning process. These structural changes increased the intermolecular interactions. Thus, despite a high swelling degree of 1.4−2.8 g/g, the bilayer matrix maintained its shape due to the large quantity of polyelectrolyte contacts between the chains of oppositely charged polymers. The porosity of the bilayer CS−HA nonwoven material was twice lower, while the Young’s modulus and break stress were twice higher than that of a CS monolayer scaffold. Therefore, during the electrospinning of the second layer, HA may have penetrated into the pores of the CS layer, thereby increasing the polyelectrolyte contacts between the two polymers. The bilayer CS−HA scaffold exhibited good compatibility with mesenchymal stem cells. This characteristic makes the developed material promising for tissue engineering applications.

In this study, thin calcium phosphate (Ca-P) coatings were deposited on zirconia substrates by radiofrequency (RF) magnetron sputtering using different calcium phosphate targets (calcium phosphate tribasic (CPT), hydroxyapatite (HA), calcium phosphate monobasic, calcium phosphate dibasic dehydrate (DCPD) and calcium pyrophosphate (CPP) powders). The sputtering of calcium phosphate monobasic and DCPD powders was carried out without an inert gas in the self-sustaining plasma mode. The physico-chemical, mechanical and biological properties of the coatings were investigated. Cell adhesion on the coatings was examined using mesenchymal stem cells (MSCs). The CPT coating exhibited the best cell adherence among all the samples, including the uncoated zirconia substrate. The cells were spread uniformly over the surfaces of all samples.