Comparative Study on the Responsiveness of Different Species to Coagulation and Complement for Hemocompatibility Evaluation

Abstract

Background: According to the International Standard (ISO10993-4), a test model using human blood must be used for blood compatibility evaluation of medical devices. However, various safety investigations have reported outcomes from animal models simulating clinical conditions. Additionally, the validation of animal blood in blood compatibility assessment models is limited. In this study, the differences in the reactivity of different species to coagulation and complement, as well as the main mechanisms governing blood clot formation upon contact with medical devices, were examined. Moreover, it aimed to acquire information required to design a hemocompatibility evaluation model and interpret the results. Results: Rabbits, porcine, rhesus monkeys, and cynomolgus monkeys were exposed to one negative and two positive control substances, and variations in the partial thromboplastin time (PTT) were observed. The activity of the complement system was observed in accordance with the test method in ISO 10993-4. Although the PTT absolute values varied across animal species, the normalized PTT values—61% for rabbits, 66% for pigs, 63% for rhesus monkeys, and 65% for cynomolgus monkeys—exhibited no statistically significant differences. After reacting human and porcine sera with the material, the test model using human serum distinguished the positive and negative control candidates, whereas the test model using porcine serum could not discriminate them. Conclusions: These results suggest similar reactivity in blood coagulation across species after substance contact. However, complement system activity indicated a significant difference in reactivity between human and porcine blood. This finding will be useful in the design of a blood compatibility evaluation model for medical devices and interpretation of the results.