Bone Tissue Remodeling Research Articles

MORPHOLOGICAL AND RADIOLOGICAL ASPECTS OF MANDIBULAR BONE REMODELLING AFTER ACTIVATED CHITOSAN IMPLANTATION

Introduction. Bone regeneration remains a complex and challenging area for modern medicine. This study aims to provide a comprehensive understanding of the dynamics of bone tissue remodeling after defect creation and filling with chitosan-based osteoplastic material. While osteoplastic materials are widely used clinically, and chitosan offers unique properties, its impact on maxillofacial bone regeneration, particularly the underlying mechanisms and dynamics, is not fully understood and requires further clarification and detailed investigation. Aim: this study aims to determine and compare the morphological, radiological, and lectin-histochemical characteristics of osteoregeneration after the transplantation of activated chitosan (Chitosan-A) into an experimental defect in the rabbit mandible. Materials and methods. The study was carried out on mature male rabbits aged 6-7 months, weighing 2.5-3 kg. The control group included animals with a bone tissue defect that healed under a blood clot. The experimental group consisted of rabbits in which the bone defect was filled with activated chitosan (Chitosan-A). The post-traumatic state of bone tissue in the defect area was monitored over a period of 84 days using the following methods: bone defect modeling, assessment of jaw macrostructure, radiographic examination, radiovisiography, microscopic analysis of bone sections, and lectin-histochemical analysis of decalcified bone sections. Results. Examination of the macrostructure of the experimental bone defect in the rabbit mandible, following the implantation of chitosan activated with acetic acid (Chitosan-A) into the defect cavity, revealed extensive regenerative changes associated with injury recovery. These findings correlated with data obtained from radiographic and radiovisiographic examinations. Microscopic analysis of bone sections demonstrated a staged progression of regenerative changes and provided insights into the composition of the regenerate. Conclusions. The use of Chitosan-A was shown to modulate tissue development and remodeling throughout the experiment. Bone density in the experimental group approached normal levels, being only 10.2% lower than in the control group at the end of the study. Microscopic examination revealed bone tissue remodeling with incomplete geometry of newly formed osteons and residual traces of the Chitosan-A material.

Some aspects of the development of musculoskeletal pathology in children in an industrial center with a city-forming enterprise for the production of non-ferrous metal alloys

Introduction. At present, incidence of musculoskeletal diseases is growing in children, especially in areas with poor quality of the environment The purpose of the study was to identify markers of the development of musculoskeletal pathology in children to minimize the risk of health under conditions of exposure to emissions from a non-ferrous metal alloy production plant. Materials and methods. We performed clinical examination in four hundred ninety five 5 and 7 years children (54.3% boys and 45.7% girls). They lived in a large industrial center where safe standards for chemical in ambient air were violated per aluminum (up to 3.06 average daily MPL) and gaseous fluorides (up to 8.25 average daily MPL). Also, we examined 95 children (57.9% boys and 42.1% girls) who lived in an area where the foregoing chemicals were detected in ambient air in levels not exceeding 0.3–0.54 average daily MPL. The children were examined by pediatrician. Levels of aluminum and fluoride-ion were determined in urine. We examined phosphor-calcium metabolism indices and markers of bone tissue synthesis and resorption. The study also involved performing ultrasound densitometry. Results. The children form the observation group had aluminum and fluoride-ion levels in their urine up to 3.2 times a higher than their peers from the reference group. Likelihood of musculoskeletal pathology, including deforming dorsopathy, was found to be up to 1.3 times higher for the exposed children. Bone metabolism failure manifested itself in the exposed children through elevated levels of ionized calcium in blood; elevated levels of N-osteocalcin in 25.4% of the exposed children and elevated activity of tartrate-resistant acid phosphatase in 59.3%. Bone marrow resorption was by 9.2 times more likely to be activated in the exposed children from a large industrial center. Impaired bone tissue remodelling was accompanied with lower bone mineral density in 54.7% of the exposed children. Limitations. The study was conducted on 5–7 years children. Conclusion. Markers of bone tissue metabolism disorders can be used to implement sanitary-epidemiological and medical-preventive measures to reduce the risk of developing osteopathic conditions in childhood.

