Abstract

Relevance: In recent decades, much attention has been paid to the use of experimental models of various pathological processes to determine the main mechanisms of their pathogenesis and to study the effect of new pharmacotherapeutic agents. Sufficiently complex models include models of traumatic lesions of the bone apparatus and, especially, those that are accompanied by a significant reaction of nervous tissue and its structures, for example, traumatic brain injury (TBI). We created a rabbit iliac bone injury model without damage to the bone marrow structures and carried out experimental therapy of the locally affected area using the “Syntekistka” biocomposite with dynamic morphological control of the injury state during up to 12 months of observation and established the positive effect of surgical treatment with the use of hydroapatite biocomposite.

Aim: In order to determine the pathophysiological basis of effective experimental therapy of bone trauma in animals and repair mechanisms, it seemed appropriate to find out the state of growth factors and pro-inflammatory cytokines based on their quantitative content in the blood serum of rabbits.

Material and methods: Research of pro-inflammatory cytokines according to their quantitative content in the blood serum of rabbits at the research points: “0” – the baseline before the start of the experiment before the start of the experiment; “1” – 1 month after the injury without using a biocomposite; “2” – 1 month after the injury with the use of a biocomposite; “3” – after six months without using biocomposite; “4” – after six months with the use of biocomposite. Simulation of traumatic damage to the iliac bone in rabbits, as well as the treatment regimen after the injury, was carried out as previously described. Growth factors and pro-inflammatory cytokines were studied at the indicated sampling points from 0-4. Blood was obtained from the ear vein at a fixed time. The serum content of transforming growth factor (TGF-1β), fibroblast growth factor, interleukins-6 and 1β, immunoglobulin class G was studied. The study was conducted on two groups of rabbits, 7 in each. The animals were bled from the ear vein before modelling the iliac bone. Serum was obtained and stored in a refrigerator at – 200C for no more than 3 months. Trauma modeling was performed according to recommendations. In the control group, the treatment was carried out by fixing parts of the bone with a metal plate followed by fixing the limb. Surgical treatment with the use of BCS “Sintekost” was performed according to recommendations. All the indicated factors of immunity were determined by the immunoenzymatic method [3] using the Stat Fax 2100 analyzer (US) and sets of reagents from «Hema» (Ukraine), «Elabscience» (USA), «Euroimmun» (Belgium). We followed the recommendations of the statistical programs Biostat-6 and Win-Pepi.

Results and discussion: Almost all investigated immune factors underwent the same profile of changes: increased levels of both growth factors and pro-inflammatory interleukins. The so-called “normalization” of the studied factors content factors was noticeable during the observation period of six months, mainly in the group of animals where a biocomposite material of the “Syntekistka”. type was applied locally in the trauma zone. As for the content of immunoglobulin class G in blood serum, no significant deviations compared to the starting level (“0”) were detected (there were none).

Analyzing experimentally obtained data and facts indicated in literary sources on the problem of using biocomposite materials with a conventional designation such as “Syntekistka”. for bone repair in case of different localization injuries, the following generalizing assumptions can be made:

– the use of hydroapatite-based biocomposite materials in the surgical treatment of bone injuries is more pathogenetically justified method than metal osteosynthesis;

– the use of the biocomposite is accompanied by systemic changes in the cytokine profile, in particular, TGF-1β, fibroblast growth factor, IL-6, interleukin-1β and the approach of these indicators to the normal level, which was noted in the group with the use of the biocomposite at the end of the observation period in more effective trauma therapy and indicates the pathogenetic nature of this approach to the treatment of bone injuries;

– a further thorough study of the state of both systemic and, especially, local (in the wound) immunity is necessary before carrying out the treatment process with the use of biocomposite materials “Syntekistka” type.

Conclusions: Considering the peculiarities of natural reparation of damaged bone tissue, the use of “Syntekost” type biocomposite is a promising method for ensuring full regeneration in case of bone injuries.

Key words: bone injuries, cytokines, growth factors, BCP “Syntekistka”.