Aim: To determine the association of anthropometric indicators with the severity of dysplastic phenotype in the age group of 14–18 years.Material and Methods. An anthropometric survey of 382 volunteers was conducted according to the recommendations of Norton, Kevin on 54 indicators. Anthropometric numerical data of individual traits, as well as the calculated percentage and absolute amount of fat, muscle and bone components, and, accordingly, the coefficients of the predominance of ecto-, meso- and endomorphic components in the somatotype structure and indices were processed by methods of variational statistics to obtain averages. The analysis of indicators of physical development of adolescents (height for age, body mass index (BMI) for age) was carried out in accordance with the methodological recommendations of the World Health Organization on the Z-score system using the software “WHO AnthroPlus” v.1.0.4. for children 5–19 years old. The degree of severity of the phenotypic signs of undifferentiated connective tissue dysplasia (UCTD) was formed according to the point system, taking into account the presence of professional sports in the daily life of volunteers in the past and present.Results. The minimum severity of the dysplastic phenotype was registered in 20% of cases, the average – in 25% of the examined, pronounced signs of UCTD were observed in 55% of boys and girls. In the structure of anthropometric data, the indicators characterizing UCTD were revealed, especially with a pronounced degree of manifestation: high growth, an increase in chest circumference, the ratio of hand to height, foot to height and arm span to height (p < 0.05). Among the surveyed with pronounced signs of UCTD, 59% were engaged in professional sports, namely high-static, medium-dynamic disciplines (gymnastics, figure skating, volleyball, light and weightlifting). In the vector analysis of the components of the catfish examined with an average degree (7–14 points) and a pronounced UCTD phenotype (more than 14 points) are characterized by large endomorphy and mesomorphy indices (p < 0.05). With an increase in the severity of the UCTD phenotype, an increase in the number and change in the quality of associations of the average score of the scale of phenotypic manifestations with anthropometric parameters was registered.Conclusion. The wide prevalence of phenotypic signs of UCTD in a representative sample of children and adolescents in Tomsk was revealed. The relationship between the frequency of the main signs of UCTD and physical activity has been established. The constitutional features of the physique of persons with preclinical manifestations of UCTD are determined. Associations of the degree of severity of the UCTD phenotype with anthropometric parameters have been recorded. Taking into account the fact of genotypic conditioning of the physique and the hereditary nature of the dysplastic phenotype, as well as the data obtained, an anthropometric examination with the identification of the somatotype can be offered as a screening of UCTD.

Polikaprolakton kak material pri sozdanii nanokompozitnyh struktur dostatochno izuchen s pozicii terapevticheskogo effekta i bezopasnosti primeneniya. Odnako ego biosovmestimost' v vide ob"emnyh makrokamer-nositelej ostaetsya predmetom diskussii vvidu izmeneniya sposoba 3D-pechati. Cel'yu raboty bylo opredelit' biosovmestimost' diffuzionnoj kamery iz polikaprolaktona pri ee implantacii na bedrennyj sosudisto-nervnyj puchok krysy. Issledovanie provodili na polovozrelyh krysah-samcah linii Wistar. ZHivotnym gruppy 1 (eksperimental'naya, n = 4) provodili implantaciyu diffuzionnoj kamery iz polikaprolaktona na bedrennyj sosudisto-nervnyj puchok. V gruppu 2 (kontrol'naya, n = 3) voshli intaktnye krysy. V hode makroskopicheskoj ocenki ne bylo vyyavleno patologicheskih izmenenij na meste implantacii i v organah-mishenyah. Pri mikroskopii tkanej ne vyyavleno sistemnoj reakcii, kolichestvo dvuyadernyh gepatocitov sostavilo 1,05%. Pokazateli stromal'no-parenhimatoznogo otnosheniya sostavili: pechen' — 1/33,20, nadpochechniki — 1/19,53, pochki — 1/23,65, selezenka — 1/26,52. Na 40-e sutki kartina krovi vklyuchala v sebya povyshenie chisla limfocitov na 4%, umen'shenie segmentoyadernyh nejtrofilov na 17% i monocitov na te zhe 17%. Eti rezul'taty podtverzhdayut bezopasnost' ispol'zovaniya diffuzionnoj kamery iz polikaprolaktona i ee biosovmestimost' pri postanovke na krupnye sosudistno-nervnye puchki, odnako vliyanie produktov biodegradacii polikaprolaktona trebuet bolee shirokogo issledovaniya pri bolee dlitel'nyh srokah biointegracii.

