In this article, a comparative analysis of two experimental methods for treatment of chronic parodontitis was carried out, using a locally applied composition of silicon glycerohydrogel — peptide, and local injections of “Polyoxidonium” drug. The aim of this study was to compare efficiency of the two experimental methods for treatment of chronic periodontitis. Materials and methods: Using the facilities at the Institute of Immunology and Physiology (Yekaterinburg), a model of chronic inflammation of periodontal tissues was developed in Wistar rats, further treated by two experimental methods, i.e., (1) applying a composition containing organosilicon glycerohydrogel and a synthetic peptide, or (2) injections of “Polyoxidonium” drug directly into the foci of inflammation. Subsequently, a comparative evaluation of their efficiency was performed, including comparisons with control groups. The latters were treated by topical use of organosilicon glycerohydrogel (Group 1), and the local application of “Metrogyl Denta” gel (Group 2). Upon completion of the treatment, clinical and histological data were evaluated and compared. As based on the data obtained, we have found that all these drugs exerted favorable effect on the tissue regeneration, and led to reduced intensity of inflammatory processes. We have revealed also that the organosilicon glycerohydrogel — peptide composition provided a faster effect, due to the special characteristics of its components. The hydrogel, which has transcutaneous activity and plays a role of conductor substance, promotes faster penetration of the peptide into the tissues, thus allowing the peptide substance for more pronounced, complex antimicrobial and regenerative effect upon various pathogenetic components of chronic perirodontitis. If compared with the groups treated by glycerohydrogel silicon and “Polyoxidonium”, the terms of clinical improvement in the glycerohydrogel-peptide group were found to be increased by 57%, and appropriate indexes in the group treated with “Metrogyl Denta” improved by about 15%. The results of histological examination have confirmed normalization of the local tissue structure, as well as decreased inflammatory response observed for all the groups. Of particular interest, regeneration terms in the glycerohydrogel-peptide group were shorter (16 to 20 days) than in other groups (from 20 days), thus suggesting a more pronounced effect of this composition when compared to other treatments. Due to the presence of antimicrobial peptides in formulation of the glycerohydrogel-peptide composition, both pathogenetic and etiological links of the disease are affected, thus being important for development of integral approach to the treatment of chronic periodontitis.

Since the jawbone tissue is injured at the stage of metal dental implant introduction, the problem of inflammatory complication development leading to a breakdown in osseointegration remains relevant. Of interest are the immunological mechanisms of inflammatory process development during the emission of metal nanoparticles, as well as the mechanisms of its subsidence after the removal of a metal object. Microscopic and elemental analysis of the bone tissue of the Wistar rat lower jaw after artificial traumatization was carried out. During the experiment, the situation of presence of a metal foreign body in the bone bed was simulated. An insulin needle was injected into the connective tissue of the lower jaw, followed by its removal after seven days. Microscopic analysis of bone tissue was performed using a Tesscan Vega 4 scanning electron microscope. The teeth alveoli cortical layer surface, connection of the jaws with a gap, stratification of the cartilaginous layer were determined at low magnification in direct projection. Using higher magnification in the direct projection there are visible dense-structural crystalline inclusions, foci of necrosis in the area of junctions of the jaws alveolar processes. The elemental composition of bone tissue was obtained by atomic emission spectroscopy by iCAP 6300 Duo. In the test sample, the quantitative ratio of calcium and phosphorus was 1.68, which slightly exceeds the optimal value of 1.67. An upward change in this ratio indicates a decrease in phosphorus level, which can be interpreted as local osteoporosis. In addition, the following elements were found: Bi, Ga, Pb, Ti, Zn in the amount of 0.03-0.06 mass percent. The list of these elements corresponds to the chemical composition of an insulin needle, indicating the penetration of metal particles into bone bed tissues. The emission of nanoparticles and their subsequent association to micro- and submicron sizes, their persistence, as well as biocorrosion in areas of active bone formation can be a trigger for the development of an aseptic inflammatory process. This effect is due to both a direct damaging factor and an indirect effect through specific signal molecules produced in response to tissue damage.

