scholarly journals Histomorphological characteristics of bone replacement in rabbits with hydroxyapatite ceramics and Platelet-Rich Fibrin

2021 ◽  
Vol 23 (102) ◽  
pp. 43-52
Author(s):  
S. М. Shevchenko ◽  
M. V. Rublenko ◽  
N. V. Ulyanchich ◽  
P. P. Klymenko

The results of a histomorphological study of bone regenerates in rabbits after osteosubstitution with platelet-rich fibrin and its combination with hydroxyapatite granules with β-tricalcium phosphate in spongy and compact bone tissue at different periods of reparative osteogenesis are presented. Three groups of rabbits were formed. In the control group, the defects were left to heal under the blood clot. Bone lesions in the first experimental group were filled with platelet-rich fibrin, in the second – with a combination of platelet-rich fibrin and hydroxyapatite with β-tricalcium phosphate. All animals were kept in the same conditions of feeding and housing, had unlimited access to water. During the study, the rabbits were monitored clinically. The animals were taken out of the experiment on the 14th, 21st and 42nd days, samples of bone tissue were taken, they were fixed, decalcified, dehydrated in alcohols of increasing concentration and embedded in paraffin. In the presented study, it is most likely that the newly formed bone tissue is formed precisely due to osteoinduction in the experimental groups. When using granules of hydroxyapatite and β-tricalcium phosphate with platelet-rich fibrin, bone regenerate is between the composite granules and is not associated with contact with the maternal bone. Its cells appear in different places of the defect. In the spongy bone tissue on the 21st day, regeneration proceeded more fully and faster in the second experimental group, as evidenced by the significant density of cells of the osteoblastic row, the thickness of the bone trabeculae and their volume, filling the site of the defect. On the 42nd day, in the second experimental group, when using a combination of autobiomaterial and hydroxyapatite granules with β-tricalcium phosphate, the regenerate contained a significantly larger number of osteogenic cells in the thickness of the trabeculae, which indicated a more intensive course of reparative osteogenesis in comparison with the first experimental and control groups. In the compact bone on day 21, regeneration was more complete and faster in the second experimental group. On the 42nd day, according to the degree of maturity of the bone regenerate, calcium-phosphate ceramics in combination with platelet-rich fibrin optimizes reparative osteogenesis most clearly. According to the degree of intensity of the osteoregeneration process, the groups can be placed in the following sequence: control ˂PRF˂PRF+HA/β-TCP–700. According to histomorphological characteristics, the combination of hydroxyapatite with β-tricalcium phosphate and platelet-rich fibrin gives greater osteoinduction to the composite material, which is confirmed by the high cell density, namely of osteoblasts and osteocytes. The use of PRF in combination with other materials may become promising for the correction of reparative osteogenesis in conditions of limited or reduced regenerative potential of bone tissue.

Author(s):  
V. Chemerovsky

Treatments of fragmentary fractures in case of loss regenerative potential of bone tissue require usingdiff erent composite materials. Among all of them, ceramics based on synthetic hydroxyapatite and tricalcium phosphate are considered promising. The reparative osteogenesis in spongy and compact rabbit’s bone tissueusing 3 composite materials with diff erent physicochemical propertieswas studied. A reparative osteogenesiscontrolled by monitoring clinical, radiologic and macromorphologic parameters. Composite materials infl uence on the organism was studied by determining the dynamics of hematological parameters throughout the study period. To realize this scheme was formed a 3 experimental groups and one control group of rabbits. The created defects of animals of fi rst experimental group were fi lled out with GT + α-TKF-500, thedefects of second oneanimals group fi lled out with GTlKl-2, and defects ofthird oneanimals group fi lled out with GTlKg-700. The GTlKl-700materials were doped with silicon. In control animals, bone defects were allowed to heal under a blood clot. During the studies, all animals were located in the same environment conditions. A blood samples for hematological investigation was taken from the external jugular vein before anesthesia and at the 3rd, 7th, 14th, 21st and 42nd day after surgery. X-ray examination was performed on 14th, 21st, and 42nddays.The animals were removed from the experiment on 21stand 42nd days. The samples were examined by macromorphologic method. By radiologic examination was found that composite materials had osteoconductive properties except the silicondoped example which hadosteoinductive properties. The samples of compact bone tissue of 1st and 3rd experimental groups characterized by formation of punctate osteosclerosis with a compacted contour of the periosteumon the 42nd day. But the bone samples of 2nd experimental group had compacted contours of the periosteum only. However, in the cancellous bone tissue on the 42nd day in the animals of the 1st experimental group developed point osteosclerosis, which visualized as individual granules of the composite.But in the animals of 2nd group thewhite spot which was outlined shape and homogeneous structure at the defect was found. The bone samples of 3rd animals group shoved a clearly limited point osteosclerosisforming were was found ceramic granules. In case using ofGT + α-TKF-500, a strong connection of granules from the formed bone tissue and without any periosteal growthswas noted. Using GTlKl-2 places of defects were identical to not injured sites of radial bones. Using GTlKg-700 shows that bone defect is fi lled to the level of the plane of the bone surface and covered with a periosteum without visible growths. The granules of the composite are evenly distributed in the regenerate and associated with bone tissue. The analysis of hematological parameters did not reveal any fundamental diff erences, but the use of hydroxyapatite implants is not accompanied, in contrast to spontaneous reparative osteogenesis, the development of leukocytosis, which indicates a moderate course of its infl ammatory reaction. But the latter is accompanied by a platelet reaction, the most pronounced when using implants, which is probably due to the infl uence of platelet factors and is indirect evidence of early osteoblastic reaction. Key words: fractures, rabbits, erythrocytes, leukocytes, platelets, hemoglobin.