Macroencapsulation of cells allows to isolate the donor biomaterial from the influence of the recipient’s organism. The degree of isolation can vary from mechanical isolation of donor cells within the implantation site to complete immune isolation of the transplanted biological material. The diffusion chamber was the first device used for macroencapsulation. The initial stage of research of this technique was aimed at expanding the range of cell and tissue implantation in allogenic and xenogenic models and clarifying the mechanisms underlying the graft rejection reaction. Later the design of the diffusion chamber underwent a number of changes that determined the modern application of the macroencapsulation method. The derivative of the diffusion chamber – the engineering chamber in complex with the arterio-venous shunt is used as a tissue modeling tool for creation of soft tissue flaps of different composition with the axial type of blood supply. An alternative design of the flow chamber allows the formation of soft tissue flaps on intact vessels. The engineering chamber is also used for growing various types of tissues and organ fragments (cardiac transverse striated muscle tissue, lymphoid tissue, fragments of liver, thymus, pancreas). A separate direction in studying the range of practical applications of the diffusion chamber is the development and testing of methods of transplantation of pancreatic islet cells into animals when creating allo- and xenogeneic experimental models for the treatment of diabetes mellitus. Some devices are already undergoing clinical trials and are available as a product for experimental studies.

The aim of the study was to investigate local biocompatibility and systemic effects of nonwoven polylactide (PLA) matrices on blood and liver parameters after their subcutaneous implantation in Wistar rats.Materials and methods. Bioabsorbable fibrous PLA matrices were produced by electrospinning and had dimensions (10 × 10 mm², thickness of no more than 0.5 mm; fiber diameter in the matrix ~1 μm) appropriate for subcutaneous implantation in white laboratory rats. Polymer implants were sterilized in ethylene oxide vapor. Thirty days after the implantation of PLA matrices, local biocompatibility according to GOST ISO 10993-6-2011, cellular parameters (total leukocyte count, hemogram, erythrocyte count, hemoglobin concentration), and biochemical blood parameters (lactate concentration, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels) were studied, and a standard histologic evaluation of the liver was performed.Results. PLA matrix samples were mild local irritants on a scale of 1–1.9 points according to GOST ISO 10993-6-2011 criteria 30 days after the subcutaneous implantation. The median density of distribution of multinucleated giant cells (MNGCs) in the connective tissue around and in PLA matrices was 1,500 (1,350; 1,550) per 1 mm² of a slice. Pronounced leukocytic reaction due to lymphocytosis was noted (an increase by 1.7 times compared with a sham-operated (SO) control group, р < 0.02). The absence of a significant neutrophil count in the blood revealed sterile inflammation proceeding in the subcutaneous tissue around the PLA materials. Normalization of hepatic cytolysis markers (ALT and AST activity) in the blood without pronounced changes in the structure of the liver and the number of binuclear hepatocytes was noted. These markers were increased in SO controls (ALT up to 123% and AST up to 142%, p < 0.001 compared with values in the intact group).Conclusion. Nonwoven PLA matrices are biocompatible with subcutaneous tissue, undergo bioresorption by MNGCs, and have a distant protective effect on the functional state of the liver in laboratory animals. Hypotheses on the detected systemic effect during subcutaneous implantation of PLA matrices were discussed; however, specific mechanisms require further study.