Antimicrobial function of innate immunity is mediated by the low-molecular weight peptides which are active against bacteria, fungi and some viruses. The review presents data on studies of both natural and synthetic peptides regarding the features of their structure and therapeutic effect. As a rule, the molecules of such peptides are positively charged, due to amino acid radicals capable of protonation. Spatially, antimicrobial peptide molecules are arranged as -helices or -layers in separate or compound assemblies. At the same time, short molecular chains, including up to 18 amino acid residues, exist as a linear or cyclic forms, remaining at the level of primary spatial structure. Natural antimicrobial peptides are predominantly produced by neutrophilic granulocytes and macrophages, as well as epithelial cells of the barrier organs. Three families of natural antimicrobial peptides have been most studied: defensins, cathelicidins, and histatins. Defensins are active against Gram-positive and Gram-negative bacteria, viruses and fungi, having anti-inflammatory and immunomodulatory activity. Cathelicidins are chemoattractants and exert antibacterial, immunomodulatory, wound healing, antitumor effects, potentially contributing to the development of autoimmune diseases. Histatins have a pronounced fungicidal effect and prevent the formation of bacterial biofilms. A detailed study on the structure and principles of action of natural antimicrobial peptides made it possible to apply this information for the in vitro synthesis of peptides thus making it possible to create multipurpose drugs based on them. E.g., synthetic peptides WR12 and D-IK8 ensure the delivery of antibiotics to infected or tumor cells, due to permeabilization of cellular membranes. At the same time, a synthetic peptide, acipensin 1, is capable of penetrating into human tumor cells without damaging them. The immunomodulatory peptide glutoxim is effectively used in anti-tuberculosis therapy. ZP2 peptide, the functional site of granulocyte-macrophage colony-stimulating factor is effective against Gram-negative bacteria (K. pneumoniae, P. aeruginosa and A. baumannii) as well as EpsteinBarr virus. Thymic immunoregulatory peptides bestim, hepon, thymogen and imunofan are inducers of endogenous - and -interferon production, inhibit the development of malignant neoplasms, and possess anti-inflammatory activity. Gepon is used in the treatment of viral hepatitis, respiratory and opportunistic infections, croup syndrome and sexually transmitted infections (including genital herpes). Thus, the synthetic antimicrobial peptides are widely used in complex treatment regimens along with conventional antibiotics, antiviral, and antitumor drugs, thus making it possible to achieve higher therapeutic effect.

This article highlights current issues on medical treatment of chronic periodontitis. The lack of effective comprehensive approach to treatment of chronic periodontitis requires to seek for new treatment strategies, which will be based on pathogenetic features of disease development. Experimental study with Wistar rat strain was used as a model of chronic periodontitis created by inserting a 12 mm needle into the periodontal space of the lower incisor. More than 30 models of chronic periodontitis were obtained. A method of conservative therapy by using an immunomodulator (polyoxidonium) was proposed. The aim of the study was to evaluate efficacy of polyoxidonium in treatment of chronic periodontitis model. To do this, we compared efficacy of treatment with polyoxidonium and treatment with an antibacterial drug, Metrogil Denta gel. Development of model of chronic periodontitis was performed in two groups of our study. In the first group, periodontitis was treated with polyoxidonium injected into alveolar process mucosa of the lower jaw. In the second group – antibacterial gel “Metrogil Denta” was applied to the area of inflammation. Finally, clinical and histological assessment of therapeutic efficacy was performed. It was found that the main clinical parameters after immunomodulatory therapy were not inferior to those obtained after treatment with Metrogil Denta gel. During treatment, hyperemia, edema, and bleeding gums were decreased in both groups. Evaluation of clinical data after treatment with polyoxidonium suggested that improved parameters evidenced about good immune-mediated activity of the drug and need to continue further efficacy examination in treatment of inflammatory periodontal diseases. To assess the histological picture, 60 decalcified sections were examined (two per each animal, respectively). Data from control group without treatment were described previously, and were used for comparison. Histological examination confirmed ongoing healing process in all three groups. In group 1 treated with immunomodulator, pharmacological properties of polyoxidonium favorably affected regeneration of periodontal tissue, which, however, required longer period of time, more than 20 days. It proves a pronounced efficacy of polyoxidonium in treatment of inflammatory periodontal diseases, even as a standalone therapy without combining with antibacterial drugs.

Modern medicine allows us to study and develop materials and methods of restorative treatment that would be based on the immunological mechanisms of bone repair. One of the promising directions in guided bone regeneration is the use of mesenchymal stem cells. Interest in MSCs is associated with their ability to regulate the inflammatory process, and directly participate in the formation of new bone structures, thereby providing a physiological repair process. The effector impact of MSCs on the inflammatory process due to their ability to form a specific microenvironment. Low expression of MHC-II and CD80/CD86, the production of PGE2 and NO determines their low immunoconflict, and the production of TGF-b1, IDO and IL-10 has an immunomodulating effect. The ability of MSCs to differentiate into an osteogenic phenotype is accompanied with the synthesis of ALP, BSP and, subsequently, Gla-protein and OPN determine the synthesis of the extracellular matrix and its subsequent mineralization. This process is provided by the action of Runx2, which activates the differentiation of MSCs along the osteogenic pathway. These effects of MSCs were taken as the basis for the development of a new method for the treatment of bone atrophy. To accomplish the task set, a model of bone tissue atrophy and a drug containing MSCs was developed, and an experimental study was conducted to evaluate the effectiveness of the developed methodology. As the main criteria, data from clinical and laboratory studies were taken. Visual changes in the studied area were taken into account, compared with a similar area in the developed model of atrophy, the parameters of the complete blood count (CBC) were evaluated. The performed study allows us to determine the developed treatment method as capable of fully recreating the conditions of bone repair processes, taking into account the optimization of the body’s immune reactions and repair processes, without additional external influence, to obtain predictable and controllable results.