Многофакторное снижение размерности (MDR-анализ) в генетических исследованиях

Based on the assumption that some gene variants in combination may show cumulative or epistatic effects, it is relevant to explore the combination of genotypes of independently acting and interacting polymorphic genes. The article describes the application of nonparametric method of multifactor dimensionality reduction (MDR) on a cohort of highly qualified athletes in order to determine the most preferable combination of genotypes of genes of neurotransmitter systems that determine the functioning of the higher nervous system. Based on the obtained data on the patterns of intergenic interactions, we performed cluster analysis showing the type of interaction between polymorphic loci of neurotransmitter system genes. In addition, we obtained models of the most favorable combination of genotypes for cyclic and acyclic sports. The MDR method in our researches was also applied to identify the unfavorable combination of genotypes in the development of such pathologies as nephropathy and disorder of bone tissue remodeling in young athletes.

Prospective directions in human health monitoring during long-term spaceflights

Introduction. The increasing duration of spaceflights and the associated prolonged exposure of space crewmembers to unfavorable microgravity conditions necessitate the development of improved approaches to diagnosing the health status directly during the flight. This study is aimed at searching and selecting promising biological markers suitable for studying directly during spaceflights.Objective. To review the current status of the abovementioned problem and to identify biochemical and molecular markers most promising for biomedical research in spaceflight conditions.Methods. A literature review of methods currently used for monitoring the level of biological markers characterizing variations in the immune, excretory, reproductive, musculoskeletal, and blood coagulation systems caused by spaceflight conditions was carried out.Findings. Data concerning biological markers used for monitoring the health status of space crewmembers were analyzed. The authors argue that protein markers reflecting bone tissue remodeling hold particular promise. The decrease in bone tissue density developed as a result of microgravity carries potential risks of traumatism, thus making screening diagnostics of the state of the musculoskeletal system a key focus of laboratory diagnostics. The conducted literature review suggests that P1NP and osteocalcin may serve as the most informative markers of new bone tissue formation, while collagen C-telopeptide, pyridine cross-links, and tartrate-resistant acid phosphatase may serve as markers of bone tissue lysis.

Ridge preservation using octacalcium phosphate collagen to induce new bone containing a vascular network of mainly Type H vessels

Many studies have shown that it is important to use bone grafts that are easy to mold, bioabsorbable, and stable over time. We focused on Type H blood vessels, which were discovered by Kusumbe et al. in 2014 to be responsible for the interaction between angiogenesis and osteogenesis. The aim of this study was to assess the effect of octacalcium phosphate collagen (OCP/Col), on the healing processes of the extraction socket and the alveolar bone surrounding the extraction socket. Ridge preservation of rat lower first molars was conducted using OCP/Col, and a series of experiments involving micro-CT scanning, observations of new bone, bone morphometry measurements, histological and immunohistochemical analyses, and second harmonic generation imaging were conducted to analyze bone mass, bone quality, angiogenesis, and mechanical properties. The results demonstrate that the calcification level was not very high when using OCP/Col for RP. Moreover, the newly formed bone is rich in vascular components and collagen fibers that are essential for bone tissue remodeling. These characteristics of OCP/Col in RP could contribute significantly to the construction of a rich vascular network around dental implants immediately after implant placement and the subsequent acquisition of osseointegration and reconstruction of the surrounding tissue.

Pre-vascularized porous gelatin-coated β-tricalcium phosphate scaffolds for bone regeneration: an in vivo and in vitro investigation.