The purpose of the study is to evaluate the cellular and molecular parameters of bone remodeling in the blood as potential markers of undifferentiated forms of connective tissue dysplasiaMaterials and methods. The structural and functional status of cellular elements of in vitro culturing of mononuclear leukocytes of peripheral blood in adolescent athletes connected with phenotypic manifestations of undifferentiated connective tissue dysplasia (UCTD) were investigated. 25 pupils of sport schools from 10–14 years old (main disciplines: figure skating, gymnastics, athletics) were examined with the help of express analysis. The average age of the examined adolescents was (12,0 ± 1,7) years. Clinical examination of adolescents allowed ranking the UCTD signs on a scale of 4–11,5 points.Results. A comparison of questionnaire survey results and an evaluation of bone remodeling distant markers allowed the revelation of 2 groups in the distribution of adolescent athletes: those with minimal signs of UCTD (scores lesser than 7 points – 10 pupils), and those with expressed UCTD phenotype (scores are equal or more than 7 points –15 pupils). Significant statistical decrease in the content of collagen type I degradation products (CrossLaps) (by 80%) and ionized calcium (by 5%) has been determined in the peripheral blood of adolescent athletes with expressed UCTD phenotype. In conditions of short-term 72-h cultivation of mononuclear leukocytes in the presence of a 3D matrix imitating the properties of the mineral substance of the regenerating bone tissue, morphofunctional features of cellular reaction in adolescent athletes with clinical manifestations of UCTD, as well the heterogeneity of the cell population associated with the appearance of cells with an osteoblast-like phenotype in the blood have been revealed. The results of investigation propose the use of distant cellular and molecular parameters of bone remodeling to screen the mechanisms and dynamics of dysplastic disorders in adolescent athletes.

Jurkat tat cell line reaction on short-term (24 h) in vitro contact with model composite implants designed for bone tissue bioengineering has been studied. The titanium samples was coated by thin nanostructured calcium phosphate (CaP) layer was formed by rf-magnetron sputtered deposition. An increase in the number of leukemic line T-lymphoblasts presented CD124, CD25, CD4, CD8, CD16/56 markers of cell maturation and differentiation has been revealed with the help of Wilcoxon T-test. In a case of CD8 positive cells the differences reached to statistic levels (Mann—Whitney U -test) as compared with cells had no contact with model implants. No implants effect was mediated by cytokines secretion (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10 and TNFα). An elevation of apoptotic and necrotic cells number has been not revealed. Silicone incorporation into CaP composition had no essential modulating action on indices studied. A conclusion about an absence of immunotoxic effect of investigated coatings as regards to T-cell immunity has been made. In vitro acceleration of CD8 presentation by human T-lymphoblasts may be conditioned by their direct interaction with artificial CaP surfaces.

Activities of total alkaline phosphatase (TALP) and its bone isoform (BALP) was greater in groups of children and adolescents in the late posttraumatic period (pattern of reparative bone remodeling) and scoliosis (pathological bone remodeling), than in the control (healthy children and adolescents). The content of collagen type I degradation products (CrossLaps) peripheral blood practically was unchanged. Examined group with posttraumatic period had high activity of tartrate-resistant acid phosphatase form (TRACP). TALP activity reached minimum values in all the studied groups. In the process of children growing to 15–18 years old, as compared to 7–10 years old, reducing activity of remodeling was observed under physiological (healthy donors) and reparative osteogenesis. It’s changes was recorded by significant decrease of the studied indicators. On the contrary, children 15–18 years old with scoliosis had maximum of the imbalance (activation/inhibition of various signs of osteogenesis) of resorptive/synthetic bone processes. Also, for this group we discovered decrease osteocalcin concentration of 4 times in comparison with the group children of 7–10 years old. The detected growth of the correlations number in the correlation matrix of bone remodeling markers in case of scoliosis proposes the reduction of adaptation reserve of 15–18 years old adolescents, suffering from dysplasia of connective tissue. Thus, the pathophysiological and clinical significance of distant markers of bone metabolism screening in peripheral blood the is ambiguous. The interpretation of these indicators is difficult and largely depends on the clinical situation and age of patients. This requires improving the diagnostic approach to assess physiological and pathological remodeling of bone tissue by means of biochemical blood indicators.