Author(s):  
T. Todosyuk

Fragmentary fractures require not only the use of complex methods of osteosynthesis, but also the replacement of the defect site with implants to optimize reparative osteogenesis. A large number of osteosubstitute materials are used, including hydroxyapatite ceramics. To enhance its osteointegration properties, microelements with osteoinductive properties are added. The aim of the work is X-ray and macromorphological evaluation of the influence of hydroxyapatite ceramics doped with germanium on reparative osteogenesis in model fractures of the femur and radius in rabbits. Model defects were formed in the radial diaphysis and femur metaphysis in rabbits with a drill with a diameter of 3 mm and 4.2 mm, respectively. Anesthesia included acepromazine, thiopenate, and lidocaine infiltration anesthesia. In the experimental group (n=12) defects were replaced by granules of hydroxyapatite ceramics doped with germanium, and in the control group (n=12) – undoped. The use of hydroxyapatite ceramics doped with germanium is accompanied by a moderate course of the inflammatory-resorptive phase of reparative osteogenesis. At the same time on the radiographs of animals of the experimental group on the 14th day the periosteal reaction is moderate, and on the 30th day it is barely noticeable with increased radiological density. In control animals after trauma to the compact bone proximal and distal to its location showed a thickened and compacted periosteum with a contrasting composite material. On the 60th day in the cancellous bone of experimental animals, the area of injury acquired an X-ray density close to normal, in the control – it remained elevated. Hydroxyapatin composite doped with germanium acquires osteoinductive properties and may be promising for the replacement of bone defects and correction of reparative osteogenesis in animals. Key words: bioceramics, germanium, bone fractures, compact and spongy bone tissue, rabbits.