Vascularization is vital in bone tissue engineering, supporting development, remodeling, and regeneration. Lack of vascularity leads to cell death, necessitating vascularization strategies. Angiogenesis, forming new blood vessels, provides crucial nutrients and oxygen. Pre-vascularized gelatin-coated β-tricalcium phosphate (G/β-TCP) scaffolds show promise in bone regeneration and vascularization. Our study evaluates G/β-TCP scaffolds' osteogenic and angiogenic potential in vitro and a canine model with vascular anastomosis. Channel-shaped G/β-TCP scaffolds were fabricated using foam casting and sintering of a calcium phosphate/silica slurry-coated polyurethane foam, then coated with cross-linked gelatin. Buccal fat pad-derived stem cells (BFPdSCs) were seeded onto scaffolds and assessed over time for adhesion, proliferation, and osteogenic capacity using scanning electron microscopy (SEM), 4,6-diamidino-2-phenylindole (DAPI) staining, Alamar blue, and alkaline phosphatase (ALP) assays. Scaffolds were implanted in a canine model to evaluate osteogenesis and angiogenesis by histology and CT scans at 12 wk. Our studies showed preliminary results for G/β-TCP scaffolds supporting angiogenesis and bone regeneration. In vitro analyses demonstrated excellent proliferation/viability, with BFPdSCs adhering and increasing on the scaffolds. ALP activity and protein levels increased, indicating osteogenic differentiation. Examination of tissue samples revealed granulation tissue with a well-developed vascular network, indicating successful angiogenesis and osteogenesis was further confirmed by a CT scan. In vivo, histology revealed scaffold resorption. However, scaffold placement beneath muscle tissue-restricted bone regeneration. Further optimization is needed for bone regeneration applications.

Mechanobiological cues to bone cells during early metastasis drive later osteolysis: a computational mechanoregulation framework prediction

Bone cells contribute to tumour metastasis by producing biochemical factors that stimulate tumour cell homing and proliferation, but also by resorbing bone matrix (osteolysis) that releases further stimulatory factors for tumour growth in a vicious cycle. Changes in the local mechanical environment of bone tissue occur during early metastasis, which might activate mechanobiological responses by resident bone cells (osteocytes) to activate resorption (osteoclasts) and thereby contribute to tumour invasion. The objective of this study is to investigate whether bone osteolysis is driven by early changes in the bone mechanical environment during metastasis by (a) implementing subject-specific FE models of metastatic femora to predict the mechanical environment within bone tissue during early metastasis (3-weeks after tumour inoculation) and then (b) applying mechanoregulation theory to predict bone tissue remodelling as a function of the evolving mechanical environment within bone tissue during breast cancer-bone metastasis. We implemented a global resorption rate derived from an experimental model, but the mechanoregulation algorithm predicted localised bone loss in the greater trochanter region, the same region where osteolysis was prevalent after three weeks of metastasis development in the animal model. Moreover, the mechanical environment evolved in a similar manner to that reported in separate subject-specific finite element models of these same animals by 6 weeks. Thus, we propose that early changes in the physical environment of bone tissue during metastasis may elicit mechanobiological cues for bone cells and activate later osteolytic bone destruction.

PIEZO1 variants that reduce open channel probability are associated with familial osteoarthritis.

The synovial joints senses and responds to a multitude of physical forces to maintain joint homeostasis. Disruption of joint homeostasis results in development of osteoarthritis (OA), a disease characterized by loss of joint space, degeneration of articular cartilage, remodeling of bone and other joint tissues, low-grade inflammation, and pain. How changes in mechanosensing in the joint contribute to OA susceptibility remains elusive. PIEZO1 is a major mechanosensitive cation channel in the joint directly regulated by mechanical stimulus. To test whether altered PIEZO1 channel activity causes increased OA susceptibility, we determined whether variants affecting PIEZO1 are associated with dominant inheritance of age-associated familial OA. We identified four rare coding variants affecting PIEZO1 that are associated with familial hand OA. Single channel analyses demonstrated that all four PIEZO1 mutant channels act in a dominant-negative manner to reduce the open probability of the channel in response to pressure. Furthermore, we show that a GWAS mutation in PIEZO1 associated with reduced joint replacement results in increased channel activity when compared with WT and the mutants. Our data support the hypothesis that reduced PIEZO1 activity confers susceptibility to age-associated OA whereas increased PIEZO1 activity may be associated with reduced OA susceptibility.

