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Collagen membranes with high robustness and a defined stable biodegradation are of a great interest for dental surgery. Electrophoretic deposition (EPD) is a perspective candidate technology for their production, and in this article, the authors demonstrated the capabilities of its modification, a semipermeable barrier-assisted EPD (SBA-EPD). The SBA-EPD process was carried out at 60 V for 1,2, or 3 cycles 20 min each, after which the obtained membranes were crosslinked with 0.625% genipin. SBA-EPD allowed for the fabrication of membranes with high collagen packing density (0.0012 g/mm3) and high robustness, which depended on the number of SBA-EPD cycles. The highest Young's modulus, tensile strength, and strain at failure values of non-crosslinked samples corresponded to 3-cycle deposition (15.11 ± 1.78 MPa, 4.2 ± 1.6 MPa, 60 ± 12%, respectively). However, crosslinking diminished the statistical difference of these parameters among membranes of different deposition cycles (reaching for 3-cycle deposition 64 ± 5 MPa, 9.5 ± 1.1 MPa, 23.7 ± 2.0%, respectively). On day 21 after subcutaneous implantation, the non-crosslinked membranes showed a significant degree of resorption higher than that of crosslinked ones by 3.5 times in absolute values. As well, crosslinked membranes elicited a greater peri-implant pro-fibrotic and giant cell response. Overall, the mechanical characteristics of SBA-EPD membranes were mostly superior to commercially available products used for dental applications, while their biodegradation timeframes fitted the optimal window. The authors hope that their research will attract the attention to SBA-EPD as an emerging and perspective technology for the production of robust and defect-free collagen membranes for dental surgery. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are produced by various cells and exist in most biological fluids. They play an important role in cell–cell signaling, immune response, and tumor metastasis, and also have theranostic potential. They deliver many functional biomolecules, including DNA, microRNAs (miRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA), lipids, and proteins, thus affecting different physiological processes in target cells. Decreased immunogenicity compared to liposomes or viral vectors and the ability to cross through physiological barriers such as the blood–brain barrier make them an attractive and innovative option as diagnostic biomarkers and therapeutic carriers. Here, we highlighted two types of cells that can produce functional EVs, namely, mesenchymal stem/stromal cells (MSCs) and regulatory T cells (Tregs), discussing MSC/Treg-derived EV-based therapies for some specific diseases including acute respiratory distress syndrome (ARDS), autoimmune diseases, and cancer. [ABSTRACT FROM AUTHOR]

Liver cancer is the sixth common cancer and forth cause of cancer-related death worldwide. Based on usually advanced stages of hepatocellular carcinoma (HCC) at the time of diagnosis, therapeutic options are limited and, in many cases, not effective, and typically result in the tumor recurrence with a poor prognosis. Radioimmunotherapy (RIT) offers a selective internal radiation therapy approach using beta or alpha emitting radionuclides conjugated with tumor-specific monoclonal antibodies (mAbs), or specific selective peptides. When compared to chemotherapy or radiotherapy, radiolabeled mAbs against cancer-associated antigens could provide a high therapeutic and exclusive radiation dose for cancerous cells while decreasing the exposure-induced side effects to healthy tissues. The recent advances in cancer immunotherapy, such as blockade of immune-checkpoint inhibitors (ICIs), has changed the landscape of cancer therapy, and the efficacy of different classes of immunotherapy has been tested in many clinical trials. Taking into account the use of ICIs in the liver tumor microenvironment, combined therapies with different approaches may enhance the outcome in the future clinical studies. With the development of novel immunotherapy treatment options in the recent years, there has been a great deal of information about combining the diverse treatment modalities to boost the effectiveness of immunomodulatory drugs. In this opinion review, we will discuss the recent advancements in RIT. The current status of immunotherapy and internal radiotherapy will be updated, and we will propose novel approaches for the combination of both techniques. Potential target antigens for radioimmunotherapy in Hepatocellular carcinoma (HCC). HCC radioimmunotherapy target antigens are the most specific and commonly accessible antigens on the surface of HCC cells. CTLA-4 ligand and receptor, TAMs, PD-1/PD-L, TIM-3, specific IEXs/TEXs, ROBO1, and cluster of differentiation antigens CD105, CD147 could all be used in HCC radioimmunotherapy. Abbreviations: TAMs, tumor-associated macrophages; CTLA-4, cytotoxic T-lymphocyte associated antigen-4; PD-1, Programmed cell death protein 1; PD-L, programmed death-ligand1; TIM-3, T-cell immunoglobulin (Ig) and mucin-domain containing protein-3; IEXs, immune cell-derived exosomes; TEXs, tumor-derived exosomes. [ABSTRACT FROM AUTHOR]