Author(s):  
M. Rublenko ◽  
V. Chemerovsky ◽  
V. Vlasenko ◽  
N. Ulyanchich

Bone regeneration is one of the most complex and unique types of tissue regeneration, although quite long in time, comparatively, for example, with soft tissues, but provides the complete identity of the damaged site with normal bone. The most complex fractures are fragmentation, which can be occurs within wide range - 25-60% of the total number of all fractures. In such cases, due to the loss of contact with soft tissues, the fragments lose blood supply and regeneration, which leads to different bone size defect. This condition cause limitation of the main mechanisms of bone consolidation – endoostal and intramembrane ossification. In this regard, a strategic medical treatment is the replacement of bone defect with biological or synthetic material, which creates a site for the processes of reparative osteogenesis. The most widespread combined biocompatible materials in the various combinations of β-tricalcium phosphate and hydroxyapatite ("Maxresorb®", "Perossal®", "calc-i-oss®CRYSTAL", "easy-graft®CRYSTAL"), or composite composites based on bioactive and biogenic materials: hydroxylapatite + collagen (Biostite, Collagraft, Avitene, Collola, Hapkol, Collapan, MP Composite); hydroxylapatite + tricalcium phosphate + collagen ("Hydroxyapol", "Collapolum"); hydroxylapatite + collagen + sulfated glycosaminoglycans ("Biomatrix", "Osteomatrix", "Bioimplant"). Unfortunately, in veterinary medicine osteotropic materials developed for humane medicine are used only. Recently, a separate group of biocompatible composites based on the combination of hydroxyapatite with β-tricalcium phosphate, doped with magnesium, sodium, potassium, zinc, copper, aluminum, strontium, silicon, germanium, in order to provide them with specific properties - antibacterial, osteoinductive, antitumor, immunomodulating, etc. However, the spectrum of biological effects of these ions on bone metabolism is extremely diverse, and therefore the use of composite ceramics doped with microelement ions requires a comprehensive clinical and experimental justification. The purpose of the study is to evaluate the osteointegration and osteoinductive properties of ceramics based on hydroxyapatite and β-tricalcium phosphate doped with silicon for model fractures of the femur in rabbits. The work is done on rabbits of Californian breed at the age of 3 months. and a weight of about 2.5 kg. To substantiate the ceramics GTlKg-2, 2 groups of 10 rabbits were formed in each, in which model bone defects were formed in the distal parts of the hip dysthymia. Animals of the experimental group defects filled with granules of ceramics. In the rabbits of the control group, the defect was left to heal under a blood clot. Animals were extracted from the experiment at the 21st and 42nd day. X-ray and histomorphological studies were performed. On the 21st day of reparative osteogenesis, rabbits of all groups fully rested on the injured limb, signs of inflammatory reaction were absent in the experimental group, and the control marked the pronounced seal of the periosteum across the entire surface of the femur. It should be noted that hydroxyapatite ceramics does not possess x-ray contrast properties. On the 42nd day of regeneration of rabbits both groups fully rested on injured limb, signs of inflammatory reaction of soft tissues in the area of injury were absent. Radiologically, in animals of the experimental group in the place of bone defect, spot osteosclerosis was detected in the form of a clearly defined white heel, opposite to which the contour of the periosteum was sealed. At the same time, on the control X-rays, along with a well-defined, but more elongated septum of the periodontal, revealed a bone marrow panossus at the site of the injury, with a clearly defined extension of the eclipse. Substantially complemented macromorphological picture of bone biopsy. In particular, in the case of replacement of bone defect GTlKg-2, at the 21st day in the traumatic areas a limited and moderate periosteal reaction was noted. Along with this, in control animals, in this period, it was not completely replaced by fibrous cartilaginous tissue, as evidenced by its craterial appearance. Histologically, in the control animals, the bone defect formed a cartilage tissue along the periphery, and the bone beams, which were at a certain distance from the place of the defect, were at the stage of resorption. In the case of its replacement granules GTlKg-2 formed bone-ceramic regenerate, that is, the intervals between the granules are filled with bone tissue. The obtained results give grounds to consider that GTlKg-2 contributes to the formation of bone tissue due to its osteointegration and osteoinductive properties. Key words: reparative osteogenesis, osteointegration, osteocytes, osteoblasts, hydroxyapatite composite with β-tricalcium phosphate, doped with silicon.


Author(s):  
M. Rublenko ◽  
V. Chemerovskіy ◽  
V. Vlasenko ◽  
N. Ulyanchich ◽  
P. Klimenko

