The biocompatibility of magnesium alloyWE43containing rare earth (RE) elements in homogenized state and after deformation by equal channel angular pressing (ECAP) was evaluated using standard tests recommended for the preliminary estimation of the properties of materials intended for use in medical devices. It is known that the biodegradation of magnesium alloys is accompanied by evolution of hydrogen and changes of pH of the incubation medium, which can lead to the possibility of false negative results. Therefore, in this study were assessed the biocompatibility of WE43 samples in vitro and in vivo. In vitro studies of the blood cells response to the contact with the samples showed that WE43 in homogenized condition induces lysis of red blood cells (RBC) by2 ± 1.02%and in ECAP condition by1.7 ± 1.61%. The reduction of white blood cells (WBC) viability amounts to 43.2 ± 14.8% and 34.8 ± 20.2, respectively. To study cytoconductivity, the samples were incubated with multipotent mesenchymal cells (MSC) for 5 days. A reduction of cell survival after coincubation with homogenized alloy was by34 ± 8.1%, while no reduction was found for the ECAP-processed condition. Only faint signs of the sample surface colonization by MSC were observed. The collected in vitro data did not allow us to qualify these magnesium samples as biocompatible. In vivo WE43 samples were implanted subcutaneously to mice for two months. Pathology examination of organs of mice did not show any toxic reactions to the implants. There were no local inflammation, edema, or hemorrhage in the vicinity of an implant either. Each sample was covered with a fibrous capsule with blood vessels. The capsule was tightly adjoined to the surface of the sample. There was no evidence of gas accumulation in the surrounding tissue. These facts prove the biocompatibility of samples in vivo.
Thus, the data obtained in vitro do not allow a prediction for in vivo behavior in experiments on an animal model. Therefore, in order to adequately simulate the in vivo response to a candidate implant material on the basis of in vitro tests, it is necessary to significantly modify the in vivo testing protocols. This is especially important for the characterization of bioresorbable magnesium-based materials earmarked for use in implantable medical devices.
Funding for this research provided by the Russian Science Foundation (grant #18-45-06010) is gratefully acknowledged.