Mechanisms of Spinal Metastases: New Perspectives

Metastases are considered to be a key mechanism for the spread of malignant tumors, whereby tumor cells separate from the primary site and form new tumor nodes in various parts of the body. Bone tissue, including the spine, is often affected by metastases, which can significantly worsen the prognosis and quality of life of patients. Metastasis comprises a complex multistep process during which tumor cells undergo molecular and phenotypic changes enabling them to migrate and adapt to new conditions in the body. Bone metastases can be osteolytic, causing bone destruction, or osteoblastic, stimulating excessive bone formation. Tumor cells enter the bone and activate osteoclasts or osteoblasts, thereby leading to remodelling of bone tissue and formation of a closed cycle of bone destruction and tumor growth. The characteristics of tumor cells are determined by their genetic and epigenetic changes, as well as interaction with the environment. Understanding the molecular and pathophysiological aspects of spinal metastasis is essential to developing effective treatments and improving therapeutic approaches. The paper considers new therapeutic approaches aimed at overcoming spinal metastasis in order to improve the prognosis and quality of life of patients.

Static magnetic field-induced IL-6 secretion in periodontal ligament stem cells accelerates orthodontic tooth movement

Static magnetic field (SMF) promoting bone tissue remodeling is a potential non-invasive therapy technique to accelerate orthodontic tooth movement (OTM). The periodontal ligament stem cells (PDLSCs), which are mechanosensitive cells, are essential for force-induced bone remodeling and OTM. However, whether and how the PDLSCs influence the process of inflammatory bone remodeling under mechanical force stimuli in the presence of SMFs remains unclear. In this study, we found that local SMF stimulation significantly enhanced the OTM distance and induced osteoclastogenesis on the compression side of a rat model of OTM. Further experiments with macrophages cultured with supernatants from force-loaded PDLSCs exposed to an SMF showed enhanced osteoclast formation. RNA-seq analysis showed that interleukin-6 (IL-6) was elevated in force-loaded PDLSCs exposed to SMFs. IL-6 expression was also elevated on the pressure side of a rat OTM model with an SMF. The OTM distance induced by an SMF was significantly decreased after injection of the IL-6 inhibitor tocilizumab. These results imply that SMF promotes osteoclastogenesis by inducing force-loaded PDLSCs to secrete the inflammatory cytokine IL-6, which accelerates OTM. This will help to reveal the mechanism of SMF accelerates tooth movement and should be evaluated for application in periodontitis patients.

Frailty: Focus on Regenerative Medicine

Frailty, as a specific condition of increased vulnerability and deterioration of general health associated with aging in the elderly, is an emerging problem worldwide with serious implications for clinical practice and public health. Frailty increases the risk of falls, hospitalization, disability, and death. Muscle aging is associated with progressive loss of skeletal muscle mass and function. Loss of muscle mass with age can be related to muscle fiber atrophy and loss of muscle fibers. With increasing human age, remodeling of bone tissue becomes more prone to slow and steady loss of bone mass, which is primarily associated with loss of bone formation by osteoblasts. Recent preclinical and clinical studies have confirmed the safety of mesenchymal stem/stromal cells (MSCs) in the treatment of frailty. MSCs are attracted to sites of damage where they act to reduce inflammation and promote cell repair. Thus, there is an assumption that frailty can be treated with cell therapy

Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration.

