Analysis of Permissible Limits for Leachable of Trace Impurities from Bone Substitutes Containing Hydroxyapatite and Beta-Tricalcium Phosphate

A detailed analysis of the regulatory framework for the biological assessment of nanomaterials and medical devices indicates that the main factor of uncertainty in laboratory results of studies on the influence of nanostructures is biological variation due to individual and population characteristics of vital processes in the human body and is characterized by a combination of stability within the average limits of the constancy of the internal environment and dynamic fluctuations around the point of homeostasis. Objectively substantiated recommendations have been developed on the accuracy of laboratory studies when assessing the biological effects of synthetic nanostructures. A basis for assessing the accuracy is the maximum permissible values of analytical errors of quantitative research methods (measurements) of physical quantities (composition and properties of components of biological materials, analytes) in samples of biological materials. The above interpretation of LOD and LOQ is close to the "confidence interval" concept. The statement about detecting the concentration of leachable trace impurities in biofluid is always probabilistic in nature. The revealed patterns indicate that trace impurities elements have different dissolution rates and depend on the ratio of the structural components of the product/material. The study of hydroxyapatite-containing nanomaterials showed that the hydroxyapatite/beta-tricalcium phosphate ratio affects the material's dissolution rate: the higher the content of beta-tricalcium phosphate, the higher the dissolution rate. The results allow providing recommendations for reducing uncertainty in the study of hydroxyapatite and /beta-tricalcium phosphate bone substitutes, which is associated with individual reactions of the body to various environmental factors and obeys statistical laws.