Peripheral Blood Mononuclear Cell-Related Biomarkers in Schizophrenia.

INTRODUCTION: Schizophrenia is a severe mental illness causing significant impairment in personal, family, social, educational, occupational, and other important areas of life. While there is no widely accepted endophenotype, peripheral blood cells may serve as an accessible model of intracellular changes in schizophrenia. METHODS: We reviewed the literature on the query "peripheral blood mononuclear cells AND schizophrenia" in Medline (Pubmed), selecting studies that searched for specific biomarkers of schizophrenia. We considered both diagnostic biomarkers and biomarkers of therapeutic response, specific schizophrenia disorders or differential diagnostic biomarkers. RESULTS: We retrieved 41 articles matching the search criteria, among which were studies that considered changes in the production of pro-inflammatory and anti-inflammatory markers, proteins, receptors, enzyme activity, and gene expression as potential biomarkers. CONCLUSION: Approaches analysing a biological axis or a group of related biomarkers may hold the greatest promise for identifying schizophrenia. In addition, pharmacological status, smoking status, inflammatory markers and glucose metabolites, the presence of comorbidities should be considered. Certain biomarkers, while not specific for the diagnosis of schizophrenia, may indicate the prognosis and effectiveness of treatment in the established diagnosis.

Mass Spectrometry of Collagen-Containing Allogeneic Human Bone Tissue Material.

The current paper highlights the active development of tissue engineering in the field of the biofabrication of living tissue analogues through 3D-bioprinting technology. The implementation of the latter is impossible without important products such as bioinks and their basic components, namely, hydrogels. In this regard, tissue engineers are searching for biomaterials to produce hydrogels with specified properties both in terms of their physical, mechanical and chemical properties and in terms of local biological effects following implantation into an organism. One of such effects is the provision of the optimal conditions for physiological reparative regeneration by the structural components that form the basis of the biomaterial. Therefore, qualitative assessment of the composition of the protein component of a biomaterial is a significant task in tissue engineering and bioprinting. It is important for predicting the behaviour of printed constructs in terms of their gradual resorption followed by tissue regeneration due to the formation of a new extracellular matrix. One of the most promising natural biomaterials with significant potential in the production of hydrogels and the bioinks based on them is the polymer collagen of allogeneic origin, which plays an important role in maintaining the structural and biological integrity of the extracellular matrix, as well as in the morphogenesis and cellular metabolism of tissues, giving them the required mechanical and biochemical properties. In tissue engineering, collagen is widely used as a basic biomaterial because of its availability, biocompatibility and facile combination with other materials. This manuscript presents the main results of a mass spectrometry analysis (proteomic assay) of the lyophilized hydrogel produced from the registered Lyoplast® bioimplant (allogeneic human bone tissue), which is promising in the field of biotechnology. Proteomic assays of the investigated lyophilized hydrogel sample showed the presence of structural proteins (six major collagen fibers of types I, II, IV, IX, XXVII, XXVIII were identified), extracellular matrix proteins, and mRNA-stabilizing proteins, which participate in the regulation of transcription, as well as inducer proteins that mediate the activation of regeneration, including the level of circadian rhythm. The research results offer a new perspective and indicate the significant potential of the lyophilized hydrogels as an effective alternative to synthetic and xenogeneic materials in regenerative medicine, particularly in the field of biotechnology, acting as a matrix and cell-containing component of bioinks for 3D bioprinting.

Information-Thermodynamic Method for the Study of Proliferation of Organized Cellular Structure.

The aim of the article was to develop an innovative method for the study of cell proliferation based on the information-thermodynamic approach, including the mathematical ratio-the entropy of cell proliferation and an algorithm for the calculation of fractal dimension of the cellular structure. Approbation of this method with pulsed electromagnetic impact on culture in vitro was implemented. It is shown on the basis of experimental data that the organized cellular structure of juvenile human fibroblasts is a fractal. The method makes it possible to determine the stability of the effect on cell proliferation. The prospects for the application of the developed method are discussed.

Amniotic Membrane Biopolymer for Regenerative Medicine.

