A REVIEW OF ANIMAL MODELS FOR BONE FRACTURE NONUNION AND THEIR ROLE IN STUDYING BIOLOGICAL THERAPY EFFICACY

The bone healing impairment, such as non-union fractures after injuries of long bones, lead to loss of working capacity and result in significant financial costs, which emphasizes the socioeconomic significance of the problem. However, it is not known which method of modeling the non-union bone fractures is more optimal for further research into the effectiveness of biological therapy aimed at treating bone healing impairment. For a detailed study of methods of non-union fracture treatment of, it is necessary to determine the developed animal models. The objective was to analyze the existing animal models of fracture nonunion in long bones in vivo and to consider the possibility of their further use to evaluate the effectiveness of the use of modern biotechnologies for the in the management of fracture nonunion. It was found that the majority of developed animal models of atrophic long bone non-union were created using small animals, namely rats, mice, and rabbits. A more common method of modeling bone non-union is performing an osteotomy with the formation of a defect of different widths between the bone fragments and subsequent removal of the periosteum proximal and distal to the osteotomy site; damage to the endosteum or removal of bone marrow. Also, in such animal models, researchers use a silicone spacer, a polysulfone plate, or a latex-silicone foil to physically prevent fracture union. In these animal models, studies using mesenchymal stromal cells, platelet-rich plasma or bone morphogenetic protein-2 (BMP-2) have already been conducted for the management of non-union bone fractures. At the same time, the clinical results of the application of various biological therapies are ambiguous, which determines the conduct of further experimental studies, in particular, in vivo. However, there are disagreements about which in vivo modeling methods give a reproducible result and prevent bone union, which determines the need for further analysis of existing modeling tools for  conducting research in this direction.