Dynamics of acute-phase and endothelial reactions and immune complex formation during bone replacement with germanium-doped calcium-phosphate ceramics of bone fragment fractures in dogs

Abstract

Bone defects that occur with fragment fractures lead to an increase in the number of postoperative complications. Therefore, to restore the structure and function of the bone, there is a need for bone replacement, in particular doped calcium-phosphate ceramics. The purpose of the work is the biochemical assessment of acute-phase and endothelial reactions and immune complex formation during bone replacement with germanium-doped calcium-phosphate ceramics of bone fragment fractures in dogs. Dogs with fragment fractures of long tubular bones and plate osteosynthesis were included in the study. In the experimental group (n = 10), bone defects were replaced with germanium-doped calcium-phosphate ceramics (HА/β-TCP/l-Gе-700), in the control group (n = 10) – unalloyed (HА/β-TCP-700). Blood samples were taken after the injury and on the 3rd, 7th, 14th, 30th, and 60th days after osteosynthesis. Partial recovery of limb function in the experimental group was faster by 1.3 times (P < 0.001) and full by 1.2 times (P < 0.01) compared to the control. On the 60th day, in experimental animals, the defect was filled with a regenerate of high X-ray density without a periosteal reaction, while in the control animals, the bone regenerate did not have sufficient density with a significant periosteal reaction. In both groups, total protein and albumin content varied within the normal range. The activity of protein C on the 3rd day in the experimental group was 1.3 times higher (Р ˂ 0.001), and on the 7th day, it was twice as high (P ˂ 0.001) compared to the control group with normalization by the 14th day. The concentration of ceruloplasmin from the 7th day in the control animals was 1.1 times higher (Р ˂ 0.001) than in the experimental animals, with normalization in the latter by the 60th day. The level of small molecular circulating immune complexes (CIC) after the injury increased by 1.1 times (Р ˂ 0.001) and reached a peak in the control and experimental groups on the 14th day, with an increase in indicators by 2.1 and 1.4 times (Р ˂ 0.001), respectively, with normalization in the experimental group on the 60th day. The level of nitric oxide (NO) in the control group increased from the 7th to the 60th day, with a peak on the 30th day, and in the experimental group – from the 3rd to the 30th, with a peak on the seventh day. Osteoreplacement of fragment fractures of long tubular bones in dogs with calcium-phosphate ceramics doped with germanium is accompanied by a moderate level of the acute phase reaction and immune complex formation, an increase in the endothelial reaction and the anticoagulant potential of the blood, which contributes to a decrease in the intensity of the inflammatory-resorptive stage of reparative osteogenesis and an increase in its proliferative phase, which, respectively, accelerates the consolidation of fractures.

Keywords

• reparative osteogenesis; bioactive ceramics; nitric oxide; metal ions; immune complexes; protein c.