The aim, as proof of concept, was to optimize niosomal formulations of tamoxifen in terms of size, morphology, encapsulation efficiency, and release kinetics for further treatment of the breast cancer (BC). Different assays were carried out to evaluate the pro-apoptotic and cytotoxicity impact of tamoxifen-loaded niosomes in two BC cells, MDA-MB-231 and SKBR3. In this study, tamoxifen was loaded in niosomes after optimization in the formulation. The formulation of niosomes supported maximized drug entrapment and minimized their size. The novel formulation showed improvement in storage stability, and after 60 days only, small changes in size, polydispersity index, and drug entrapment were observed. Besides, a pH-dependent release pattern of formulated niosomes displayed slow release at physiological pH (7.4) and a considerable increase of release at acidic pH (5.4), making them a promising candidate for drug delivery in the BC treatment. The cytotoxicity study exhibited high biocompatibility with MCF10A healthy cells, while remarkable inhibitory effects were observed after treatment of cancerous lines, MDA-MB-231, and SKBR3 cells. The IC50 values for the tamoxifen-loaded niosomes were significantly less than other groups. Moreover, treatment with drug-loaded niosomes significantly changed the gene expression pattern of BC cells. Statistically significant down-regulation of cyclin D, cyclin E, VEGFR-1, MMP-2, and MMP-9 genes and up-regulation of caspase-3 and caspase-9 were observed. These results were in correlation with cell cycle arrest, lessoned migration capacity, and increased caspase activity and apoptosis induction in cancerous cells. Optimization in the formulation of tamoxifen-loaded niosomes can make them a novel candidate for drug delivery in BC treatment. [ABSTRACT FROM AUTHOR]

Although the exact mechanism of pathogenesis in COVID-19 is not fully understood, cytokine storm following viral infection plays an important role in the initiation and progression of disease. They included mesenchymal stromal cell (MSC) therapies and adoptive T cell and natural killer (NK) cell therapies. Since regulatory T cells (Treg) are known as major anti-inflammatory T cell subsets, Treg cell therapy may be a novel regenerative and anti-inflammatory treatment strategy for COVID-19. Monoclonal antibodies in COVID-19 treatment It has been shown that monoclonal antibodies could be a promising treatment approach for COVID-19. [Extracted from the article]

Biological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates—spheroids—have become widely used model objects in the study of this phenomenon. Existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. This discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation. [ABSTRACT FROM AUTHOR]

Fibrin is one of the promising biomaterials in tissue engineering for creating favorable conditions for the formation of a capillary-like vascular network. The use of native fibrin is limited due to its rapid degradation and opacity. To improve its properties, including biological ones, various modifications have been proposed, for example, using functionalized polyethylene glycol (PEG). In this work, homobifunctional (O,O''-bis[2-(N-succinimidyl-succinylamino)ethyl])polyethylene glycol of various molecular weights was used to modify fibrin. The modification of fibrin with vascular endothelial growth factor was also analyzed for possible stimulation of the formation of tubule-like structures. Small-angle X-ray scattering (SAXS) data and ab initio modeling of the three-dimensional particle shape showed that PEG--fibrin conjugates consist of filamentous particles, depending on the size of the PEG molecule, the molar ratio of fibrin to PEG, and the presence or absence of vascular endothelial growth factor. [ABSTRACT FROM AUTHOR]

To date, there is no licensed treatment or approved vaccine to combat the coronavirus disease of 2019 (COVID-19), and the number of new cases and mortality multiplies every day. Therefore, it is essential to develop an effective treatment strategy to control the virus spread and prevent the disease. Here, we summarized the therapeutic approaches that are used to treat this infection. Although it seems that antiviral drugs are effective in improving clinical manifestation, there is no definite treatment protocol. Lymphocytopenia, excessive inflammation, and cytokine storm followed by acute respiratory distress syndrome are still unsolved issues causing the severity of this disease. Therefore, immune response modulation and inflammation management can be considered as an essential step. There is no doubt that more studies are required to clarify immunopathogenesis and immune response; however, new therapeutic approaches including mesenchymal stromal cell and immune cell therapy showed inspiring results. [ABSTRACT FROM AUTHOR]

We examined the accumulation of phenylethanol, geraniol, citronellol, and nerol by Eremothecium ashbyi Guillermond 1935 strains characterized by different levels of riboflavin synthesis. There was a significant positive correlation between riboflavin and monoterpene alcohol biosyntheses (Spearman's correlation coefficients = 0.81-1.00, p ≤ 0.05). Strain accumulation of the main secondary metabolites such as vitamin B and aroma forming compounds was found to be accompanied with an increase in the lipid droplet quantities and the vacuole filling with lipophilic compounds. These phenomena may be used as an indirect measure of riboflavinogenesis intensity and essential oil synthesis. [ABSTRACT FROM AUTHOR]

The engineering of blood vessels that could ensure efficient transport of various nutrients and metabolites is a challenge in tissue engineering. The creation of cell-seeded bioconstructs using modified natural polymers, in particular, PEGylated fibrin is under investigation, which will help overcome this problem. Therefore, the purpose of this study was to determine the optimal ratio of the hydrogel components of modified fibrin to provide favorable conditions for the vascular development of endothelial and mesenchymal stem cell coculture. We have shown that PEGylated fibrin gels are capable of maintaining three-dimensional growth of HUVEC and hASC cells. Hydrogel with a filamentous microporous structure obtained from PEGylated 5: 1 fibrinogen and thrombin at a concentration of 0.2 U per 1 mg ensured optimal conditions for spreading, growth, and development of cocultured cells as well as the expression of proteins involved in angiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: A 3D model of the shape of bovine fibrinogen, one of the proteins responsible for blood coagulation, is constructed based on small-angle X-ray scattering (SAXS) data on bovine fibrinogen in solution, and the oligomeric composition of fibrinogen in solution is estimated. It is shown that fibrinogen molecules form elongated vermicular structures with a length on the order of 50 nm and an effective cross section of about 10 nm. The volume of these particles correlates well with the volume of two fibrinogen dimers. The results obtained may be helpful when applying fibrinogen and its modifications in tissue engineering. [ABSTRACT FROM AUTHOR]