Activities of total alkaline phosphatase (TALP) and its bone isoform (BALP) was greater in groups of children and adolescents in the late posttraumatic period (pattern of reparative bone remodeling) and scoliosis (pathological bone remodeling), than in the control (healthy children and adolescents). The content of collagen type I degradation products (CrossLaps) peripheral blood practically was unchanged. Examined group with posttraumatic period had high activity of tartrate-resistant acid phosphatase form (TRACP). TALP activity reached minimum values in all the studied groups. In the process of children growing to 15–18 years old, as compared to 7–10 years old, reducing activity of remodeling was observed under physiological (healthy donors) and reparative osteogenesis. It’s changes was recorded by significant decrease of the studied indicators. On the contrary, children 15–18 years old with scoliosis had maximum of the imbalance (activation/inhibition of various signs of osteogenesis) of resorptive/synthetic bone processes. Also, for this group we discovered decrease osteocalcin concentration of 4 times in comparison with the group children of 7–10 years old. The detected growth of the correlations number in the correlation matrix of bone remodeling markers in case of scoliosis proposes the reduction of adaptation reserve of 15–18 years old adolescents, suffering from dysplasia of connective tissue. Thus, the pathophysiological and clinical significance of distant markers of bone metabolism screening in peripheral blood the is ambiguous. The interpretation of these indicators is difficult and largely depends on the clinical situation and age of patients. This requires improving the diagnostic approach to assess physiological and pathological remodeling of bone tissue by means of biochemical blood indicators.

Strontium ranelate (29 μg/ml) and ibandronic acid (50 μM) produced a cytotoxic effect on rat bone marrow myelokaryocytes in vitro . Strontium ranelate increased the number of myelokaryocytes with signs of necrosis, ibandronic acid increased the number of apoptotic and necrotic cells in the 9-day 2D culture of bone marrow cells on the plastic surface of the wells of culture plates. Co-culturing of the bone marrow with 3D matrices with microarc calcium phosphate coating that simulated bone mineral matrix increased intracellular ROS concentration, but abolished the cytotoxic effect of these drugs.

Strontium ranelate (SR) effect on the functional parameters of human blood mononuclear leukocytes culture has been investigated. SR in concentrations of 2.9, 29, and 290 mg/ml produces a dose-dependent decrease in the activity of alkaline phosphatase and the content of calcium and potassium ions in supernatants. In concentrations of 2.9 and 29 mg/ml, SR decreases, while in a concentration of 290 mg/ml it increases the intercellular phosphate ion content. Fibroblast- and osteoblast-like cells, which are capable of regulating mineral compound of intercellular liquid, are SR cellular targets in human blood mononuclear leukocytes culture.

In order to evaluate cytogenetic effect of nanocomposite materials used in traumatology and orthopedics an investigation of chromosomal aberration ins in the culture of lymphocytes short-term contacted with artificial material (nanostructured titanium samples of implants bearing bilateral calcium phosphate coating) in patients with dysplasia of connective tissue (DCT) and osteogenesis imperfecta (OI) has been conducted. A reduction of percent of aberrant cells having single or/and paired chromosomal breaks as compared with spontaneous mutagenesis (without model samples) was revealed under introduced biocompatible composites into blood cell cultures of patients with DCT or OI. Analysis of frequency and spectrum of chromosomal aberrations in blood cells can be considered as potential prognostic criterion and a predictor of implant’s efficacy in the surgical treatment of DCT and OI complications.

Изучены секреция цитокинов, апоптоз и продукция активных форм кислорода в клеточных культурах при их контакте in vitro с имплантатами, несущими микродуговые, магнетронные или абляционные кальцийфосфатные покрытия. Установлено, что клетками, способными контролировать процессы приживления/отторжения имплантатов с разной шероховатостью, являются, в первую очередь, мононуклеарные лейкоциты крови. Тесты in vitro подтвердили факт, что имплантаты с «гладкими» ( Ra менее 1 мкм) кальцийфосфатными покрытиями менее пригодны для стимуляции репаративной регенерации костной ткани.

An influence relief features and quantitative parameters of model bone mineral matrix on in vitro morphofunctional status of human prenatal stromal lung cells (HPSLC) and in vivo mice bone/marrow system remodeling has been studied. Investigations have showed that magnetron calcium phosphate (CaP) coatings are thin (thickness less than 1—2 μm), nonporous, smooth (Ra < 1 μm) layer of carboxylated apatites with the calcium/phosphorus ratio higher than stoichiometric one (more than 1.67). Such 2D surfaces have discreet structure-functional microterritories (niches) for HPSLC. Nevertheless, HPSLC maturation in osteoblasts under 4-days cultivation on such surfaces is unlikely. Poor HPSLC osteogenic committing on «smooth» (Ra < 1 μm) CaP coating is in vitro associated with an average index of artificial osteogenic niche less than 34%, weak artificial surface dissolution and elevated TNFα secretion by cell culture. A behavior of such implants with singenic bone marrow column is displayed in vivo by a degeneration of mice heterotopic osteogenesis and hemopoiesis. Methodology suggested allows apparently to imitate bone surface microterritories having “quiescent“ endosteal niches for stromal and hemopoietic stem cells.