Metal structures for osteosynthesis available in veterinary orthopedics are not able to compensate for the lost elements of bone tissue in complex splinter fractures. It is prompt the use of hydroxyappatite materials that replaced bone defects for maintenance of osteoconductive function, and ideally would combine osteointegration and osteoinductive properties. However, their influence on the biological processes of fracture consolidation which go through a number of successive stages and end with the formation of bone tissue in the fracture zone identical to the maternal, is insufficiently substantiated according to the criteria of the molecular biological phase of reparative osteogenesis. The aim of the study was to investigate the dynamics of biochemical osteotropic parameters and the level of NO using silicon-doped ceramics for fractures heeling in dogs. Materials and methods. The animals suffering of fractures that were admitted to the faculty clinic were divided into control (n=7) and experimental (n=7) groups. In both groups, extracortical osteosynthesis was performed with a support plate from an unalloyed titanium alloy. In the control group, bone defects were left to heal under spontaneous blood clot, and in the experimental group, they were replaced with ceramic based on hydroxyapatite with β-tricalciumphosphate doped with silicon (HA/β-TCP/l-Si–3).Blood samples were taken after the injury no later than the 48th day, and on the 3th, 12th, 21th, 42th and 60th days after osteosynthesis. To increase the objectivity of the biochemical analysis, we additionally formed a group of clinically healthy dogs that were admitted to the clinic for routine vaccination (n=10). It included the spectrophotometric determination of the content of NO, BALP, TRACP, Ca, P, Mg, total protein in blood serum, and fibrinogen in blood plasma. Research results. A clinical study showed that in the case of using HA/β-TCP/l-Si–3for splinter fractures, the stages of reparative osteogenesis are more optimized in time, and their consolidation occurs on average 19 days earlier than in the control group. The results of the biochemical study showed that when using HA/β-TCP/l-Si–3, it is accompanied by a peak NO value already on the third day, which is significantly higher than in the control group and indicates early angiogenesis in the research group. In terms of TRACP, the period of osteoresorption in the control group was permanent with little expressed peaks of activity. However, in the research group, the peak of TRACP activity is limited to 12 and 21 days, which is evidence of an optimized inflammatoryresorptive phase. In parallel with this, the activity of BALP increases, which indicates the consistency of the stages of reparative osteogenesis and provides an optimized and accelerated consolidation of fractures in the research group. Conclusion. The dynamics of NO, BALP and TRACP pathochemically substantiates the optimized reparative osteogenesis when using HA/β-TCP/l-Si–3 for bone defects replacement in cases of splinter fractures of tubular bones. Key words: bone markers, bone isoenzyme of alkaline phosphatase, NO, tartrate-resistant acid phosphatase, fibrinogen, calcium, phosphorus.


Author(s):  
S. Shevchenko

The results of the dynamics of the morphological parameters of the blood of a rabbit with model defects of the opening of the spongy and compact bone tissue at diff erent periods of reparative osteogenesis are presented. Formed 4 groups of rabbits. Bone lesions in the fi rst experimental group were fi lled with injectable platelet-rich fi brin, in the second - platelet-rich fi brin, in the third - a combination of platelet-rich fi brin, and hydroxyapatite with β-tricalcium phosphate.In the control group, the defects remained healed under a blood clot. All animals were in the same conditions of feeding and keeping, had unlimited access to water. During the study, rabbits were clinically observed. Blood was taken for morphological examination before surgery and on the 3rd, 7th, 14th, 21st, 42nd day. Animals were taken from the experiment on the 14th, 21st and 42nd days, an X-ray examination was carried out, bone tissue samples were taken. It was established that trauma of bone tissue leads to a number of reactions of the body aimed at restoring the damaged area. Against the background of the general picture of the obtained morphological results, the level of platelets signifi cantly changes compared to the physiological norm, while the number of red blood cells and white blood cells does not go beyond it. There is a slight increase in hemoglobin levels, especially in the experimental groups on the twenty-fi rst and forty-second day. Signifi cant changes in the number of red blood cells, white blood cells, platelets and hemoglobin concentration in the experimental groups were noted compared with the control group at diff erent periods of reparative osteogenesis.The use of various types of platelet concentrates aff ects the overall reaction of the body. On radiographs of the radial bones (compact bone tissue) on the twenty-fi rst day in the second and third experimental groups, where fi brin enriched with platelets and its combination with hydroxyapatite materials with β-tricalcium phosphate were used to replace bone defects, the infl ammatory reaction was manifested to a lesser extent. There was no signifi cant formation of bone callus compared with the fi rst, in which model defects were fi lled with injectable platelet-rich fi brin and the control group. Each of the types of platelet concentrates and their combination with hydroxyapatite ceramics have a diff erent eff ect on the restoration of bone defects and is accompanied by the appearance of a number of reactions, both local and general. According to the degree of intensity of this process, they can be placed in the following sequence: i-PRF ˂ PRF ˂ PRF+GT. Macromorphologically and radiologically signifi cant diff erences were not detected for diff erent types of bone tissue due to the use of each of the substances that concentrates platelets. The combination of hydroxyapatite granules with β-tricalcium phosphate and platelet-rich fi brin proved to be the best option for repairing the damaged area. Its use provides a signifi cantly smaller manifestation of the local infl ammatory reaction and causes the formation of optimal bone marrow. Key words: PRF, i-PRF, granules, centrifuges, growth factors, bone marrow.


2021 ◽  
pp. 194338752110483
Author(s):  
Jonathan Ribeiro da Silva ◽  
Maria Cristina de Moraes Balbas ◽  
Caroline Águeda Corrêa ◽  
Manuella Zanela ◽  
Roberta Okamoto ◽  
...  

