PATHOGENETIC RATIONALE FOR THE INFLUENCE OF MULTINUCLEATED GIANT CELLS ON THE FORMATION OF PERI-IMPLANTATION FIBROSIS USING MESH PROSTHESIS IN SURGICAL PRACTICE

Abstract

The aim of this study was to investigate the pathogenetic role, morphofunctional characteristics, and dynamics of changes in multinucleated giant cells in the formation of the peri-implantation capsule.

Material and methods. The experimental study was conducted on male rats weighing 200–250 grams, divided into 3 groups based on the time of removal — on days 7, 14, and 30. The mesh endoprosthesis “Esfil”, measuring 1.5 × 1.5 cm, was implanted under sterile conditions under general anesthesia into a subcutaneous pocket in the interscapular region, and the wound was sutured.

Results. The main participants in matrix remodeling are activated macrophages, giant multinucleated cells, fibroblasts, lymphocytes, and mast cells. At the same time, M1 phenotype macrophages transform into an M2 phenotype that produces profibrogenic mediators. Under the influence of cytokines IL 4 and IL 13, M2 macrophages fuse and form giant multinucleated cells, which in turn influence fibro  and angiogenesis occurring in the peri implant area. Under experimental conditions, on the 7th day after implantation of the “Esfil” endoprosthesis, isolated giant multinucleated cells of small size (25–40 μm) are visualized in the field of view on the endoprosthesis threads; their nuclei, numbering from 3 to 6, are located in the center of the cell. By the 14th day, the giant multinucleated cells reach the peak of their morphofunctional activity. The shape of the cells changes: from oval, they become flattened; giant multinucleated cells elongate along the surface of the monofilaments; their size reaches 100 μm, the number of nuclei is up to 15, and they are located along the periphery of the cell. The density of giant multinucleated cells increases to 4–5 per field of view. By the 30th day of the experiment, against the backdrop of a 1.5 fold reduction in the size of giant multinucleated cells and their number dropping to 2–3 per field of view, a predominantly eccentric arrangement of nuclei is observed, and their number does not exceed 12 per giant multinucleated cell.

Conclusion. The observed morphological activity of giant multinucleated cells on day 14 indirectly indicates the maximum level of secretion of transforming growth factor and platelet derived growth factor, as well as the stimulation of fibroblasts to produce collagen, which coincides with the formation of a clearly visible capsule. By day 30, the functional activity of giant multinucleated cells subsides, and a mature fibrous capsule is observed in the periprosthetic area, ensuring full integration of the endoprosthesis into the tissue. Understanding the mechanisms by which giant multinucleated cells influence fibrogenesis and angiogenesis opens up prospects for targeted correction of excessive fibrosis and improving the biointegration of implants.

Financing: The authors declared that there was no source of financing.