Stem cell-derived extracellular vesicles (EVs) show great potential for promoting bone tissue regeneration. However, normal EVs (Nor-EVs) have a limited ability to direct tissue-specific regeneration. Therefore, it is necessary to optimize the osteogenic capacity of EV-based systems for repairing extensive bone defects. Herein, we show that hydrogels loaded with osteoinductive dental pulp stem cell-derived EVs (Ost-EVs) enhanced bone tissue remodeling, resulting in a 2.23 ± 0.25-fold increase in the expression of bone morphogenetic protein 2 (BMP2) compared to the hydrogel control group. Moreover, Ost-EVs led to a higher expression of alkaline phosphatase (ALP) (1.88 ± 0.16 of Ost-EVs relative to Nor-EVs) and the formation of orange-red calcium nodules (1.38 ± 0.10 of Ost-EVs relative to Nor-EVs) in vitro. RNA sequencing revealed that Ost-EVs showed significantly high miR-1246 expression. An ideal hydrogel implant should also adhere to surrounding moist tissues. In this study, we were drawn to mussel-inspired adhesive modification, where the hydrogel carrier was crafted from hyaluronic acid (HA) and polyethylene glycol derivatives, showcasing impressive tissue adhesion, self-healing capabilities, and the ability to promote bone growth. The modified HA (mHA) hydrogel was also responsive to environmental stimuli, making it an effective carrier for delivering EVs. In an ectopic osteogenesis animal model, the Ost-EV/hydrogel system effectively alleviated inflammation, accelerated revascularization, and promoted tissue mineralization. We further used a rat femoral condyle defect model to evaluate the in situ osteogenic ability of the Ost-EVs/hydrogel system. Collectively, our results suggest that Ost-EVs combined with biomaterial-based hydrogels hold promising potential for treating bone defects.

A review on gold nanoparticles as an innovative therapeutic cue in bone tissue engineering: Prospects and future clinical applications

Bone damage is a complex orthopedic problem primarily caused by trauma, cancer, or bacterial infection of bone tissue. Clinical care management for bone damage remains a significant clinical challenge and there is a growing need for more advanced bone therapy options. Nanotechnology has been widely explored in the field of orthopedic therapy for the treatment of a severe bone disease. Among nanomaterials, gold nanoparticles (GNPs) along with other biomaterials are emerging as a new paradigm for treatment with excellent potential for bone tissue engineering and regenerative medicine applications. In recent years, a great deal of research has focused on demonstrating the potential for GNPs to provide for enhancement of osteogenesis, reduction of osteoclastogenesis/osteomyelitis, and treatment of bone cancer. This review details the latest understandings in regards to GNPs based therapeutic systems, mechanisms, and the applications of GNPs against various bone disorders. The present review aims to summarize i) the mechanisms of GNPs in bone tissue remodeling, ii) preparation methods of GNPs, and iii) functionalization of GNPs and its decoration on biomaterials as a delivery vehicle in a specific bone tissue engineering for future clinical application.

Cell-free chitosan/silk fibroin/bioactive glass scaffolds with radial pore for in situ inductive regeneration of critical-size bone defects

Tissue-engineered is an effective method for repairing critical-size bone defects. The application of bioactive scaffold provides artificial matrix and suitable microenvironment for cell recruitment and extracellular matrix deposition, which can effectively accelerate the process of tissue regeneration. Among various scaffold properties, appropriate pore structure and distribution have been proven to play a crucial role in inducing cell infiltration differentiation and in-situ tissue regeneration. In this study, a chitosan (CS) /silk fibroin (SF) /bioactive glass (BG) composite scaffold with distinctive radially oriented pore structure was constructed. The composite scaffolds had stable physical and chemical properties, a unique pore structure of radial arrangement from the center to the periphery and excellent mechanical properties. In vitro biological studies indicated that the CS/SF/BG scaffold could promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the expression of related genes due to the wide range of connected pore structures and released active elements. Furthermore, in vivo study showed CS/SF/BG scaffold with radial pores was more conducive to the repair of skull defects in rats with accelerated healing speed during the bone tissue remodeling process. These results demonstrated the developed CS/SF/BG scaffold would be a promising therapeutic strategy for the repair of bone defects regeneration.

The Role of Osteocytes in Pre-metastatic Niche Formation.

The formation of a pre-metastatic niche (PMN), in which primary cancer cells prime the distant site to be favorable to their engraftment and survival, may help explain the strong osteotropism observed in multiple cancers, such as breast and prostate. PMN formation, which includes extracellular matrix remodeling, increased angiogenesis and vascular permeability, enhanced bone marrow-derived cell recruitment and immune suppression, has mostly been described in soft tissues. In this review, we summarize current literature of PMN formation in bone. We also present evidence of a potential role for osteocytes to be the primary mediators of PMN development. Osteocytes regulate the bone microenvironment in myriad ways beyond canonical bone tissue remodeling, including changes that contribute to PMN formation. Perilacunar tissue remodeling, which has been observed in both bone and non-bone metastatic cancers, is a potential mechanism by which osteocyte-cancer cell signaling stimulates changes to the bone microenvironment. Osteocytes also protect against endothelial permeability, including that induced by cancer cells, in a loading-mediated process. Finally, osteocytes are potent regulators of cells within the bone marrow, including progenitors and immune cells, and might be involved in this aspect of PMN formation. Osteocytes should be examined for their role in PMN formation.