Objective: To evaluate the effects of inorganic bovine bone graft (Lumina Bone, Criteria, Brazil) and beta-tricalcium phosphate (β-TCP) graft (ChronOS, Synthes, Brazil) in rats with the risk of developing post-extraction medication-related osteonecrosis of the jaw (MRONJ). Methods: Eighteen male Wistar rats weighing 350 to 450 g were induced to develop MRONJ using zoledronic acid for 5 weeks. In the sixth week, the right maxillary first molar was extracted. The animals in Group I (G1) did not receive bone grafts after tooth extraction, while Group II (G2) animals received inorganic bovine bone grafts, and Group III (G3) animals received beta-tricalcium phosphate (β-TCP) grafts. Clinical evaluation and histomorphometric and immunohistochemical analyses were performed. ANOVA and Tukey’s statistical tests were used and a level of significance was considered to be 5%. Results: In the clinical evaluation, animals from G2 and G3 did not present clinical manifestations of osteonecrosis, unlike the control group (G1) animals, which presented necrotic bone tissue exposure in all samples. In the histomorphometric evaluation, animals in G3 showed greater formation of bone tissue (66%) and less formation of bone lacuna (18%) than animals in G1 (58%/32%) and in G2 (59%/27%) ( P < 0.05). Moderate (++) immunostaining was observed in G2 and G3 for RANKL, TRAP, and OC, while G1 showed moderate (++) labeling for OC and mild (+) immunostaining for TRAP and RANKL. Conclusions: Greater formation of bone tissue and fewer bone lacunae were found in animals treated with β-TCP. In clinical evaluation, bone graft groups presented with the clinical manifestation of MRONJ and showed higher intensity of immunostaining for TRAP and RANKL. Despite the limitations of experimental animal studies, the results of this work may assist in the development of future clinical research for the prevention of MRONJ.


2018 ◽  
Vol 62 (3) ◽  
pp. 385-394 ◽  
Author(s):  
Hadi Eftekhari ◽  
Alireza Jahandideh ◽  
Ahmad Asghari ◽  
Abolfazl Akbarzadeh ◽  
Saeed Hesaraki

AbstractIntroductionIn recent years, the use of bone scaffolds as bone tissue substitutes, especially the use of such as hydroxyapatite and tricalcium phosphate, has been very popular. Today, the use of modern engineering techniques and advances in nanotechnology have expanded the use of nanomaterials as bone scaffolds for bone tissue applications.Material and MethodsThis study was performed on 60 adult male New Zealand rabbits divided into four experimental groups: the control group without any treatment, the second group receiving hydroxyapatite, the third group treated with β-tricalcium phosphate, and the fourth group receiving nanocomposite polycaprolactone (PCL) scaffold. In a surgical procedure, a defect 6 mm in diameter was made in a hind limb femur. Four indexes were used to assess histopathology, which were union index, spongiosa index, cortex index, and bone marrow.ResultsThe results showed that nanocomposite PCL and control groups always had the respective highest and lowest values among all the groups at all time intervals. The histopathological assessment demonstrated that the quantity of newly formed lamellar bone in the nanocomposite PCL group was higher than in other groups.ConclusionAll these data suggest that PCL had positive effects on the bone healing process, which could have great potential in tissue engineering and clinical applications.


2016 ◽  
Vol 721 ◽  
pp. 224-228
Author(s):  
Girts Salms ◽  
Vladislavs Ananjevs ◽  
Vladimirs Kasyanovs ◽  
Andrejs Skagers ◽  
Ilze Salma ◽  
...  

Investigation of biomechanical properties of the rabbit bone tissue from a corner of the lower jaw was done. Experimental osteoporosis was induced by ovariectomy and following injections of methylprednisolone. The defects in the greater trochanter region was created and filled with granules of a hydroxyapatite and tricalcium phosphate (HAP/TCP 30/70) or HAP/TCP 30/70 together with 5% strontium ranelate. After 3 month animals were euthanased, squared samples have been cut out from a corner of the lower jaw and tested on a bend. Results of research show, that the corner of a lower jaw in rabbit becomes more rigid after filling of defects in the greater trochanter region with granules of a hydroxyapatite and tricalcium phosphate (HAP/TCP 30/70) or granules together with strontium ranelate. The ultimate strain for the bone tissue in the 2nd and 3rd group is less, than for control group. Thus, local uses calcium – phosphatic bioceramic material around the greater trochanter region improves biomechanical parameters of a bone tissue in the lower jaw of animals.


