COVID-19, being a life-threatening infection that evolves rapidly, remains a major public health concern calling for the development of vaccines with broad protection against different pathogenic strains and high immunogenicity. Aside from this, other concerns in mass immunization settings are also the scalability of production and relative affordability of the technology. In that regard, adjuvanted protein vaccines with particles mimicking the virus stand out among known vaccine technologies. The “Betuvax-CoV-2” vaccine, developed on the basis of a recombinant protein and an adjuvant, has already been tested in preclinical studies and has advanced to clinical evaluation. Open, double-blinded, placebo-controlled, randomized phase I/II clinical trial of the “Betuvax-CoV-2,” recombinant protein subunit vaccine based on the S-protein RBD fused with the Fc-fragment of IgG, was conducted to evaluate safety and immunogenicity in response to the vaccination. Methods: In the phase I/II clinical trial, 116 healthy adult men and women, ages 18–58, were enrolled: 20 in Stage I, and 96 in Stage II. In Stage I, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 1) or 20 µg (group 2) on day 30. In Stage II, 20 µg of the vaccine was administered intramuscularly on day 2, and either 5 µg (group 3) or 20 µg (group 4) on day 30. In group 5, both injections were replaced with placebo. The primary outcome measures were safety (number of participants with adverse events throughout the study) and antigen-specific humoral immunity (SARS-CoV-2-specific antibodies measured by ELISA and CMIA). Antigen-specific cell-mediated immunity and changes in neutralizing antibodies (detected with a SARS-CoV-2 neutralization assay) were measured as a secondary outcome. The trial is registered with ClinicalTrials.gov (Study Identifier: NCT05270954). Findings: Both vaccine formulations (20 µg + 5 µg and 20 µg + 20 µg) were safe and well tolerated. Most adverse events were mild, and no serious adverse events were detected. On day 51,anti-SARS-CoV-2 total and IgG antibody titers and anti-SARS-CoV-2 neutralizing antibodies were significantly higher in the vaccine groups (both formulations) than in the placebo. A more pronounced CD4+-mediated immune response was observed in the group of volunteers administered with the 20 + 20 μg vaccine formulation. Interpretations: RBD-Fc-based COVID-19 “Betuvax-CoV-2” vaccine in doses (20 + 5 µg and 20 + 20 µg) demonstrated an excellent safety profile and induced a strong humoral response. Further research on the protective effectiveness of the “Betuvax-CoV-2” vaccine for the prevention of COVID-19 is on its way.
A technology to create a cell-seeded fibrin-based implant matching the size and shape of bone defect is required to create an anatomical implant. The aim of the study was to develop a technology of cell-seeded fibrin gel implant creation that has the same shape and size as the bone defect at the site of implantation. Using computed tomography (CT) images, molds representing bone defects were created by 3D printing. The form was filled with fibrin glue and human dental pulp stem cells (DPSC). The viability, set of surface markers and osteogenic differentiation of DPSC grown in fibrin gel along with the clot retraction time were evaluated. In mice, an alveolar bone defect was created. The defect was filled with fibrin gel seeded with mouse DPSC. After 28 days, the bone repair was analyzed with cone beam CT and by histological examination. The proliferation rate, set of surface antigens and osteogenic potential of cells grown inside the scaffold and in 2D conditions did not differ. In mice, both cell-free and mouse DPSC-seeded implants increased the bone tissue volume and vascularization. In mice with cell-seeded gel implants, the bone remodeling process was more prominent than in animals with a cell-free implant. The technology of 3D-printed forms for molding implants can be used to prepare implants using components that are not suitable for 3D printing.
The review addresses physico-chemical aspects of interaction between macro-, micro-and nano-structured units of matter with the analysis of interface and grain boundary entities (nonautonomous phases) mechanisms and formation, as well as methods of their control in order to achieve the desired functional properties of nanostructured materials. Construction of these materials involves identification of thermodynamic and kinetic regularities in the organization processes, state and genesis parameters of nonautonomous phases formed as specific nanosized structures in a limited space between the macroscopic volume phases and with the limited amount of substance, which differ significantly on their properties, structure and composition from the appropriate characteristics of volume phases. Studying them is based on the application and development of theoretical and experimental methods of non-equilibrium thermodynamics, chemical kinetics, nonlinear dynamics and fractal analysis to determine the conditions of self-organization or materials directed synthesis with a high content of nonautonomous phases.
This work examines a biomechanical system consisting of the hip endoprosthesis and bones of the pelvic region of a person under a load corresponding to the equilibrium of a person in double-supported state. An assessment of the strength of a customised endoprosthesis has been carried out based on the analysis of the stress-strain state of the finite element model of the "skeleton-hip prosthesis" system when tightening the screws and when the system is subjected the person's weight; dangerous areas of the pelvic bone with high level of stresses have been identified. As recommendations, optimization of the location and number of screws used in order to create a more uniform stress distribution is proposed.
Purposes are to determine1) what frequency and what degree is of custom acetabular implants malposition in comparison with planned position, 2) what the reason of malposition is and 3) what the malposition consequences we can wait for.Patients and methods. The observation group included 20 patients (18 women and 2 men) with severe ac-etabular defects. Mean age of patients made up 53 (22-72) years. Position of the implants was compared with the parameters of preoperative planning using 5 postoperative CT indices (inclination, anteversion of semi-spherical part of the implant, spatial location of the rotation center in three axes). More than 10° deviation for inclination or anteversion and 5° dislocation of the rotation center in any axis was considered as a malposition of the component.Results. Only 5 of 20 constructions matched conditionally permissible limits by all the parameters. Most often excessive dislocation of the rotation center in lateral direction (10 cases) and excessive anteversion (9 cases) were observed. During 6 weeks follow up no complications related to the acetabular component position were recorded.Conclusion. It was shown that at revision arthroplasty with custom-made implants the probability of implant malposition as compared to the preoperative plan. The main reason could be the complexity of intraoperative orientation under conditions of abnormal hip anatomy. Malposition of the implants beyond the stated values did not result in complications within the early postoperative period. The longer follow up is required for the assessment of the long-term results.
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