Regulator of G protein signalling 18 promotes osteocyte proliferation by activating the extracellular signal‑regulated kinase signalling pathway.

Osteocyte function is critical for metabolism, remodelling and regeneration of bone tissue. In the present study, the roles of regulator of G protein signalling 18 (RGS18) were assessed in the regulation of osteocyte proliferation and bone formation. Target genes and signalling pathways were screened using the Gene Expression Omnibus (GEO) database and Gene Set Enrichment Analysis (GSEA). The function of RGS18 and the associated mechanisms were analysed by Cell Counting Kit 8 assay, 5‑ethynyl‑2'‑deoxyuridine assay, flow cytometry, reverse transcription‑quantitative PCR, western blotting and immunostaining. Overlap analysis of acutely injured subjects (AIS) and healthy volunteers (HVs) from the GSE93138 and GSE93215 datasets of the GEO database identified four genes: KIAA0825, ANXA3, RGS18 and LIPN. Notably, RGS18 was more highly expressed in peripheral blood samples from AIS than in those from HVs. Furthermore, RGS18 overexpression promoted MLO‑Y4 and MC3T3‑E1 cell viability, proliferation and S‑phase arrest, but inhibited apoptosis by suppressing caspase‑3/9 cleavage. Silencing RGS18 exerted the opposite effects. GSEA of GSE93138 revealed that RGS18 has the ability to regulate MAPK signalling. Treatment with the MEK1/2 inhibitor PD98059 reversed the RGS18 overexpression‑induced osteocyte proliferation, and treatment with the ERK1/2 activator 12‑O‑tetradecanoylphorbol‑13‑acetate reversed the effects of RGS18 silencing on osteocyte proliferation. In conclusion, RGS18 may contribute to osteocyte proliferation and bone fracture healing via activation of ERK signalling.

Alterations in immunolocalisation of non-collagenous proteins in cartilage and bone tissue after gastrectomy, antrectomy and fundectomy in rat model

Bone, as a tissue, plays a pivotal role in maintaining whole body homeostasis, contributing to, among other things, structural support, blood cell production, and mineral storage. On the other hand, bone homeostasis depends on hormonal factors released by various tissues of the body, including the gastrointestinal tract. Thus, surgical procedures involving the removal of various parts of the stomach wall, such as, antrectomy and fundectomy or partial gastrectomy, may have profound negative effects on bone metabolism and mineralization. These effects may result from changes in the concentration of neuropeptides, such as nesfatin-1, secreted by cells located in the fundus and vestibule of the stomach. Additionally, bone morphogenetic proteins, osteocalcin, osteoprotegerin, and tissue inhibitor of metalloproteinases 2, are regulatory proteins involved in bone metabolism, playing a key role in maintaining the balance between the activity of osteoclasts and osteoblasts, cells responsible for the remodeling of bone tissue. The aim of this study was to investigate the effects of antrectomy, fundectomy, and partial gastrectomy, on bone homeostasis in a rat model. The experiment was carried out on 24 male Wistar rats randomly and equally divided into control (SHO), gastrectomy (GAST), antrectomy (ANT), and fundectomy (FUN) groups. At the beginning of the study, the rats underwent surgical removal of selected parts of the stomach. At the end of the 6-week study, the rats were sacrificed, and femurs were collected. Microscopic images of immunohistochemical reactions (IR) in trabecular and compact bone, as well as isolated articular cartilages and growth plates of femurs were analyzed. The intensity of the immunoreaction (IR) of osteocalcin (OC), osteoprotegerin (OPG), tissue inhibitor of metalloproteinases 2 (TIMP-2), bone morphogenetic protein 2 (BMP-2), and nesfatin-1 was determined, and IR-positive cells were counted in each area of the femur. The quantitative analysis of the intensity of OC IR in growth plate cartilage and trabecular bone showed the highest values after fundectomy in comparison to the other treatments. Moreover, fundectomy increased the intensity of BMP-2 IR in articular cartilage, growth plate cartilage, and trabecular bone. The intensity of OPG IR in articular cartilage and compact bone showed the highest values after antrectomy. The intensity of TIMP-2 IR in the examined parts of the femur was highest in the rats subjected to antrectomy. The intensity of expression of nesfatin-1 IR was highest in articular and growth plate cartilages for rats subjected to gastrectomy. In conclusion, surgical procedures affecting the gastrointestinal tract, such as antrectomy, fundectomy, and partial gastrectomy, can have significant effects on bone metabolism. Our study on a rat model demonstrated varying impacts on bone homeostasis, with different surgeries leading to alterations in the expression of key regulatory proteins involved in bone remodeling.

