Review of experimental models for studying the effectiveness and safety of titanium implants

The use of three-dimensional titanium implants is becoming a common approach in reconstructive surgery for bone lesions. Computer modeling and selection of printing method parameters make it possible to create an individual implant design that takes into account the structural features, shape and size of the bone lesion. The safety requirements for implants made of titanium and its alloys as medical devi­ces are regulated by relevant documents (laws, government regulations, GOST), which require confirmation of the absence of harmful effects of the material on the body. The review provides generalized data from experimental studies of the safety properties and effectiveness of titanium implants, presented in electronic databases of scientific literature (PubMed, Embase, Google Scholar, Elibrary) for the period from 2015 to December 2023. The results of a study of the occurrence of general and local (in the implantation zone) reaction of the body, toxicity, activity of neutrophils and macrophages, the influence of biomaterial on surrounding soft tissues in the short and long term after implantation in experimental animals, study of blood parameters of animals confirming the absence of toxicity and good tolerability of implanted titanium structures. A conclusion is presented on the relevance of experimental models for studying physical, mechanical, biomechanical properties, compatibility, and safety. Each specific model has advantages that are advisable to use to solve certain problems in preclinical research. It was found that the largest number of studies are carried out on rabbits, followed by rats, dogs, sheep and goats. These studies have proven that the elastic modulus and strength of titanium alloy have values close to the values of these parameters of native bone. The object of the defect in experimental animals is most often the femur, less often the tibia, radius, etc. Differences in the ability and time of bone healing in animals and humans require extrapolation of the results to the reaction of the human body. Based on the results of the review, it can be said that there is a need to continue experimental studies on large animals (sheep) to be able to model large defects. In addition, it is necessary to standardize parameters that determine bone-implant contact and quantify bone ingrowth.