2021 ◽  
Vol 23 (102) ◽  
pp. 78-86
Author(s):  
T. P. Todosiuk ◽  
M. V. Rublenko ◽  
V. M. Vlasenko

Bone tissue has powerful regenerative properties, thanks to which, with stable fixation, quite large amounts of skeletal bone damage can be successfully repaired. However, in the case of fragmentary fractures, the use of osteosynthesis methods alone does not always ensure the optimal course of reparative regeneration, as its regenerative potential is lost. Therefore, there is a need to replace post-traumatic bone defects and stimulate reparative osteogenesis. For this purpose, doped or doped with various elements (Ge, Si, Zn, Ag, Cu) composite materials. The aim of the study was to investigate the dynamics of hematological parameters in rabbits for osteosubstitution by hydroxyapatite ceramics doped with germanium and in combination with a blood clotting activator. Model defects were formed in the radial diaphysis and femur metaphysis in rabbits with a 3 mm and 4.2 mm diameter drill bit, respectively. Anesthesia included acepromazine, thiopenate, and lidocaine infiltration anesthesia. Animals of the first experimental group (n = 12) were replaced by defects with granules of hydroxyapatite ceramics doped with germanium (HTGe), the second (n = 12) – hydroxyapatite ceramics doped with germanium with blood coagulation activator (HTGe + a), the third – (n = 12). hydroxyapatite α + β with active (α + β + a), and control – granules of undoped ceramics (HT). On day 7, animals of all groups had minor post-traumatic erythrocytopenia and oligochromemia. There was also a gradual increase in the content of leukocytes in the blood with a peak on the 14th day, which in the group HTGe + a lasted until the 30th day. The increase in the number of leukocytes and their peak values occurred within the physiological norm and only approached its upper limit. In most groups there was a pronounced thrombocytosis during the first 14 days with normalization to the 30th day, but in the 2nd experimental group the number of platelets returned to normal only on the 60th day. Changes in most integral hematological indices, which reflect the relationship between blood cell populations, are characteristic of the inflammatory-resorptive phase of reparative osteogenesis. The dynamics of hematological parameters indicates the absence of a pronounced reaction of the body to the implantation of hydroxyapatite composite doped with germanium. The combination of hydroxyapatite ceramics doped with germanium with coagulation activator eliminates post-traumatic oligochromemia and erythrocytopenia and significantly increases the level of hematological integral indices, which indicates a more intensive course of inflammatory-resorptive clinical resorptive aparation phase.


2020 ◽  
Vol 11 (2) ◽  
pp. 289-293
Author(s):  
M. A. Rybalka ◽  
L. M. Stepchenko ◽  
O. O. Shuleshko ◽  
L. V. Zhorina

Humic acids are characterized by chelating properties due to which they are able to influence the mineral metabolism in animals. Rabbits have species-specific characteristics of mineral metabolism, which distinguishes them from most species of mammals. For the experiment, 16 rabbits of 45-day-old of Hyplus breed were divided into the experimental and control group of 8 rabbits in each. The animals were 15 days in the preparatory period. The rabbits of the experimental group received humic acid additive individually with water in the amount of 5 mg/kg, the rabbits of the control group received pure water in the same amount. The ability of humic acid additive to increase the content of calcium, ionized calcium, iron, to correct the content of copper and zinc, and also to increase the activity of alkaline phosphatase in the blood serum of rabbits of the experimental group has been proved. We observed the early effect of the humic acid additive on increasing the content of iron and calcium ionized and a later effect on the activity of alkaline phosphatase and an increase in the content of copper in the blood serum. The influence of humic acid additive on the distribution of calcium, phosphorus, manganese, copper and zinc in bone tissue is determined. According to a histological study, there was a significant increase in the number of layers of osteons and osteoblasts in the bone tissue of the femur, an increase in the number of osteons and osteoblasts in the bone tissue of the sternum and an increase in the number of columns of chondrocytes and an increase in the number of chondrocytes in the column in the cartilaginous tissue of the sternum. The results of a histological study of bone tissue, together with an increase in structural macroelements in it and redistribution of osteotropic trace elements in the blood and bone tissue suggest the possibility of using a humic acid additive to intensify the growth and mineralization of bone tissue, which can improve the state of bone tissue of rabbits in the postnatal period ontogenesis.


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