The influence of immediate intraoperative loading with a splinting component on supporting tissues during a one-stage implant.

Aim: To study the specifics of the impact of immediate intraoperative loading with a splinting component on supporting tissues during a one-stage implantation protocol. Materials and Methods: In the course of the study, orthopedic treatment was carried out for 55 patients aged 29 to 60 years. The following were performed: cone-beam computed tomography, software planning and intraoral scanning with an optical scanner, one-stage implantation protocol, assessment of implant stability with the Osstell ISQ device, microcirculation study in the peri-implant area using laser Doppler flowmetry (LDF). Results: It was established that around loaded implants there is an increase in blood flow and vasomotor activity of the microcirculatory channel of the supporting tissues, an increase in the volume of bone tissue and an increase in torque, which is the optimal forecast for the acceleration of the pace of osseointegration. Conclusions: The use of a splinting component during immediate intraoperative functional masticatory load accelerates the dynamics of bone tissue remodeling processes around the implant, which is an optimal prediction of osseointegration rates in various dental implantation protocols and is consistent with high values of the implant stability coefficient.

HISTOMORPHOMETRIC ASSESSMENT OF CHANGES THE STRUCTURAL COMPONENTS OF THE BONE IN RATS WITH CHRONIC CHOLESTASIS WITH CORRECTION OF THE COMPLEX FROM HEPATOPROTECTOR AND SORBENT