Biopolymers based on the amniotic membrane compare favorably with synthetic materials in that, along with a specific 2D structure, they have biologically active properties. However, in recent years, there has been a tendency to perform decellularization of the biomaterial during the preparation of the scaffold. In this study, we studied the microstructure of 157 samples and identified individual biological components in the manufacture of a medical biopolymer from an amniotic membrane using various methods. Group 1 had 55 samples, and the amniotic membrane was impregnated with glycerol and dried over silica gel. Group 2 had 48 samples, and the decellularized amniotic membrane was impregnated with glycerol followed by lyophilization, Group 3 had 44 samples, and the decellularized amniotic membrane without pre-impregnation with glycerol was subjected to lyophilization. Decellularization was performed by treatment with a low-frequency ultrasound at a frequency of 24-40 kHz in an ultrasonic bath. A morphological study using a light microscope and a scanning electron microscope showed the preservation of the structure of the biomaterial and more complete decellularization in samples subjected to lyophilization without prior impregnation with glycerol. The study of the Raman spectroscopy lines of a biopolymer made from a lyophilized amniotic membrane without preliminary impregnation with glycerin showed significant differences in the intensity of the spectral lines of amides, glycogen, and proline. Additionally, in these samples, the spectral lines of Raman scattering the characteristic of glycerol were not visualized; therefore, only biological substances characteristic of the native amniotic membrane have been preserved.

3D Bioprinting of Hyaline Articular Cartilage: Biopolymers, Hydrogels, and Bioinks.

The musculoskeletal system, consisting of bones and cartilage of various types, muscles, ligaments, and tendons, is the basis of the human body. However, many pathological conditions caused by aging, lifestyle, disease, or trauma can damage its elements and lead to severe disfunction and significant worsening in the quality of life. Due to its structure and function, articular (hyaline) cartilage is the most susceptible to damage. Articular cartilage is a non-vascular tissue with constrained self-regeneration capabilities. Additionally, treatment methods, which have proven efficacy in stopping its degradation and promoting regeneration, still do not exist. Conservative treatment and physical therapy only relieve the symptoms associated with cartilage destruction, and traditional surgical interventions to repair defects or endoprosthetics are not without serious drawbacks. Thus, articular cartilage damage remains an urgent and actual problem requiring the development of new treatment approaches. The emergence of biofabrication technologies, including three-dimensional (3D) bioprinting, at the end of the 20th century, allowed reconstructive interventions to get a second wind. Three-dimensional bioprinting creates volume constraints that mimic the structure and function of natural tissue due to the combinations of biomaterials, living cells, and signal molecules to create. In our case-hyaline cartilage. Several approaches to articular cartilage biofabrication have been developed to date, including the promising technology of 3D bioprinting. This review represents the main achievements of such research direction and describes the technological processes and the necessary biomaterials, cell cultures, and signal molecules. Special attention is given to the basic materials for 3D bioprinting-hydrogels and bioinks, as well as the biopolymers underlying the indicated products.

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects.

Reconstruction of critical-sized bone defects remains a tremendous challenge for surgeons worldwide. Despite the variety of surgical techniques, current clinical strategies for bone defect repair demonstrate significant limitations and drawbacks, including donor-site morbidity, poor anatomical match, insufficient bone volume, bone graft resorption, and rejection. Bone tissue engineering (BTE) has emerged as a novel approach to guided bone tissue regeneration. BTE focuses on in vitro manipulations with seed cells, growth factors and bioactive scaffolds using bioreactors. The successful clinical translation of BTE requires overcoming a number of significant challenges. Currently, insufficient vascularization is the critical limitation for viability of the bone tissue-engineered construct. Furthermore, efficacy and safety of the scaffolds cell-seeding and exogenous growth factors administration are still controversial. The in vivo bioreactor principle (IVB) is an exceptionally promising concept for the in vivo bone tissue regeneration in a predictable patient-specific manner. This concept is based on the self-regenerative capacity of the human body, and combines flap prefabrication and axial vascularization strategies. Multiple experimental studies on in vivo BTE strategies presented in this review demonstrate the efficacy of this approach. Routine clinical application of the in vivo bioreactor principle is the future direction of BTE; however, it requires further investigation for overcoming some significant limitations.

Biopolymer Material from Human Spongiosa for Regenerative Medicine Application.

