Bisphosphonates are chemical analogs of isoprene lipids, which competitively decrease the activity of farnesyl diphosphate synthase in osteoclasts and thus retard prenylation. The non-prenylated small GTPases cannot attach to the membrane of osteoclasts, which decreases their resorptive function and accelerates apoptosis. Strontium ranelate activates the Wnt signal pathway (with participation of calcium-sensitive receptor), increases the replication activity (by changing the function of RANKL/RANK/OPG system) thus suppressing the apoptosis of osteoblasts, and retards the resorptive function by accelerating the apoptosis of osteoclasts.

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.

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.

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.

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.

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 vitro modeling of molecular reactions of peripheral blood mononuclear leukocytes to contact with implants which are perspective for improvement of osteosynthesis techniques can be used, in our opinion, for prognostic estimation of acceptance/rejection of artificial materials and the prospective usage for surgical treatment of patients with osteogenesis imperfecta and connective tissue dysplasia.

Ferreed nanoparticles based on the ferro-magnetite nanocomposites were prepared by electric-spark dispersion method and tested for physicochemical behavior. The most efficacy in doxorubicin adsorption (by chemical adsorption mechamsm) was shown for nanoparticles, which were prepared by sputter-ion method in hexane solution. These nanoparticles was appeared to be able to form the tumor cell bound agglomerates that indicate their tropism to tumor and evidence of doxorubicin deliver to cancer cells. We have found marked cytolytic action of doxorubicin bound nanoparticles against Ehrlich adenocarcinoma tumor cells in vitro. Data obtained point the perspectives for father investigation to elaborate ferreed nanoparticles as potential vectors for drug-delivery application.