Problem. The disruption of the gastric duct in cholestasis causes insufficient absorption in the small intestine of macro- and microelements and fat-rich vitamins (A, D, E, K), which are necessary for healthy processes, and remodeling of bone tissue. To reduce pathological changes in bone tissue diseases of the hepatobiliary system in rats statement in cholestasis, need a comprehensive approach [6]. In the core of the preventive complex one can see a hepatoprotector, which, due to its main components (lecithin, quercetin), possesses the liver protecting properties, as well as has anti-inflammatory and bile-diluting effects, and a sorbent. Aim. To conduct a histomorphometric research of the femur in rats with chronic cholestasis and evaluate the effectiveness of the prophylactic complex. Methods. The follow-up study was carried out on male rats, divided into three groups: 1st group – intact, 2nd group – rats with simulated chronic cholestasis, 3rd group – rats, who, in parallel with the development of chronic cholestasis pathology, carried out prevention. Cholestasis in rats was modeled by ligation of the biliary duct under thiopental anesthesia [9]. A hepatoprotector at a dose of 500 mg/kg and a sorbent at a dose of 1 g/kg were administered to group 3 of the animals once over a period of 4 months. Histological analysis and photography of sections of the stegnus cyst were carried out using an additional light microscope and a camera for an Olympus LC30 microscope (Japan). Morphometric studies of rat femur were carried out using the following parameters: volume (%) of the articular epiphyseal cartilage, volume (%) of the cartilage, volume (%) of the cerebrum and the number of osteoblasts per the particular area. The main results. Certain histological changes in the epiphysis of the femoral bone were found in rats with chronic cholestasis, namely, noticeable delamination of the periosteum was noted. In the deep layers of the cartilage, a decrease in the number of isogenic groups was noted, in addition, they contained a smaller number of chondrocytes. Desolation of individual lacunae, a decrease in the number of osteoblasts, and thinning of bone trabeculae were also observed, indicating certain pathological changes in bone tissue. Analysis of the morphometric parameters of the femur in rats with chronic cholestasis revealed a decrease in the specific volume of the cartilage of the articular surfaces by 25.8%, a decrease in the specific volume of the bone marrow and the number of osteoblasts by 14.4% and 39.4%, respectively, and as well as an increase of 33.1% in the specific volume of bone beams in relation to the control group. The introduction of the prophylactic complex contributed to a significant increase in the specific volume of the cartilage of the articular surfaces – by 17.2%, the specific volume of bone marrow by 42.9%, the average number of osteoblasts by 34.9%, and a decrease in the specific volume of bone beams by 31 .7% relative to the group of animals with chronic cholestasis. That is, the use of a prophylactic complex, which consisted of a hepatoprotector and a sorbent, effectively eliminated pathological changes in bone tissue that arose against the background of the development of chronic cholestasis. Conclusions. The formation of chronic cholestasis leads to pathological changes in the cartilaginous tissue of the epiphysis of the femur of the animals under study, and it itself changes the volume of cartilage of the subglobular surfaces and causes destruction of the main components in bone tissue (reduces the volume of bone marrow and the number of osteoblasts at the background of the growth the volume of bone beams). The effectiveness of prophylactic in the elimination of pathological changes in bone tissue at the background of chronic cholestasis has manifested itself as a hepatoprotective, antioxidant, anti-inflammatory and anti-inflammatory hepatoprotector and those combined with a sorbent.

Microarchitectonics and histomorphometric parameters of bone tissue during remodeling

The article shows and statistically substantiates thepeculiarities of remodeling and structure of cortical andmedullary bone tissue in two age groups (160- and 225days) of laying hens before and during egg-laying. Theaim of the study was to analyze the structural organization of bone tissue in different states of performance.The material for the study was the ulnae of the forearmof laying hens of two experimental groups. Histological studies: fixed in a 10% solution of neutral formalin,decalcified in Wilenson's fluid, dehydrated in alcoholsof increasing concentration, embedded in paraffin, prepared transverse sections from the middle third of thediaphysis, stained by Frankel, Hart, Malory, hematoxylin and eosin. Microscopy and morphometric studies were performed using an Axiolar plus microscope(Carl Zeiss), photographs were taken and measuredusing a Sigeta MDC-200 video camera (eyepiece x10,lenses x25/0.50, x40/0.65, 100/0.25) integrated with anAxiolar plus personal computer (Carl Zeiss). Statisticalprocessing of digital material was performed by Student's t-test. Changes in the structure of cortical bonetissue during the study period are associated with physiological remodeling. This is evidenced by the presenceof cementing lines of individual osteons, semi-osteonsand Haversian canals with an enlarged diameter. Theabsence or insignificant development of the insertionsystem of the forming bone plates indicates a low rateof physiological remodeling of the compact bone substance. The external general system of plates does notchange the structure. The internal general system ofbone plates is unevenly developed. From 160 to 225days of age, the development and accumulation ofmedullary bone tissue occurs, which is confirmed bya significant increase in the area of trabeculae by 2.8times (P3 = 0.999), a complication of their structureand a decrease in the area of intertrabecular spaces by1.7 times (P2 = 0.99). A significantly higher 3.4-fold(P1 = 0.95) volume of osteoblast nuclei at 160 days indicates their active functional activity - the formationof trabeculae of medullary bone tissue. During the period of 160 days, special attention should be paid to thebalance of the diet of laying hens to ensure the formation of a sufficient amount of high-quality medullarybone tissue. Key words: lamellar bone tissue, cortical, medullary, spongy and compact substance, restructuring,histomorphometry, laying hens.