Natural biopolymers demonstrate significant bone and connective tissue-engineering application efficiency. However, the quality of the biopolymer directly depends on microstructure and biochemical properties. This study aims to investigate the biocompatibility and microstructural properties of demineralized human spongiosa Lyoplast® (Samara, Russian Federation). The graft's microstructural and biochemical properties were analyzed by scanning electron microscopy (SEM), micro-computed tomography, Raman spectroscopy, and proteomic analysis. Furthermore, the cell adhesion property of the graft was evaluated using cell cultures and fluorescence microscopy. Microstructural analysis revealed the hierarchical porous structure of the graft with complete removal of the cellular debris and bone marrow components. Moreover, the proteomic analysis confirmed the preservation of collagen and extracellular proteins, stimulating and inhibiting cell adhesion, proliferation, and differentiation. We revealed the adhesion of chondroblast cell cultures in vitro without any evidence of cytotoxicity. According to the study results, demineralized human spongiosa Lyoplast® can be effectively used as the bioactive scaffold for articular hyaline cartilage tissue engineering.

PLA-PEG Implant as a Drug Delivery System in Glaucoma Surgery: Experimental Study.

Excessive postoperative scarring halts the effectiveness of glaucoma surgery and still remains a challenging problem. The purpose of this study was to develop a PLA-PEG-based drug delivery system with cyclosporine A or everolimus for wound healing modulation. METHODS: PLA-PEG implants saturation with cyclosporine A or everolimus as well as their further in vitro release were analyzed. Anti-proliferative activity and cytotoxicity of the immunosuppressants were studied in vitro using human Tenon's fibroblasts. Thirty-six rabbits underwent glaucoma filtration surgery with the application of sham implants or samples saturated with cyclosporine A or everolimus. The follow-up period was six months. A morphological study of the surgery area was also performed at seven days, one, and six months post-op. RESULTS: PLA-PEG implants revealed a satisfactory ability to cumulate either cyclosporine A or everolimus. The most continuous period of cyclosporine A and everolimus desorption was 7 and 13 days, respectively. Immunosuppressants demonstrated marked anti-proliferative effect regarding human Tenon's fibroblasts without signs of cytotoxicity at concentrations provided by the implants. Application of PLA-PEG implants saturated with immunosuppressants improved in vivo glaucoma surgery outcomes. CONCLUSIONS: Prolonged delivery of either cyclosporine A or everolimus by means of PLA-PEG implants represents a promising strategy of wound healing modulation in glaucoma filtration surgery.

Raman Spectroscopy for Assessment of Hard Dental Tissues in Periodontitis Treatment.

The objective of this work was to use Raman spectroscopy to assess hard dental tissues after professional oral hygiene treatment and curettage. Spectral changes were identified, and the discriminant model of the specific changes of intensity of the Raman lines (i.e., of dentin, cementum, and enamel), before and after the dental procedures, was developed. This model showed that 6 weeks after the procedures, the hard dental tissues did not have differences and, thus, provided similar conditions for bio-film and dental plaque formation, tissue repair, and new attachment to the surface of the root.

Raman Spectroscopy of Changes in the Tissues of Teeth with Periodontitis.

The results of experimental studies of the tissues of teeth with periodontitis, using the Raman spectroscopy method, are presented in this work. Spectral changes in the tissues of teeth with periodontitis were identified, and the results can be used for the correction of treatment of this disease in dental practice. Criteria for the noninvasive diagnosis of periodontitis, based on changes in tooth enamel spectral properties, were developed.

Assessment of decellularization of heart bioimplants using a Raman spectroscopy method.

We report the results of experimental studies on cardiac implants using a Raman spectroscopy method (RS). Raman spectra characteristics of leaves and walls of cardiac implants were obtained; the implants were manufactured by protocols of detergent-enzymatic technique (DET) and biological, detergent-free (BIO) decellularization, using detergents (group DET) or a detergent-free, nonproteolytic, actin-disassembling regimen (BIO). There were input optical coefficients that allowed us to carry out evaluation of the protocols of DET and BIO decellularization on the basis of the concentrations of glycosaminoglycans, proteins, amides, and DNA. It was shown that during DET and BIO decellularization, composition aberrations of proteins and lipids do not occur and the integrity of the collagenous structures is preserved. It was found that during the DET decellularization, preservation of glycosaminoglycans is better than during BIO decellularization.