Purpose: to study the effect of the phase structure artificial calcium – phosphatic surfaces on an osteogenic differentiation of stromal stem cells in vivo on implants with the fixed range of roughness. Materials and methods. The condition of the surface was estimated by means of the measuring system Talysurf 5-120, phase structure – by the diffractometer Shimadzu XRD-7000 (Japan), element structure – by the electron microscope of Hitachi S5500. An implant from the titan of the VT1.0 brand (diameter of 12 mm, thickness of 1 mm) with the rough calcium phosphate coating applied by microarc oxidation with a column of bone marrow has been hypodermically placed to 35 mice males of the CBA/CaLac line. Histological research was carried out in 45 days. The quantitative parameters of grown tissue plates were defined by the computer morphometry. Results. The growth of coarse-fibered bone tissue with the cavities filled by red marrow has been revealed on plates with artificial surfaces. Its reproducibility was 22 % higher on surfaces composed of tricalcium phosphate and hydroxylapatite compared with amorphous calcium phosphate.

The use of intramedullary bioactive osteosynthesis combined with the Ilizarov fixator contributes to correction of skeletal deformities, allows to put patients with osteogenesis imperfecta on their feet. The morphofunctional parameters of culture of peripheral blood mononuclear cells can be considered as the probable markers and predictors of osteogenesis imperfecta process and duration of patients’ rehabilitation.

The use of intramedullary bioactive osteosynthesis combined with the Ilizarov fixator contributes to correction of skeletal deformities, allows to put patients with osteogenesis imperfecta on their feet. The morphofunctional parameters of culture of peripheral blood mononuclear cells can be considered as the probable markers and predictors of osteogenesis imperfecta process and duration of patients’ rehabilitation.

Jurkat tat cell line reaction on short-term (24 h) in vitro contact with model composite implants designed for bone tissue bioengineering has been studied. The titanium samples was coated by thin nanostructured calcium phosphate (CaP) layer was formed by rf-magnetron sputtered deposition. An increase in the number of leukemic line T-lymphoblasts presented CD124, CD25, CD4, CD8, CD16/56 markers of cell maturation and differentiation has been revealed with the help of Wilcoxon T-test. In a case of CD8 positive cells the differences reached to statistic levels (Mann—Whitney U-test) as compared with cells had no contact with model implants. No implants effect was mediated by cytokines secretion (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10 and TNFα). An elevation of apoptotic and necrotic cells number has been not revealed. Silicone incorporation into CaP composition had no essential modulating action on indices studied. A conclusion about an absence of immunotoxic effect of investigated coatings as regards to T-cell immunity has been made. In vitro acceleration of CD8 presentation by human T-lymphoblasts may be conditioned by their direct interaction with artificial CaP surfaces.

Cytokine secretion, apoptosis and production of active oxygen forms in cell cultures for their in vitro contact with implants carrying microarc, magnetron or ablation calcium-phosphate coatings have been studied in the work. Mononuclear blood leukocytes have been established to be first of all cells regulating the acceptance/rejection of implants with different roughness. Implants with “smooth” calcium-phosphate coatings are less suitable for bone tissue reparative regeneration.

In our opinion, determination of the levels of RANTES-CCR5 system expression on blood mononuclear leucocytes in vitro can be used for individual evaluation of the perspective of implant material as inflammatory/osteoinductive reaction trigger in patients with osteogenesis imperfecta (OI). Besides, RANTES gene expression on blood mononuclear leucocytes may be effective in the development of the methods to predict the degree of inflammatory (osteolytic) response, while CCR5 gene expression in the development of the methods to predict the process of reparative bone tissue remodeling in response to using different implants.